Background: Benveniste’s biology experiments suggested the existence of molecular-like effects without molecules (“memory of water”). In this article, it is proposed that these disputed experiments could have been the consequence of a previously unnoticed and non-conventional experimenter effect. Methods: A probabilistic modelling is built in order to describe an elementary laboratory experiment. A biological system is modelled with two possible states (“resting” and “activated”) and exposed to two experimental conditions labelled “control” and “test”, but both biologically inactive. The modelling takes into account not only the biological system, but also the experimenters. In addition, an outsider standpoint is adopted to describe the experimental situation. Results: A classical approach suggests that, after experiment completion, the “control” and “test” labels of biologically-inactive conditions should be both associated with “resting” state (i.e. no significant relationship between labels and system states). However, if the fluctuations of the biological system are also considered, a quantum-like relationship emerges and connects labels and system states (analogous to a biological “effect” without molecules). Conclusions: No hypotheses about water properties or other exotic explanations are needed to describe Benveniste’s experiments, including their unusual features. This modelling could be extended to other experimental situations in biology, medicine and psychology.

Biogenic emissions affect the urban air quality as they are ozone and SOA precursors and should be taken into account when applying photochemical pollution models. The present study presents an estimation of the magnitude of Non-Methane Volatile Organic Compounds emissions (NMVOCs) emitted by vegetation over Greece. The methodology is based on computation performed with the aid of a Geographic Information System (GIS) and theoretical equations in order to develop an emission inventory on a 6x6 spatial resolution, in a temporal resolution of 1hr covering one year (2016). For this purpose, a variety of input data was used: improved satellite land-use data, land-use specific emission potentials, foliar biomass densities, temperature and solar radiation data. Hourly, daily and annual isoprene, monoterpenes and other volatile organic compounds (OVOCs) were estimated. In the area under study, the annual biogenic emissions were estimated up to 472 kt, consisting of 46.6% isoprene, 28% monoterpenes and 25.4% OVOCs. Results delineate an annual cycle with increasing values from March to April, while maximum emissions were observed from May to September, followed by a decrease from October to January.

With the advancement of next generation sequencing in past several years, a rising number of non-coding RNAs have been found as new actors to regulate gene expression. Non-coding RNAs not only play important roles in carcinogenesis, but also affect the clinical treatment strategies. They have been proved to be deeply correlated with chemoresistance in several cancers. Ovarian cancer is the leading cause of death in gynecological malignancy, with low 5-year survival rate. Most patients are identified when they have late-stage disease. This review mainly makes a compilation of the most relevant research literature in this field with the purpose of shedding light on the relation between ncRNAs and chemoresistance in ovarian cancer.

1) Background: the budget of non-thermal energy in galaxy clusters is not well constrained, owing to the observational and theoretical difficulties in studying these diluted plasmas on large scales. 2) Method: we use recent cosmological simulations with complex physics in order to connect the emergence of non-thermal energy to the underlying evolution of gas and dark matter. 3) Results: the impact of non-thermal energy (e.g. cosmic rays, magnetic fields and turbulent motions) is found to increase in the outer region of galaxy clusters. Within numerical and theoretical uncertainties, turbulent motions dominate the budget of non-thermal energy in most of the cosmic volume. 4) Conclusion: assessing the distribution non-thermal energy in galaxy clusters is crucial to perform high-precision cosmology in the future. Constraining the level of non-thermal energy in cluster outskirts will improve our understanding of the acceleration of relativistic particles by cosmic shocks and of the origin of extragalactic magnetic fields.

In this study, we mainly focus on the behavior of an electron gas produced by argon plasma that is bounded by a moving rigid flat plate. The effects of an external magnetic field on the electrons collected with each other, with positive ions, and with neutral atoms in the plasma fluid are investigated. We used the BGK model of the Boltzmann kinetic equation, which is fundamental in the study of the gas dynamics from the continuum flow to the free-molecular regimes with Maxwellian velocity distribution functions of the various species. An exact analytical solution of the model equations for the unsteady flow is given using the moment and the traveling wave methods. The behavior of the mean velocity of electrons is illustrated, which compatible with the variation of the shear stress, viscosity coefficient, and the initial and boundary conditions. Besides, the thermodynamic prediction is investigated by applying the principles of irreversible thermodynamics and Gibbs formula. It is found that the thermodynamic variables verify the Boltzmann’s H–theorem, the principle of Le Chatelier, and the Thermodynamics Second Law for the non-equilibrium processes of the system. Qualitative agreements with previous related papers are introducing. 3-Dimensional graphics for the calculating variables are offering, and their behavior is deeply discussed.

This article develops duality principles and related convex dual formulations suitable for the local optimization of non-convex primal formulations for a large class of models in physics and engineering. The results are based on standard tools of functional analysis, calculus of variations and duality theory. In particular, we develop applications to a Ginzburg-Landau type equation.

Objective: To investigate fundamental movement skills (FMS) and physical activity differences among Hispanic and non-Hispanic White elementary school children. Materials and Methods: This study included 194 children aged between 4 and 11 in kindergarten, 2nd, and 5th grades. For evaluable participants, t-tests were used to test potential differences in fitness or movement skills. The characteristics of Hispanic and non-Hispanic White were compared using the p-value to detect statistical differences in anthropometric, FMS, and fitness characteristics. To identify any noticeable differences, the means and standard deviations of each group were compared. Results: There were significant group differences across the participants in age, height, Body Mass Index (BMI), BMI percentile, arm circumference, and waist circumference. In addition, there were significant differences between Hispanic and Non-Hispanic White in catch, run, dodge, punt, and two-hand strike (all p’s <0.05). Lastly, there were significant differences between Hispanic and Non-Hispanic White in pull-up, push-up, and sit-up (all p’s <0.05). Conclusion: Future studies should focus on decreasing obesity, increasing fitness, and FMS in elementary school children. Particularly, with Hispanic children whose FMS is negatively affected at such a young age, leading to eventual implications for their physical fitness and health in the future.

In this paper, a polyacrylic elastomer latex with butyl acrylate (BA) as the core and methyl methacrylate (MMA) copolymerized with glycidyl methacrylate (GMA) as the shell, named poly(BA-MMA-GMA) (PBMG), was synthesized by seeded emulsion polymerization. Cellulose nanocrystal (CNC) was dispersed in the polyacrylic latex to prepare PBMG/CNC dispersions with different CNC contents. The dried product was mixed with polylactic acid (PLA) to fabricate PLA/PBMG/CNC blends. The addition of PBMG and PBMG/CNC improved the mechanical properties of the PLA matrix. Differential scanning calorimetry (DSC) was used to investigate the non-isothermal crystallization kinetics. The Avrami equation modified by Jeziorny, and the Ozawa, and Mo’s equations were used to analyze the nonisothermal crystallization kinetics of PLA and its blends. Analysis of crystallization halftime of nonisothermal conditions indicated that the overall rate of crystallization increased significantly at 1 wt% content of CNC. This seemed to result from the increase of nucleation density and the acceleration of segment movement in the presence of CNC component. This phenomenon was verified by polarizing microscope observation.

Non-alcoholic fatty liver disease (NAFLD), a frequent complication of metabolic syndrome and visceral obesity, is characterized by marked accumulation of lipids in hepatocytes, accompanied by oxidant stress. In a substantial minority of cases, this progresses to steatohepatitis, which in turn can lead to life-threatening hepatic fibrosis and/or hepatocarcinogenesis. This essay analyzes the molecular biology underlying fat accumulation and oxidant stress in NAFLD, and identifies targets that can be addressed by nutraceutical or dietary measures. Nutraceuticals with potential for prevention or control of NAFLD – as suggested on theoretical grounds, and borne out by experience in rodent studies and/or clinical trials - include ferulic acid, melatonin, methylnicotinamide, tetrahydrocurcumin, nicotinamide riboside, carnosic acid, urolithin A, quercetin, high-dose biotin, citrulline, astaxanthin, long-chain omega-3 fatty acids, berberine, lipoic acid, silibinin, N-acetylcysteine, taurine, capsaicin, spermidine, spirulina, and carnitine. Some of these agents can also address the NLRP3 inflammasome activation and transforming growth factor-β signaling that play a role in driving the transition to steatohepatitis and fibrosis. In addition, soy isoflavones, via estrogen receptor-beta agonism, have anti-fibrotic potential, and supplemental glycine may blunt the contribution of Kupffer cells to the progression of NAFLD. Whole-food plant-based diets of modest protein content, owing to their impact on hormones such as fibroblast growth factor 21 and adiponectin, as well as on the obesity and metabolic syndrome underlying NAFLD, may also be protective in this syndrome. There is considerable potential for complex medical foods or nutraceutical supplementation regimens of rational design to aid prevention and control of NAFLD.

Precipitation processes are technologies commonly used in hydrometallurgical plants to recover metals or to treat wastewaters. Moreover, solid-liquid separation technologies, such as thickening or filtering, are relevant unit operations, included in the precipitation technologies. These methods are strongly dependent on the characteristics of the solid precipitates formed during the specific precipitation reaction. One of these characteristics is the particle size distribution (PSD) of the solid precipitates which are fed into a solid-liquid separation process. Therefore, PSD determination is a typical practice for the characterization of the slurries generated in a precipitation plant. Furthermore, the precipitates generated in these processes have a colloidal or aggregation behavior, depending on the operational conditions. Nevertheless, the conventional methods used to estimate PSD (e.g., laser diffraction and/or ciclosizer) have not been designed to measure particles that tend to aggregate or disaggregate, since they include external forces (e.g., centrifugal, agitation, pumping and sonication). These forces affect the true size of the aggregates formed in a unit operation, thereby losing representativity in terms of aggregates particle size. This study presents an alternative method of measuring the size distribution of particles with aggregation behavior, particularly, by using non-invasive microscopy and image processing and analysis. The samples used have been obtained from an experimental precipitation process by applying sulfidization to treat the cyanide-copper complexes contained in a cyanidation solution. This method has been validated with statistical tools and compared with a conventional analysis based on laser diffraction. Our results show significant differences between the methods analyzed, demonstrating that image processing and analysis by microscopy is an excellent and non-invasive alternative to obtaining size distribution of aggregates in precipitation processes.

Stainless steel 316L (SS316L) and titanium-alloy Ti6AL4V exhibit properties for bio-medical applications; however their tribocorrosion associated with metallosis is still a major concern. Therefore smoothing DLC coatings aiming for the improvement of tri-bocorrosion and cell viability of stainless steel 316L (SS316L) and titanium-alloy Ti6AL4V with and without DLC coatings were compared. The motivation was due to many papers detailing metallosis caused by metal debris in the body's soft tissues. Nowadays, metallosis is responsible for almost of prosthesis replacement surgeries. DLC coatings were produced using the Plasma Enhanced Chemical Vapor Deposition (PECVD) technique; acetylene gas was used as a carbon precursor, and silane gas produced an amorphous silicon interface between the DLC coating and metal substrate. A combined setup of techniques thoroughly evaluated the coatings considering chemical composition, coatings adhesion at a metallic substrate, scratch resistance, and tribocorrosion susceptibility. The cytotoxicity and genotoxicity of metallic samples with and without DLC coatings were analyzed, considering cell viability and its correlation with coatings’ chemical composition

Alterations in gene expressions are often due to epigenetic modifications that can lead to significant influence on cancer development, growth, and progression. The main epigenetic modifications observed in human are methylation and acetylation. In this regard, the HDAC inhibitors (HDACi) such as SAHA (Vorinostat), which can exert epigenetic alterations through impacting the acetylation status of histones, are in clinical trials as a new class of drugs with promising effects on the cancer growth and metastatic process. The small molecule RG7388 is a newly developed inhibitor that is specific for an oncogene-derived protein called MDM2, which is in clinical trials for the treatment of various types of cancers. One of the common characteristics for these two drugs is their ability to induce p21 expression through distinct mechanisms in MCF-7 and LNCaP cells. This difference was expected trigger cell cycle arrest and cell death through intra-cellular mechanisms that are not identical. Hence, the molecular mechanism whereby SAHA can induce cell cycle arrest and trigger necrosis, apoptosis or necroptosis is still evolving. Similarly, the ability of RG7388 for producing anticancer effect is undergoing thorough investigation, since it can produce p53 dependent and p53 independent effects. In this study we performed experiments to measure the cell cycle arrest effects of SAHA and RG7388 on using MCF-7 and LNCaP cells. The cytotoxicity, cell cycle arrest and apoptosis/necroptosis effects of the treatments were assessed by using Trypan Blue Dye Exclusion (TBDE) method, MTT assay, Fluorescence assay with DEVD-amc fluorogenic substrate and Immunoblotting methods. Our results from MCF-7 and LNCaP cells confirmed that SAHA and RG7388 treatments were able to induce cell death via combination of cell cycle arrest and cytotoxic mechanisms. We are speculating that our findings could lead to the development of newer treatments for breast and prostate cancers using this type of combinations.

Soil is a crucial component for plant growth, as it provides water, nutrients, and mechanical support. Various factors, such as crop cultivation, microflora, nutrient addition, and water availability, significantly affect soil properties. Maintaining soil health is important, and one approach is the introduction of native organisms with multifaceted activities. In this study, the effects of four native microbes (Trichoderma asperellum strain TAIK 1, Bacillus cabrialesii strain BIK3, Pseudomonas putida strain PIK1, and Pseudomonas otitidis strain POPS1) and their consortia on soil health, plant growth, and the incidence of stem rot disease caused by Sclerotium oryzae in rice are evaluated. Upon bioagent treatment of soil through seed treatment or soil application, variations in chemical properties of the soil were observed, viz., pH, Electrical Conductivity (EC), Organic Carbon (OC), available Soil Nitrogen (SN), Soil Phosphorus (SP), Soil Potassium (SK), and soil enzymes (urease, acid and alkaline phosphatase, dehydrogenase), compared to untreated soils. The treated seeds with the consortia of four native bioagents resulted in a significant increase in plant height (39.16%), number of panicles (30.29%), and average grain yield (41.36%) over control plants. Under controlled conditions, the bioagents-treated plants showed a 69.37% reduction in stem rot disease. The findings of this study indicate a positive correlation between soil properties and plant growth as well as a highly negative association with stem rot disease severity. The results suggest that using native bioagents as a management strategy can control stem rot disease and enhance crop productivity while reducing reliance on chemical interventions. These findings provide valuable insights for the development of sustainable agricultural practices that promote soil health, plant growth, and disease management.

Abstract: RNase Y is an endoribonuclease that governs global mRNA turnover/processing in Ba-cillus subtilis and likely many other bacteria. The enzyme is anchored at the cell membrane, a pseudo-compartmentalization that appears coherent with its task to initiate decay of mRNAs translated predominantly at the cell periphery. However, the reason and consequence for RNase Y attachment to the membrane are largely unknown. We have studied a strain expressing wild-type levels of a cytoplasmic form of RNase Y from the chromosomal locus. This strain exhibits a slow growth phenotype similar to an RNase Y null mutant. Genome-wide data show a significant effect on the expression of hundreds of genes. Certain RNA substrates clearly require RNase Y membrane attachment but others do not. We found no correlation between mRNA stabilization and the cellular location or function of encoded proteins. The Y-complex, an RNase Y specificity factor, appears to also recognize the cytoplasmic form of the enzyme which is able to restore wild-type levels of the corresponding transcripts. We propose that membrane attachment of RNase Y is required for the functional interaction with many coding and non-coding RNAs, for limiting the cleavage of certain substrates and potentially to avoid unfavorable competition between RNase Y and other ribonucleases like RNase J that have a similar evolutionarily conserved cleavage speci-ficity.

Background: Worldwide, around 73 million induced abortions take place every year. Of these, 45% are unsafe and can lead to complications. The evolution of the legal and practical landscape of abortion in the Democratic Republic of the Congo (DRC) over the last few years necessitates a re-examination of the experience of induced abortion, leading this study to measure the incidence of abortion among young women (15 to 29 years of age), as well as the heterogeneity of this problem according to the residence of these young women (slum vs. non-slum areas). Methodology: We used representative survey data on women aged 15–49 in Kinshasa, collected from December 2021 to April 2022. The survey included questions about the respondents’ and their closest confidants’ experience of induced abortion, including the methods and sources used. We estimated abortion incidence and heterogeneity over one year based on residence in the city of Kinshasa according to sociodemographic characteristics. Results: The incidence rate of induced abortion among the confidants (close friends) in 2021 was 131.5 per 1000 (95% CI: IQR 99.4–163.6). These rates were significantly higher than the corresponding estimates of those surveyed. The incidence of induced abortion was 24.4 per 1000 (95% CI: 15.8–32.9) abortions per 1000 women among the respondents. The incidence rates of induced abortion were much higher among the respondents residing in slums than among those residing in non-slums (29.2 vs. 13.0 per 1000; p &lt; 0.001). Conclusions: More precise estimates of the incidence of abortion indicate that the incidence rate of abortion was higher among young women residing in slums, who were unmarried and had no children. These incidences were higher among confidants than among respondents. There is still a lot of work to be done to fulfill the obligations outlined in the Maputo Protocol. This includes establishing easily accessible services that offer complete abortion care with a focus on women's needs, particularly in slum areas. The aim is to decrease the occurrence of unsafe abortions and their associated effects.

Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG) with periodic outbreaks of cold sores caused by virus reactivation in the TG and subsequent replication in the oral mucosa. While antiviral therapies can provide relief from cold sores, they are unable to eliminate HSV-1. We provide experimental results that highlight non-thermal plasma (NTP) as a new alternative therapy for HSV-1 infection that would resolve cold sores faster and reduce the establishment of latent infection in the TG. Additionally, this study is the first to explore the use of NTP as a therapy that can both treat and prevent human viral infections. We investigated the antiviral effect of NTP using an in vitro model for HSV-1 cold sores, involving the application of NTP from two separate devices to cell-free HSV-1, HSV-1-infected cells, and uninfected cells. We found NTP reduced the infectivity of cell-free HSV-1, reduced viral replication in HSV-1-infected cells, and diminished the susceptibility of uninfected cells to HSV-1 infection. This triad of antiviral mechanisms of action suggest the potential of NTP as a therapeutic agent effective against HSV-1 infection.

Standard Non-Melanoma Skin Cancer (NMSC) treatment involves surgery, recently combined with chemotherapy or immunotherapy in case of advanced tumors. Exosomes, integral to carcinogenesis, are found in NMSC, releasing mediators impacting tumor progression. Nevertheless, the precise intercellular signaling role of NMSC-derived exosomes remains unclear. This review aims to elucidate their potential role in NMSC diagnosis and treatment. A systematic review encompassed literature searches in electronic databases from inception to September 2023, based on certain inclusion and exclusion criteria, addressing NMSC-derived exosomes, their molecular cargo and their implications in the diagnosis, prognosis, and treatment of NMSC. Key components were identified. Extracellular vesicle (EV) proteins and RNA emerged as diagnostic biomarkers in EV-based liquid biopsy. Circular RNA CYP24A1, known for its molecular stability, holds promise as a diagnostic biomarker. Long noncoding RNAs (lincRNA-PICSAR) and Desmoglein 2 (DSg2) are linked to drug resistance, serving as prognostic biomarkers. EV mediators are actively investigated for their potential role as drug delivery agents. In conclusion, this systematic review showed that NMSC-derived EVs display promise as therapeutic targets and diagnostic biomarkers. Further research is imperative to fully comprehend exosome mechanisms and explore their potential in cancer diagnosis and treatment.

Diabetic retinopathy (DR) is a progressive blinding disease that affects vision and quality of life of patients and severely impacts society. This complication, caused by abnormal glucose metabolism, leads to structural, functional, molecular, and biochemical abnormalities in the retina. Oxidative stress (OS) and inflammation also play pivotal roles in the pathogenic process of DR, leading to mitochondrial damage and decrease in the mitochondrial function. DR causes retinal degeneration in glial and neural cells, while the disappearance of pericytes in retinal blood vessels leads to modifications in vascular regulation and stability. Clinical changes include dilatation and blood flow alterations in response to the reduce in retinal perfusion in retinal blood vessels, leading to vascular leakage, neovascularization and neurodegeneration. Thus, DR is a highly complex disease with various biological factors that contribute to its pathogenesis. The interplay between biochemical pathways and non-coding RNAs (ncRNAs) is essential for understanding the development and progression of DR. Abnormal expression of ncRNAs has been confirmed to promote the development of DR, suggesting that ncRNAs such as miRNAs, lnc-RNAs and circ-RNAs have potential as diagnostic biomarkers and theranostic targets in DR. This review provides an overview of interactions between abnormal biochemical pathways and dysregulated expression of ncRNAs under the influence of hyperglycemic environment in DR.

Carbohydrates such as fructooligosaccharides (FOS) are associated with improved gastrointestinal health and prevention of excess body fat. We evaluated the long-term effects of high amounts of FOS on metabolic parameters, non-alcoholic fatty liver disease (NAFLD) and short-chain fatty acids (SCFA). Sixty C57BL/6 mice received diets for four months: control (C), normolipid rich in fiber (F), normolipid supplemented with FOS (FOS), high fat (HL), high fat with high fiber (HLF) and high fat with FOS (HLFOS). We analyzed: animal weight; body composition; food intake; fasting blood glucose; serum and liver lipid profile; liver and intestinal histologies; malondialdehyde (MDA), hepatic retinol and α-tocopherol; SCFA in the feces. Supplementation with FOS in a high-fat diet promoted less body weight gain and reduced liver and retroperitoneal adipose tissue weights compared to HL and HF. FOS prevented NASH and decreased alanine aminotransferase and serum cholesterol levels in experimental animal models of obesity and metabolic syndrome (MS). There was found statistical differences in the dosages of the three main SCFAs in feces (acetic, isobutyric and isovaleric acids). Long-term supplementation with high doses of FOS was effective in reducing weight, adiposity, NAFLD and serum cholesterol in C57BL mice with obesity and MS induced by a high-fat diet.

The software design of autonomous vehicles (AVs) incorporates artificial intelligence (AI) characteristics to enhance their safety and overall driving performance. Central to vehicle’s operation is the ability to reason effectively in complex and uncertain environments. However, traditional logical systems, such as monotonic logic, often struggle to handle the inherent uncertainties and exceptions encountered in real-world scenarios. This paper proposes the utilization of non-monotonic logic in order to enhance the reasoning capabilities of autonomous vehicles. By incorporating non-monotonic reasoning, vehicles can navigate intricate traffic scenarios, make plausible inferences, and adapt their decisions when faced with conflicting information. This research aims to provide a comprehensive review of non-monotonic logic's application in autonomous vehicles, highlighting its advantages over traditional logical systems and its potential impact on safety and performance. Additionally, through this research, we seek to contribute to the advancement of autonomous driving technology by enhancing the reasoning capabilities of vehicles in various scenarios, such as car- following related to critical safety events. The personalized cognitive agent is proposed in driving behavior to consider particularly in their assumptions of homogeneous drivers. The personalized cognitive agent is incorporating heterogeneous driving behaviors, based on individual user preferences, characteristics, and needs. Driving behavior is a complex interplay of various factors, encompassing both human and external elements. Human factors, including age, experience, and gender, contribute significantly to how individuals navigate the roads. These factors influence decisions, reactions, and risk-taking tendencies on the part of drivers. Additionally, external factors such as weather conditions further compound this intricate dynamic, requiring drivers to adapt their behavior to the prevailing environment. The goal of a personalized cognitive agent is to provide tailored and customized experiences to cognitive vehicles, taking into account the unique requirements and individual preferences of occupants inside autonomous vehicles.

The non-coding RNAs (ncRNAs) are indispensable for controlling genes and genetic programming during development, as well as for health and cardiovascular diseases. Cardiac arrhythmia is a frequent cardiovascular disease, which has a complex pathology. Recent studies have shown that ncRNAs are also associated with cardiac arrhythmias. Many non-coding RNAs and/or genomes have been reported as a genetic background for cardiac arrhythmias. Arrhythmias may be affected by several functional and structural changes in the myocardium. Therefore, ncRNAs might be indispensable regulators of gene expression in cardiomyocytes, which could play a dynamic role in regulating the stability of cardiac conduction and/or in the remodeling process. Although it remains almost unclear how ncRNAs regulate the expression of molecules for controlling the cardiac conduction and/or in the remodeling process, gut microbiota and immune system within the intricate networks might be involved in the regulatory mechanisms. This study would discuss them and provide a research basis for ncRNAs modulation, which might support the development of emerging innovative therapies against cardiac arrhythmias.

Inflammasomes are multiprotein complexes that activate inflammatory responses by inducing pyroptosis and secretion of pro-inflammatory cytokines. Along with many previous studies on inflammatory responses and diseases induced by canonical inflammasomes, an increasing number of studies have demonstrated that non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4 inflammasomes, are emerging key players in inflammatory responses and various diseases. Flavonoids are natural bioactive compounds found in plants, fruits, vegetables, and teas and have pharmacological properties in a wide range of human diseases. Many studies have successfully demonstrated that flavonoids play an anti-inflammatory role and ameliorate many inflammatory diseases by inhibiting canonical inflammasomes. Others have demonstrated the anti-inflammatory roles of flavonoids in inflammatory responses and various diseases, with a new mechanism by which flavonoids inhibit non-canonical inflammasomes. This review discusses recent studies that have investigated the anti-inflammatory roles and pharmacological properties of flavonoids in inflammatory responses and diseases induced by non-canonical inflammasomes and further provides insight into developing flavonoid-based therapeutics as potential nutraceuticals against human inflammatory diseases.

Vitamin E facilitates testicular development and semen quality in farm animal. And most research tends to investigate antioxidant roles of Vitamin E in reproductive health; some research also find potential non-antioxidant roles of Vitamin E. To further uncover the mechanism by which Vitamin E modulates reproductive health, the paper reviews specific function of Vitamin E and candidate genes involved in male reproductive performance promoted by Vitamin E. The review found that cell proliferation (PDPN, BMP, Myc, AMPKa, GSK3β, PPARγ, CDK4, CDK6, Ki67, PCNA, Cyclin A2, Cyclin B1, Cyclin B3, BLM, REL, KLHL25)-, cell apoptosis (BCL-2, Caspase 9, Bax)-, spermatogenesis (CatSper1, CatSper2, NDRG1, CYP26B1, FSCN3, FLNA, SPCS3, YBX3, RARS)-, hormone receptor (PGR, FSHR, AR)-related genes are the underlying key points. And two miRNAs, miR-107 and miR-493-3p, which mediate cell cycle process, are also identified in response to Vitamin E treatment. The paper paves the way for a comprehensive understanding about effect of Vitamin E on testis development and semen quality in domestic animals.

This article develops a duality principle and a related convex dual formulation suitable for a large class of models in physics and engineering. The results are based on standard tools of functional analysis, calculus of variations and duality theory. In particular, we develop applications to a model in non-linear elasticity.

On a rotating disk, two particles bounce at the vertices of a regular polygon in opposite directions. On the return to the entry point, a clock measures the time difference, called Sagnac effect. Due to Coriolis effects, the counterclockwise and clockwise paths are different. The particular case of the slow disk where the two trajectories are very close and almost polygonal is studied. The existence of a transition between a classical and a relativistic regime is proved. An experimental verification is proposed. Although the two Sagnac effects seem analogous, in detail their behavior is quite different.

Complex problem-solving (CPS) tasks have become an increasingly popular tool for understand-ing and assessing cognitive ability. These tasks have been repeatedly shown to be predictors of academic and workplace success above and beyond traditional measures of general intelligence and fluid intelligence. To date, there has been little exploration of the underlying mechanisms that drive this additional predictive utility. In this study, we examined the role of a variety of non-cognitive personality and investment traits that could drive performance on CPS tasks. Adult participants (n = 152) were recruited via M-Turk and completed a battery of personality and in-vestment trait measures, a measure of general mental ability, and a 61-trial microworlds-style CPS task. Generalised linear mixed-effects models revealed a wide variety of personality and in-vestment traits influenced task performance above and beyond general mental ability. Specifical-ly, two clusters of traits emerged as important determinants of performance: one cluster that in-fluenced the capacity to deal with the introduction of system randomness (Conscientiousness and Extraversion) and one cluster that influenced the capacity to deal with the introduction of system delays (NFC, Learning Goal Orientation, and Intellect). These findings suggest that CPS tasks do capture more than just general mental ability and may be good predictors of academic and workplace success because they tap into both cognitive ability and the motivation and willingness to engage in cognitive exploration and mental effort.

The COVID-19 pandemic has caused significant medical and psychological challenges worldwide, and not only exceeded the capacity of hospitals and intensive care units but also an individuals’ ability to cope with life. Health-care workers have continued to provide care for patients despite exhaustion, fear of transmission to themselves and their family, illness or death of friends and colleagues, and losing many patients. They have also faced additional stress and anxiety due to long shifts combined with unprecedented population restrictions, including personal isolation. In this study, we study the effect of an app-based Yoga of Immortals (YOI) intervention on mental health of healthcare workers. In this study, the health care workers were digitally recruited, and their psychological parameters were measured using validated questionaries. The participants were randomly grouped into control and test groups. The validated psychological measures were the Patient Health Questionnaire-8 (PHQ-8), Insomnia Severity Index (ISI) and generalized anxiety disorder (GAD-7) scales. The digital YOI intervention significantly reduced the anxiety, depression symptoms, and insomnia in healthcare workers of all age groups. In contrast, there was no improvement in the control group. This study details the effectiveness of an app-based YOI intervention in healthcare workers.

In experimental physics, we understand time as the duration of material changes that run into space. This fact is the standpoint for our model of time-invariant space in which causality is only a principle and not a physical actuality, and entropy runs only in space and not in time. Time is merely a duration of entropy that is increasing in time-invariant space. Time is entering existence when measured by the observer. In time-invariant space, motion happens only in space and not in time which means that also in open timelike curves motion happens only in space and not in time.

Simultaneous extraction of trypsin inhibitors and soy isoflavones from soybean meal was investigated using the non-destructive phytochemical extraction process, namely aqueous micellar system. The ethoxylated aliphatic alcohols Genapol X-080, Tergitol 15-S-7, and Tergitol 15-S-9, all non-toxic and biodegradable surfactants, were assessed as potential extractants. A Box-Behnken multifactorial design with the application of the Derringer desirability was used to determine the conditions that maximized the trypsin inhibitors and isoflavone extraction while minimizing the protein extraction. The optimum condition of 5% m/m of surfactant in 50 mM aqueous sodium citrate solution pH 4.5, at 45 °C for 45 min, was established for the three surfactants. The novel methodology would allow the extraction of the main soybean antinutritional factors, trypsin inhibitors, and the valuable isoflavones, preserving the nutritional quality of the treated material. This represents a sustainable alternative methodology for industrial purposes due to its low cost, biodegradability, non-toxicity, and easy scaling up.

Electrical transmission between neurons is largely mediated by gap junctions. These junctions allow the direct flow of electric current between neurons, and in mammals are mostly composed of the protein connexin (Cx)36. Circuits of electrically coupled neurons are widespread in these animals, plus, experimental and theoretical evidence supports the notion that, beyond synchronicity, these circuits are able to perform sophisticated operations like lateral excitation and inhibition, noise reduction, as well as the ability to selectively respond upon coincident excitatory inputs. Although once considered stereotyped and unmodifiable, we now know that electrical synapses are subject to modulation and, by reconfiguring neural circuits, these modulations can alter relevant operations. The strength of electrical synapses depends on gap junction conductance, as well as on its functional interaction with the electrophysiological properties of coupled neurons. In particular, voltage dependent channels of the non-synaptic membrane critically determine the efficacy of transmission at these contacts. Consistently, modulatory actions on these channels have been shown to represent relevant mechanisms of plasticity of electrical synaptic transmission. Here we review recent evidence on the regulation of electrical synapses of mammals, the underlying molecular mechanisms, and the possible ways in which they affect circuit function.

Aquaponics are efficient systems that associate aquatic organisms’ production and plants by recirculating water and nutrients between aquaculture and hydroponic tanks. In this study, we have characterised the bacterial communities in the fresh water aquaponics system that can mineralise polysaccharides and phytate by producing carbohydrate degrading enzymes and phytases, by 16S rRNA gene sequencing and in vitro culture techniques. Around 20% of the operational taxonomic units (OTUs) identified were previously reported to carry fibre-degrading enzymes putative genes, namely β-glucanase (1%), xylanase (5%) or cellulases (17%). Ten % of the OTUs were previously reported to carry putative genes of phytases with different catalytic mechanisms, namely β-propeller (6%), histidine acid phytases (3%) and protein tyrosine phytase (&lt;1%). Thirty-eight morphologically different bacteria were isolated from biofilms accumulated in fish and plant compartments, and identified to belong to the Bacilli class. Among these, seven could produce xylanase, 8 produced β-glucanase, 14 produced cellulase, and 11 isolates could secrete amylases. In addition, Staphylococcus sp. and Rossellomorea sp. could produce consistent extracellular phytate-degrading activity. The PCR amplification of β-propeller genes both in environmental samples and in the isolates obtained showed that this is the most ecologically relevant phytase type in the aquaponics systems used. In summary, the aquaponics system is abundant with bacteria carrying enzymes responsible for plant-nutrient mineralisation.

Background Reliable and field-applicable diagnosis of schistosome infections in non-human animals is important for surveillance, control, and verification of interruption of human schistosomiasis transmission. This study aimed to summarize uses of available diagnostic techniques through a systematic review and meta-analysis. Methods and principal findings We systematically searched the literature and reports comparing two or more diagnostic tests in non-human animals for schistosome infection. Out of 4,909 articles and reports screened, 18 met our inclusion criteria, four of which were considered in the meta-analysis. A total of 14 techniques (parasitologic, immunologic, and molecular) and nine types of non-human animals were involved in the studies. Notably, four studies compared parasitologic tests (miracidium hatching test (MHT), Kato-Katz (KK), the Danish Bilharziasis Laboratory technique (DBL), and formalin-ethyl acetate sedimentation-digestion (FED-SD)) with quantitative polymerase chain reaction (qPCR), and sensitivity estimates (using qPCR as the reference) were extracted and included in the meta-analyses, showing significant heterogeneity across studies and animals hosts. The pooled estimate of sensitivity was 0.21 (95% confidence interval (CI): 0.03 – 0.48) with FED-SD showing highest sensitivity (0.89, 95% CI: 0.65 – 1.00). Conclusions and significance Our findings suggest that the parasitologic technique FEA-SD and the molecular technique, qPCR, are the most promising field-applicable techniques for schistosome diagnosis in non-human animal hosts. Future studies are needed for validation and standardization of the techniques for real-world field applications.

Mucorales are the causal agents for the lethal disease known as mucormycosis. Mortality rates of mucormycosis can reach up to 90%, due to the mucoralean antifungal drug resistance and the lack of effective therapies. A concerning urgency among the medical and scientific community claims to find targets for the development of new treatments. Here, we reviewed different studies de-scribing the role and machinery of a novel non-canonical RNAi pathway (NCRIP) only conserved in Mucorales. Its non-canonical features are the independence of Dicer and Argonautes proteins. Conversely, NCRIP relies on RNA-dependent RNA Polymerases and an atypical ribonuclease III (RNaseIII). NCRIP regulates the expression of mRNAs by degrading them in a specific manner. Its mechanism binds dsRNA but only cuts ssRNA. NCRIP exhibits a diversity of functional roles. It represses the epimutational pathway and the lack of NCRIP increases the generation of drug resistant strains. NCRIP also regulates the control of retrotransposons expression, playing an essential role in genome stability. Finally, NCRIP regulates the response during phagocytosis, affecting the multifactorial process of virulence. These critical NCRIP roles in virulence and antifungal drug resistance, along with its exclusive presence in Mucorales, mark this pathway as a promising target to fight against mucormycosis.

The steady-state multiplicity of the porous, non-isothermal, catalyst pellet when two parallel and consecutive chemical reactions take place was analysed in this work. The geometry selected for the catalyst pellet is finite hollow cylinder. A numerical multigrid continuation technique with the preconditioned conjugate gradient squared as coarse grid solver was used. The continuation parameter is the dimensionless adiabatic heat rise (Prater number) for the first chemical reaction. The effect of the other governing parameters was analysed and the results are compared to those provided by the single chemical reaction.

It was recently demonstrated that a co-planar capacitive sensor could be applied to the evaluation of materials without the disadvantages associated with the other techniques. This technique effectively detects changes in the dielectric properties of the materials due to, for instance, imperfections or variations in the internal structure, by moving a set of simple electrodes on the surface of the specimen. An AC voltage is applied to one or more electrodes and signals are detected by others. This is a promising inspection method for imaging the interior structure of the numerous materials, without the necessity to be in contact with the surface of the sample. In this paper, Finite Element (FE) modelling was employed to simulate the electric field distribution from a co-planar capacitive sensor and the way it interacts with a non-conducting sample. Physical experiments with a prototype capacitive sensor were also performed on a Plexiglas sample with sub-surface defects, to assess the imaging performance of the sensor. A good qualitative agreement was observed between the numerical simulation and experimental result.

Glioma accounts for 80% of all malignant brain tumors and is the most common adult primary brain tumor. Age is an important factor affecting the development of cancer as somatic mutations accumulate with age. In this study, we aimed to analyze the significance of age-related non-silent somatic mutations in glioma prognosis. Histological tumor grade depends on age at diagnosis in patients with IDH1, TP53, ATRX, and EGFR mutations. The hierarchical clustering of patients was dominantly separated by IDH1 and EGFR mutations. Furthermore, patients with IDH1 mutation were dominantly separated by TP53 and ATRX double mutation and its double wildtype counterpart. Patients with the double mutation showed poorer prognosis than those with the double wild type genotype. In conclusion, among the many somatic mutations, those in IDH1, TP53, ATRX, and EGFR are important for glioma classification based on histological grade. Patients with EGFR mutation had the poorest prognosis, whereas those with only IDH1 mutation showed the best prognosis.

On-farm research was conducted at Gouripur sub-district under Mymensingh district of Bangladesh during the boro (mid November-June) season in 2013-14 and 2014-15 to evaluate the performance of non-puddled rice cultivation with and without crop residue retention. The rice var. BRRI dhan28 was transplanted by two tillage practices viz., puddled conventional tillage (CT) and non-puddled strip tillage (ST) and at two levels of mustard residues, i.e., no residue (R₀) and 50% residue (R₅₀). The experiment was designed in a randomized complete block design with four replications. There were no significant yield differences between tillage practices and residue levels in 2013-14. But in the following year, ST yielded 9% more grain compared to CT leading to 22% higher BCR. Retention of 50% residue increased yield by 3% compared to no-residue, which contributed to 10% higher benefit-cost ratio (BCR). The ST combined with 50% residue retention yielded the highest grain yield (5.81 t ha^-1) which contributed to produce the highest BCR (1.06).

A 12 year old boy was diagnosed with temporal lobe epilepsy (TLE) along with mesial temporal sclerosis based on MRI (magnetic resonance imaging) results. The diagnosis was further confirmed by genetic analysis. He also had minor psychiatric symptoms of obsessive-compulsive disorders and mood swings. After 4 years of treatment with Sodium Valproate no change in symptoms was observed. Genetic testing along with deep phenotyping revealed altered glutamate pathway and metabolism. Post genetic testing the patient was put on a combination of Sodium Valproate and Valproic acid along with supplementation of N-acetylcysteine (NAC), Cyanocobalamin, Pyridoxine and Cholecalciferol. Within three months of this combined therapy the patient experienced complete elimination of seizures and drastic improvement in mood and social behaviour. The case report highlights the importance of precision diagnosis in understanding the underlying perturbed pathways in structural epilepsy like TLE and demonstrates the importance of non-invasive targeted therapy in such cases.

For the electromagnetic eddy current testing, various methods have been proposed for reducing the lift-off error on the measurement of samples. In this paper, instead of eliminating the measurement error caused by the lift-off effect, an algorithm has been proposed to directly measure the lift-off distance between the sensor and non-magnetic conductive plates. The algorithm is based on a sample-independent inductance (SII) feature. That is, under high working frequencies, the inductance is found sensitive to the lift-off distance and independent of the test piece under an optimal single high working frequency (43.87 kHz). Furthermore, the predicted lift-off distance is used for the thickness prediction of the non-magnetic conductive samples using an iterative method. Considering the eddy current skin depth, the thickness prediction is operated under a single lower frequency (0.20 kHz). As the inductance has different sensitivities to the lift-off and thickness, the prediction error of the sample thickness is different from that of the lift-off distance. From the experiments on three different nonmagnetic samples – aluminium, copper, and brass, the maximum prediction error of the lift-off distance and sample thickness is 1.1 mm and 5.42 % respectively at the lift-off of 12.0 mm.

During chronic liver injury, inflammation leads to liver fibrosis— particularly due to the activation of hepatic stellate cells (HSCs). However, the involvement of inflammatory cytokines in HSC activation and the relationship among different liver cells is unclear. To examine their interactions, many in vitro liver models are performed in organoid or spheroid culture with random 3D structure, complicating analysis. Herein, we demonstrated the hierarchical coculture of primary rat hepatocytes with non-parenchymal cells such as the human-derived HSC line (LX-2) and liver sinusoidal endothelial cell line (TMNK-1). The cocultured tissue had high usability with simple operation of separating solid and liquid phases with improved liver functions such as albumin production and hepatic cytochrome P450 3A4 activity. We also studied the effects of stimulation by both oxygen tension and the key pro-fibrogenic cytokine, transforming growth factor beta (TGF-β), on HSC activation. Gene expression analysis revealed that lower oxygen tension and TGF-β1 stimulation enhanced collagen type I and alpha-smooth muscle actin expression from LX-2 cells in the hierarchical coculture. Therefore, this hierarchical in vitro cocultured liver tissue could provide an improved platform as a disease model for elucidating the interactions of various liver cell types and biochemical signals in future liver fibrogenesis studies.

Non-homologous end-joining (NHEJ) is a DNA repair pathway required to detect, process, and ligate DNA double-stranded breaks (DSBs) throughout the cell cycle. The NHEJ pathway is necessary for V(D)J recombination in developing B and T lymphocytes. During NHEJ, Ku70 and Ku80 form a heterodimer that recognizes DSBs and promotes recruitment and function of downstream factors PAXX, MRI, DNA-PKcs, Artemis, XLF, XRCC4, and LIG4. Mutations in several known NHEJ genes result in severe combined immunodeficiency (SCID). Inactivation of Mri, Paxx or Xlf in mice results in normal or mild phenotype, while combined inactivation of Xlf/Mri, Xlf/Paxx, or Xlf/Dna-pkcs leads to late embryonic lethality. Here, we describe three new mouse models. We demonstrate that deletion of Trp53 rescues embryonic lethality in mice with combined deficiencies of Xlf and Mri. Furthermore, Xlf^-/-Mri^-/-Trp53^+/- and Xlf^-/-Paxx^-/-Trp53^+/- mice possess reduced body weight, severely reduced mature lymphocyte counts, and accumulation of progenitor B cells. We also report that combined inactivation of Mri/Paxx results in live-born mice with modest phenotype, and combined inactivation of Mri/Dna-pkcs results in embryonic lethality. Therefore, we conclude that XLF is functionally redundant with MRI and PAXX during lymphocyte development in vivo. Moreover, Mri genetically interacts with Dna-pkcs and Paxx.

Corporate governance is widely suggested by economists and regulators as a solution to reduce agency problems and improve firm performance. However previous studies have failed to generate consistent results. Using a dynamic panel system GMM estimator to alleviate endogeneity concerns we determine the effect of corporate board structure on the performance of a panel of 1265 Chinese firms listed on the Shanghai and Shenzhen stock exchanges from 2010 to 2016. We compare the dynamic system GMM estimator to some commonly used estimators; ordinary least squares (OLS), fixed effects (FE) and the dynamic OLS, and show that these estimates are biased due to endogeneity. The dynamic system GMM estimator incorporates the dynamic nature of internal governance choices to provide valid and powerful instruments that address unobserved heterogeneity and simultaneity. Our results show support for the board model corporate governance mechanism. We find that board size is positive and significantly related to both return on assets and total net profit margin. In addition board independence is positive and significantly related to return on assets but insignificantly related to total net profit margin. Duality was found to have a negative but statistically insignificant relation with firm performance.

An experiment was carried out at Nabogram Khamarbari, near the Manannogor, Sadar Upazila, Noakhali District, Noakhali-3814, Bangladesh during the period from 12th January 2018 to 17th April 2018, with two varieties of tomatillo (Physalis ixocarpa Brot.) SAU tomatillo-1 and SAU tomatillo-2. It was laid out in RCBD method having three replications and was conducted to observe the influence of staking and non-staking on tomatillo cultivation in coastal areas. For the study, growth indicating characters like no. of leaves plant^-1, size of leaf plant^-1, height of each plant, no. of branches plant^-1 and yield attributing parameters such as days to first flowering, days to 50% flowering, no. of fruits branch^-1, fruit weight and yield were obtained from the plants with the treatments of staking and non-staking. A wide variation was observed between two varieties of tomatillo with the effect of these treatments. According to the results highest no. of leaves branch^-1, maximum size of leaves branch^-1, tallest height of each plant, uppermost no. of branches plant^-1, highest no. of fruits branch^-1, maximum weight of each fruit and yield were obtained in the staking treatment over the non-staking treatment of SAU tomatillo-1 and in case of SAU tomatillo-2, with the same parameters the result indicated significantly upper in the staking treatment over non-staking treatment. Considering the two varieties of tomatillo, the outcome were significantly superior with staking treatment for the similar parameters. The findings of the experiment indicated that the best yield (21 tha¹) and highest financial benefit could be obtained by SAU tomatillo-1 and the best tomatillo production in saline soil of coastal areas is possible by cultivating SAU tomatillo-1.

This study examines the effect of market risk on the financial performance of 31 non-financial companies listed on the Casablanca Stock Exchange (CSE) over the period 2000-2016. We utilize three alternative variables to assess financial performance, namely return on assets, return on equity and profit margin. Next, we use the degree of financial leverage, the book-to-market ratio, and the gearing ratio as market risk variables. Besides, we employ the pooled OLS model, the fixed effects model, the random-effects model, the difference GMM and the system GMM models. The results show that market risk indicators have a negative and significant influence on the companies' financial performance. The elasticities are greater following the book-to-market ratio compared to the degree of financial leverage and the gearing ratio, respectively. In most cases, the firm size, the tangibility ratio, and the cash holdings ratio have a positive effect on financial performance, whereas the firms' age, the debt-to-income ratio, stock turnover, and leverage hurt the performance of these non-financial companies. Therefore, decision-makers and managers should mitigate market risk through appropriate strategies of risk management, such as derivatives and insurance techniques.

Reservoir computers (RCs) are a biology inspired computational framework for signal processing typically implemented using recurrent neural networks. Recent work has shown that Boolean networks (BN) can also be used as reservoirs. We analyze the performance of BN RCs, measuring their flexibility and identifying factors that determine effective approximation of Boolean functions that are applied in a sliding-window fashion over a binary signal, either non-recursively or recursively. We train and test BN RCs of different sizes, signal connectivity, and in-degree to approximate 3-bit, 5-bit and 3-bit recursive binary functions. We analyze how BN RC parameters and function average sensitivity, a measure of function smoothness, affect approximation accuracy as well as the spread of accuracies for a single reservoir. We found that approximation accuracy and reservoir flexibility are highly dependent on RC parameters. Overall, our results indicate that not all reservoirs are equally flexible and RC instantiation and training can be more efficient if this is taken into account. The optimum range of RC parameters opens up an angle of exploration for understanding how biological systems might be tuned to balance system restraints with processing capacity.

Free vibration analysis of the porous functionally graded circular plates has been presented on the basis of classical plate theory. The three defined coupled equations of motion of the porous functionally graded circular/annular plate were decoupled to one differential equation of free transverse vibrations of plate. The one universal general solution was obtained as linear combination of the multiparametric special functions for the functionally graded circular and annular plates with even and uneven porosity distributions. The multiparametric frequency equations of functionally graded porous circular plate with diverse boundary conditions were obtained in the exact closed-form. The influences of the even and uneven distributions of porosity, power-law index, diverse boundary conditions and the negligibled effect of the coupling in-plane and transverse displacements on the dimensionless frequencies of the circular plate were comprehensively studied for the first time. The formulated boundary value problem, the exact method of solution and the numerical results for the perfect and imperfect functionally graded circular plates have not yet been reported.

Depending on human body conditions and environmental conditions, it is sometimes difficult to conduct subject experiments. In such cases, it is effective to use a thermal manikin. There are few studies that investigate the effect of the non-uniform and asymmetric outdoor thermal environment on the mean skin temperature. The purpose of this study is to clarify the influence of the non-uniform and asymmetric thermal radiation of short-wavelength solar radiation in an outdoor environment on the calculation of the mean skin temperature. The skin temperature of the front of the coronal surface, which was facing the sun and where the body received direct short-wavelength solar radiation, and the skin temperature of the rear of the coronal surface, which was in the shadow and did not receive direct short-wavelength solar radiation were respectively measured. The feet, upper arm, forearm, hand and lower leg, which are susceptible to short-wavelength solar radiation in a standing posture, had a noticeable difference in skin temperature between sites in the sun and in shade. The mean skin temperature of sites facing the sun was significantly higher than the mean skin temperature of those in the shade.

The article presents the results of research on a new method of spatial analysis of walls and buildings moisture. Due to the fact that destructive methods are not suitable for historical buildings of great architectural significance, a non-destructive method based on electrical tomography has been adopted. A hybrid tomograph with special sensors was developed for the measurements. This device enables the acquisition of data, which are then reconstructed by appropriately developed methods enabling spatial analysis of wet buildings. Special electrodes that ensure good contact with the surface of porous building materials such as bricks and cement were introduced. During the research, a group of algorithms enabling supervised machine learning was analyzed. They have been used in the process of converting input electrical values into conductance depicted by the output image pixels. The conductance values of individual pixels of the output vector made it possible to obtain images of the interior of building walls, both flat intersections (2D) and spatial (3D) images. The presented group of algorithms has a high application value. The main advantages of the new methods are: high accuracy of imaging, low costs, high processing speed, ease of application to walls of various thickness and irregular surface. By comparing the results of tomographic reconstructions, the most efficient algorithms were identified.

Background: Alzheimer's Disease (AD) is a progressive and incurable condition that prompts the exploration of interventions to slow its advancement and enhance the quality of life. The cortical brain waves could have a role in the process of executive function deterioration, increasing dementia symptoms. Objective: To interrogate the effects of physical exercise, and non-invasive brain stimulation, both in electrophysiological behavior of the brain, the executive functions, and dementia symptoms in older adults with AD. Methods: One hundred and sixteen older adults were grouped (n=22 each): GAE (AD, PMED+NIBS), GCP (AD, PMED), GCN (AD, NIBS), GCS (control, no intervention). Binaural beats were used as a non-invasive brain stimulation, physical exercise, or both, were applied during 16 weeks. Pre/post measurements included Alpha Band, and SMR Rhythms, executive functions, and dementia symptoms. Results: GCS showed no significant changes (p>0.05). GCN and GCS slightly enhanced inhibitory control (p>0.05) and working memory (p>0.05). In contrast, GCP and GAE improved executive function (p

First-line treatment for advanced large-cell neuroendocrine carcinoma of the lung (LCNEC) has limited efficacy. This study aimed to explore the efficacy and safety of everolimus combined with EP regimen chemotherapy (etoposide + cisplatin, EP) in the first-line treatment for LCNEC. The patients were randomly assigned to the experimental or control group, with 20 patients in each group. The experimental group received the mTOR inhibitor everolimus 5 mg once a day combined with EP ivgtt, d1-3, every 3 weeks for 4–6 cycles. The control group received EP only and the infusion method was the same as that of the experimental group. The safety in the experimental group was controllable and not inferior to that in the control group. Serious adverse effects were observed in approximately 10% of patients. Objective response rate (ORR) for the experimental and control groups were 15% vs. 0 (P=0.231), disease control rate (DCR) was 100% vs. 32% (P

Dendritic cells (DCs) are the most specialized antigen-presenting cells and lymph nodes (LNs) play an important role in the DC-mediated T-cell response. We evaluated the infiltration of CD1a-positive DCs (CD1a-DCs) i.e. immature DCs, and S100-positive dendritic cells (S100-DCs), a mixture of immature- and mature DCs, in 73 cases of laryngeal cancer and its regional LNs. Among them, 31 patients underwent radiotherapy (RT) or chemoradiotherapy (CRT) prior to surgery. No significant difference was found for CD1a-DC infiltration in the primary tumor, metastatic LNs and non-metastatic LNs, while S100-DCs were significantly fewer in number in the primary tumor and metastatic LNs compared to non-metastatic LNs. Cases which showed a high infiltration of S100-DCs in metastatic LNs appeared to show a favorable prognosis although statistical significance was not reached. In the RT/CRT group, infiltration of CD1a-DCs and S100-DCs were fewer in the primary tumor and metastatic LNs compared to the treatment naive group. Conversely, the RT/CRT group showed higher CD1a-DCs and S100-DCs numbers in non-metastatic LNs compared to the treatment naïve group. Thus, DC maturation in metastatic LNs plays an important role in tumor immunity in laryngeal cancer, and infiltration of DCs into the primary tumor and metastatic LNs is impaired by RT/CRT.

Formaldehyde, sulfuric acid and salicylic acid were combined to create 3,3’-methylenebis[2-hydroxybenzoic acid] (MHB) ligand, which was subsequently permitted to bind with zinc ions. The ligand and its zinc (II) complex (Zn-MHB) have been described by a combination of elemental analyses, spectral (UV-Vis, IR, MS, NMR), XRD, TEM as well as TGA measurement. The ligand has been suggested to coordinate to the zinc center in tetradentate manner forming binuclear tetrahedral complex. An X-ray analysis indicated a considerable difference between MHB (crystalline) and Zn-MHB (amorphous). UV-Vis spectra were used to determine the optical properties such as bandgap, refractive index, optical conductivity and penetration depth. Possibility of employing the samples for optoelectronic applications was indicated from the band gap values which underlie the range of semiconductors. TEM revealed spherical shapes and mutation of ligand particles into nano-scale by complexation. The antimicrobial potential of the MHB towards gram-positive and negative bacterial growths has been investigated. The results suggested that it would be possible to employ MHB to stop bacterial development, particularly salmonella typhimurium. Cytotoxicity of the MHB was assessed against two types of mammalian cells: VERO (the kidney of an African green monkey) and HFB4 (human skin melanocytes). Lower sensitivity was observed in VERO cells.

The T cell composition of the tumor microenvironment (TME) of esophageal adenocarcinoma (EAC) in comparison to the T cell composition of the TME of Barrett esophagus (BE) and in the context of clinicopathologic features and patient survival is unknown. To help fill these knowledge gaps, we used a multiplex immunofluorescence platform to study adaptive T cells and T cell subtypes based on costimulatory/inhibitory markers in EAC (n=54) and matched BE (n=21) samples from 54 patients with EAC and correlated the T cell phenotype distribution with clinicopathologic features and disease-free survival. We observed significant enrichment of cytotoxic T cells (CTCs), memory T cells, effector memory T cells, memory T regulatory cells (MTregs), and T cells expressing costimulatory/inhibitory markers LAG3, TIM3, and ICOS in EAC compared to BE, in the stroma. In EAC, increased TIM3 expression on T cells significantly correlated with increased CTCs but not T regulatory cells (Tregs). In EAC, higher densities of Tregs and MTregs correlated with pT1 disease, low pathologic stage, and absence of lymphovascular invasion. In EAC, patients with higher density of TIM3-expressing T cells had shorter disease-free survival by univariate and multivariate analyses. Our results identify T cell subtypes that are relevant to EAC biology and patient outcome. Furthermore, our results identify TIM3 as a potential target for optimization of immunomodulatory therapy in EAC.

Abstract: Mast cell (MC) specific proteases are of particular interest for space biology and medicine due to their biological activity in regulating targets of a specific tissue microenvironment. MC tryptase and chymase obtain the ability to remodel connective tissue through direct and indirect mechanisms. Yet, MC specific protease expression under space flight conditions has not been adequately investigated. Using immunohistochemical stainings, we analyzed in this study the protease profile of the jejunal, gastric and hepatic MC populations in three groups of Mongolian gerbils - vivarium control, synchronous experiment, and 12-day orbital flight on the Foton-M3 spacecraft, - and in two groups - vivarium control and anti-orthostatic suspension - included in the experiment simulating effects of weightlessness in the ground-based conditions. After a space flight, there was a decreased number of MCs in the studied organs combined with an increased proportion of chymase-positive MCs and MCs with a simultaneous content of tryptase and chymase; the secretion of specific proteases into the extracellular matrix increased. These changes in the expression of proteases were observed both in the mucosal and connective tissue MC subpopulations of the stomach and jejunum. Notably, the relative content of tryptase-positive MCs in the studied organs of the digestive system decreased. Space flight conditions simulated in the synchronous experiment caused no similar significant changes in the protease profile of MC populations. The space flight conditions resulted in an increased chymase expression combined with a decreased total number of protease-positive MCs apparently due to participating in the processes of extracellular matrix remodeling and regulating the state of the cardiovascular system.

Neurotoxicity belongs to the leading factors inducing neurodegeneration-related diseases, such as Alzheimer’s (AD) and Parkinson’s disease. In particular, accumulation of β-amyloid proteins in the brain, a hallmark in AD, induces oxidative stress and neurotoxicity. The use of antioxidants in AD is not sufficiently effective and other pharmacological approaches tested failed to cure, prevent or retard the progression of the disease. Clinical studies indicated that several medicinal plants display beneficial effects by improving memory and cognitive functions of patients with mild and moderate AD. In this study, the potential antioxidant and neuroprotective properties of Olea europea, Crocus sativus and Salvia spp extracts, as well as their main active compounds on cell viability was evaluated using an in vitro model of AD, the differentiated human SH-SY5Y neuroblastoma cells to cholinergic neurons. Their effects were assessed against the H2O2- and β-amyloid- induced cell toxicity using the MTS test. Current findings indicated that Salvia fruticosa, S. officinalis, S. argentea leaf extracts and the active compounds, oleuropein, trans-crocin-3 and -4 display significant dose-dependent antioxidant and neuroprotective properties. It is of note though that the total phenolic fragment of Olea europea leaf extract includes several toxic compounds, such as oleocanthal, that markedly reduce cell viability and exacerbate the H2O2- and Aβ-induced cell toxicity. In addition, the Crocus sativus hydrophilic and diethyl ether extracts and all their active compounds tested markedly increased the H2O2-induced cell toxicity. In conclusion, the medicinal plants tested contain several compounds displaying dose-dependent effects against H2O2- and Aβ-induced neurotoxicity and could be used in AD, but they also contain several neurotoxic agents.

Hypercholesterolemia is a major risk for the development of cardiovascular diseases (CVDs), the main cause of mortality worldwide, and it is characterized by high levels of circulating cholesterol. The drugs currently available for hypercholesterolemia control have several side effects, so it is necessary to develop new effective and safer therapies. Seaweeds serve as sources of several bio-active compounds with claimed beneficial effects. Eisenia bicyclis (Aramé) and Porphyra tenera (Nori) are edible seaweeds which were previously recognized as rich in bioactive compounds. In the present study, we aim to evaluate the anti-hypercholesterolemia effect of these two seaweeds ex-tracts and their health potential. Both extracts, but more efficiently Aramé extract demonstrated to have liver 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitory activity and to reduce approximately 30 % cholesterol permeation through human Caco-2 cells simulating the intestinal lining, targets for hypercholesterolemia treatments. An untargeted metabolomic assay on human intestinal Caco-2 and liver Hep-G2 cells lines exposed to Aramé and Nori extracts revealed changes in the cell’s metabolism as indicators of the extract’s health beneficial effects. The metabolic pathways affected by exposure to both extracts were associated to lipid metabolism, such as phospholipids, and fatty acid metabolism, pathways of amino acid, cofactors and vitamins and cellular respiration metabolism. More profound for Aramé treated cells, but also seen for Nori ex-posed cells, the metabolites modifications were associated with the protection against CVDs and other diseases and, to the improvement of cells oxidative stress tolerance. The results obtained for the anti-hypercholesterolemia properties, in addition to the revelation of the positive impact on cells metabolism, are an important contribution for further evaluation of these seaweeds extracts as functional foods or for CVDs prevention.

Chickpea is an essential legume, a staple food in many cultures and contains nutrients with potential health benefits. The chickpea water (CPW) leached out after cooking is usually discarded, which may potentially have significant anti-cancer and other health beneficial properties. This study compared the in-vitro bioactivity of CPW with chickpea polyphenol extract (CPPE) to evaluate its impact on pathways of colorectal cancer progression and development. Morphological observation by APOPercentage, cell viability detection using a cytotoxic assay and cell migration-scratch assay points to measure rate of metastasis were employed. Overall antioxidant activity of CPW and CPPE were measured using ABTS and DPPH free-radical assays. At 50 µg/mL concentration and above, both CPW and CPPE extracts significantly reduce cell viability in HT-29 colon cancer cell lines (p < 0.05). Moreover, a quantitative analysis of the extent of apoptosis demonstrated that at 250 and 500 μg/mL concentrations, both extracts induced significant apoptosis compared to the untreated control. Meanwhile, the cell migration scratch area decreases by 34.42% and 15.27% when treated with CPW and CPPE, respectively. In summary, CPW demonstrated comparable in vitro anti-cancer properties and antioxidant activity in colorectal cancer cells to CPPE. Further, in vivo studies are warranted to evaluate the physiological bioactivity of CPW and CPPE in targeting pathways of cancer development and progression

Beta cells couple stimulation by glucose with insulin secretion and impairments in this coupling play a central role in diabetes mellitus. To clarify the effect of cAMP and the role of Epac2A in intracellular calcium signals and intercellular coupling, we performed functional multicellular calcium imaging in beta cells in mouse pancreas tissue slices after stimulation with glucose and forskolin in wild-type and Epac2A knock-out mice. Increased cAMP evoked calcium signals in otherwise sub-stimulatory glucose and beta cells from Epac2A knock-out mice displayed a faster activation. During the plateau phase, beta cells from Epac2A knock-out mice displayed a slightly higher active time in response to glucose compared with wild-type littermates, and increased cAMP increased the active time via a large increase in oscillation frequency and small decrease in oscillation duration in both Epac2A knock-out and wild-type mice. Functional network properties during stimulation with glucose did not differ in Epac2A knock-out mice, but the presence of Epac2A was crucial for the protective effect of increased cAMP in preventing a decline in beta cell functional connectivity with time. Finally, increased cAMP prolonged beta cell activity during deactivation in an Epac2A-independent manner.

Metastases cause high mortality in several cancers and immunotherapies are expected to be effective in the prevention and treatment of metastatic disease. However, only a minority of patients benefit from immunotherapies. This creates a need for novel therapies that are efficacious regardless of the cancer types and metastatic environments they are growing in. Preclinical immuno-oncology models for studying metastases have long been limited to syngeneic or carcinogenesis-inducible models that have murine cancer and immune cells. However, the translational power of these models has been questioned. Interactions between tumor and immune cells are often species-specific and regulated by different cytokines in mice and humans. For increased translational power, mice engrafted with functional parts of human immune system have been developed. These humanized mice are utilized to advance understanding the role of immune cells in the metastatic process, but increasingly also to study the efficacy and safety of novel immunotherapies. From these aspects, this review will discuss the role of immune cells in the metastatic process and the utility of humanized mouse models in immuno-oncology research for metastatic cancers, covering several models from the perspective of efficacy and safety of immunotherapies.

B-1 cells, a subtype of B lymphocytes, are found in lymphoid tissues and peritoneal and pleural cavities. They play diverse roles, releasing cytokines, generating antibodies, regulating the immune response, engaging in phagocytosis, and moving to inflammatory sites. However, their physiology remains partially understood, especially in stressful conditions like sleep restriction. This study aimed to investigate murine B-1 cell activation and differentiation under sleep restriction. Male C57BL/6J mice underwent an 18-hour sleep restriction for 21 days, followed by Candida albicans or Paracoccidioides brasiliensis infection. Purified peritoneal B-1 cells were evaluated for activation markers, microbicidal molecules, cytokine gene expression, Toll-like receptors, and commitment factors. Results showed that sleep restriction minimally influenced activation marker expression in B-1 cells across infection models. However, under sleep restriction, microbicidal molecule production increased in P. brasiliensis (NO) and C. albicans (ROS) infections. Gene expression revealed elevated TLR-2 and cytokines (IL-12, IL-6, TNF-α) in sleep-restricted animals. Lineage commitment analysis indicated myeloid polarization in sleep-restricted B-1 cells for all infection models. These findings underscore the impact of sleep restriction on B-1 cell activation and differentiation, with outcomes varying based on infection type. This study highlights the importance of investigating immunological changes resulting from sleep restriction.

Excessive activation of frog eggs, so called overactivation, can be initiated by strong oxidative stress, leading to expedited calcium-dependent non-apoptotic cell death. Overactivation also occurs spontaneously, albeit with a low frequency, in natural populations of spawned frog eggs. Currently, cytological and biochemical events of the spontaneous process are not characterized. In the present study, we demonstrate that spontaneous overactivation of Xenopus frog eggs, similarly to oxidative stress- and mechanical stress-induced overactivation, is characterized by the fast and irreversible contraction of the egg’s cortical layer, increase in the egg size, depletion of intracellular ATP, drastic increase in the intracellular ADP/ATP ratio, and degradation of M phase-specific cyclin B2. These events manifest in eggs in the absence of caspase activation within just one hour of triggering overactivation. Importantly, large amounts of ATP and ADP leak from the overactivated eggs, indicating that plasma membrane integrity is compromised in these cells. The rapture of the plasma membrane and acute depletion of intracellular ATP define explicitly necrotic cell death. Finally, we report that egg overactivation can occur in the frog’s genital tract. Our data argue that mechanical stress may be a key factor promoting egg overactivation during natural spawning in frogs.

Colony-stimulating factor 1 receptor (CFS-1R) is a myeloid receptor with a crucial role in monocyte survival and differentiation. Its overexpression is associated with aggressive tumor characterized by an immunosuppressive microenvironment and poor prognosis. CSF-1R ligands, IL-34 and M-CSF, are produced by many cells in the tumor microenvironment (TME), suggesting a key role for the receptor in the crosstalk between tumor, immune and stromal cells in the TME. Recently, CSF-1R expression was reported at the cell membrane of cancer cell from different solid tumors, capturing the interest of various research group interested in investigating the role of this receptor in non-myeloid cells. This review summarizes current data available on the expression and activity of CSF-1R in different tumor types. Notably, CSF-1R+ cancer cells have been shown to produce CSF-1R ligands, indicating that CSF-1R signaling is positively regulated in autocrine manner in cancer cells. Recent research demonstrated that CSF-1R signaling enhances cell transformation by supporting tumor cell proliferation, invasion, stemness and drug resistance. In addition, this review covers recent therapeutic strategies, including monoclonal antibodies and small molecule inhibitors, targeting the CSF-1R and designed to block the pro-oncogenic role of CSF-1R in cancer cell.

In this paper, we redefine the boundaries of blood cell classification, expanding from 5 to 11 distinct blood cell types using the challenging 11-class PBC dataset. This shift enables a deeper understanding of blood cell diversity, overcoming previous limitations in medical image analysis. Our approach combines state-of-the-art deep learning techniques, including pre-trained ConvNets, ViTb16 models, and custom CNN architectures. We employ transfer learning, fine-tuning, and ensemble strategies, such as CBAM and Averaging ensembles, to achieve unprecedented accuracy and interpretability. Our fully fine-tuned EfficientNetV2 B0 model sets a new standard, with a macro-average precision, recall, and F1-score of 91%, 90%, and 90%, respectively, and an average accuracy of 93%. This breakthrough underscores the transformative potential of 11-class blood cell classification for more precise medical diagnoses. Moreover, our groundbreaking "Naturalize" augmentation technique produces remarkable results. The 2K-PBC dataset generated with "Naturalize" boasts a macro-average precision, recall, and F1-score of 97%, along with an average accuracy of 96% when leveraging the fully fine-tuned EfficientNetV2 B0 model. This innovation not only elevates classification performance but also addresses data scarcity and bias in medical deep learning. Our research marks a paradigm shift in blood cell classification, enabling more nuanced and insightful medical analyses. The "Naturalize" technique’s impact extends beyond blood cell classification, emphasizing the vital role of diverse and comprehensive datasets in advancing healthcare applications through deep learning.

The cell surface targeting of neo-synthesized G protein coupled receptors (GPCRs) involves recruitment of receptor into COPII vesicles budding at Endoplasmic Reticulum Exit sites (ERES). This process is regulated for some GPCRs by escort proteins, which facilitate their export, or by gatekeepers that retain the receptors in the ER. PRAF2, an ER gatekeeper of the heterodimeric GABAB receptor protomer GB1, which interacts with a tandem di-leucine / RXR retention motif in the carboxyterminal tail of GB1, also inhibits the plasma membrane export of the chemokine receptor CCR5. PRAF2 / CCR5 interactions involve the transmembrane domains of both proteins. The di-leucine / RXR motif contained in the third intracellular loop of CCR5 does not affect PRAF2-mediated retention but impairs instead the interaction between CCR5 and its private escort protein CD4. PRAF2 and CD4 thus display opposite roles on the cell surface export of CCR5, likely at the level of its recruitment into COPII vesicles, PRAF2 inhibiting and CD4 promoting this process.

We conducted a retrospective analysis of the immunohistochemical (IHC) staining GRP94, an ER stress protein on large B-cell lymphoma (LBCL) cells, intracellular p53, and 15 factors involved in the metabolism of CHOP regimen :AKR1C3 (HO-metabolism), CYP3A4 (CHOP-metabolism) and HO efflux pumps (MDR1, MRP1). The study subjects were 42 patients with LBCL at our hospital. IHC staining using antibodies against the 17 factors. The odds ratios by logistic regression analysis using a dichotomous variable of CR, non-CR/relapse were statistically significant: for MDR1, MRP1, and AKR1C3. The overall survival (OS) after R-CHOP was compared by the log-rank test. The four groups showed that Very good (5-year OS, 100%) consisted of 4 patients showed negative IHC staining for both GRP94 and CYP3A4. Very poor (1-year OS, 0%), consisted of 3 patients who showed positive results of IHC for both GRP94 and CYP3A4. The remaining 35 patients comprised two subgroups: Good (5-year OS 60-80%.): 15 patients who showed negative staining for both MDR1 and AKR1C3, Poor: 5-year OS, 10-20%) :20 patients who showed positive staining for either MDR, AKR1C3,,MRP1 or p53. The Histological Prognostic Index (HPI) (The four groups: Very poor, Poor, Good, and Very pood) is a breakthrough method for stratifying patients based on factors involved in the development of treatment resistance.

The influence of preoperative examination of oral squamous cell carcinoma (OSCC) mucosal surrounding by VELscope (Visually Enhanced Lesion Scope) on the radicality of surgical treatment of OSCC was the goal of this study.It is the first analysis of its kind with a total number of 122 patients suffering from OSCC with homogenous distribution of different tumor stages randomized into a study and a control group and enrolled in our study after meeting the inclusion criteria. The preoperative checkup by VELscope accompanied by the marking of the range of a loss of fluorescence in the study group was performed before the surgery. We have developed a unique mucosal tattoo marking technique for this purpose. The pathohistological results after surgical treatment, i.e. the margin status, were then compared. We achieved the pathological free margin (pFM) in 55 patients, the pathological close margin (pCM) in 6 cases and we encountered no case of the pathological positive margin (pPM) in the mucosal layer in the study group. In comparison, the control group results revealed pPM in 7 cases, pCM in 14 cases and pFM in 40 of all cases in the mucosal layer. This study proved that the preoperative autofluorescence evaluation of a tumor mucosal surrounding can enhance the ability to reach the pFM resection.

Cell-free massive multiple input multiple output (MIMO) has the potential of providing joint services including joint initial access, efficient clustering of access points (APs) and pilot allocation to user equipments (UEs) over large coverage area with reduced interference. In cell-free massive MIMO, large coverage area corresponds to provision and maintenance of scalable quality of service requirements for infinitely large number of UEs. The research in cell free massive MIMO is mostly focused on time division duplex mode due to availability of channel reciprocity which aids in avoiding feedback overhead. However, frequency division duplex (FDD) protocol still dominates the current wireless standards and the provision of angle reciprocity aids in reducing this overhead. The challenge of providing a scalable cell-free massive MIMO system in FDD setting is also prevalent, since computational complexity regarding signal processing tasks such as channel estimation, precoding/combining and power allocation, becomes prohibitively high with increase in number of UEs. In this work, we consider an FDD based scalable cell-free network with angular reciprocity and dynamic cooperation clustering approach. We have proposed scalability for our FDD cell-free and perform comparative analysis with reference to channel estimation, power allocation and precoding/combining techniques. We present expressions for scalable spectral efficiency, angle based precoding/combining schemes and provide comparison of overhead between conventional and scalable angle based estimation as well as combining schemes. Simulations confirm that the proposed scalable cell-free network based on FDD scheme outperforms the conventional matched filtering scheme based on non-scalable precoding/combiming schemes. The angle based LP-MMSE in FDD cell-free network provides 14.3% improvement in spectral efficiency and 11.11% improvement in energy efficiency compared to non-scalable MF scheme.

Cell monolayers, including endothelial and epithelial cells, play crucial roles in regulating the transport of biomolecules to underlying tissues and structures via intercellular junctions. Moreover, the monolayers form a semipermeable barrier across which leukocyte transmigration is tightly regulated. The inflammatory cytokines can disrupt the epithelial and endothelial permeability, thus the reduced barrier integrity is a hallmark of epithelial and endothelial dysfunction related with numerous pathological conditions, including cancer-related inflammation. Therefore, the assessment of barrier function is critical in in vitro models of barrier-forming tissues. This review summarizes the commercially available in vitro systems used to measure the permeability of cellular monolayers. The presented techniques are separated in two large groups: macromolecular tracer flux assays, and electrical impedance measurement-based permeability assays. The presented techniques are briefly described and compared.

Previous evidence links the formation of extranuclear inclusions of transcription factors, such as ERK, Jun, TDP-43, and REST with oxidative, endoplasmic-reticulum, proteasomal, and osmotic stress. To further characterize its extranuclear location, we performed a high-content screening based on confocal microscopy and automatized image analyses of an epithelial cell culture treated with hydrogen peroxide, thapsigargin, epoxomicin, or sorbitol at different concentrations and times to recreate the stresses mentioned above. We also performed subcellular fractionation of the brain from transgenic mice overexpressing the Q331K mutated TARDBP, and we analyzed REST-regulated mRNAs. The results show that these nuclear proteins exhibit a mitochondrial location, together with significant nuclear/extranuclear ratio changes, in a protein and stress-specific manner. The presence of these proteins in enriched mitochondrial fractions in vivo confirmed the results of image analyses. TDP-43 aggregation was associated with alteration in mRNA levels of REST target genes involved in calcium homeostasis, apoptosis, and metabolism. In conclusion, cell stress increased mitochondrial translocation of nuclear proteins, increasing the chance of proteostasis alterations. Further, TDP-43 aggregation impacts REST target genes, disclosing an exciting interaction between these two transcription factors in neurodegenerative processes.

A distinctive feature of the SARS-CoV-2 spike protein is its ability to efficiently fuse cells, thus producing syncytia found in COVID-19 patients. This commentary proposes how this ability enables spike to cause COVID-19 complications as well as side effects of COVID-19 vaccines, and suggests how these effects can be prevented..

One of the important research directions in the field of photovoltaics is integration with construction. The integration of solar cell systems with a building can reduce installation costs and help optimize the used space. One of the interesting types of cells is dye-sensitized solar cells. In addition to their interesting properties, they also have aesthetic value. In the classic arrangement, they are constructed using glass with a transparent conductive layer (TCL). This article describes replacing a classic glass counter electrode with an electrode based on a ceramic tile and nickel foil. This solution makes it possible to expand their construction applications. The advantage of this solution is full integration with construction while simultaneously generating electricity. A dye-sensitized solar cell was built layer-by-layer on ceramic tile and nickel foil. An atomization method was used to deposit fluorine-doped tin oxide, and then a screen printing method was used to deposit a platinum layer. The electrical parameters of the manufactured DSSCs with and without a counter electrode tile were characterized by measuring their current-voltage characteristics under standard AM 1.5 radiation. A dye-sensitized solar cell integrated with ceramic tiles and nickel foil was produced and displayed an efficiency of over 4%.

Diffuse large B cell lymphoma (DLBCL) is curable with chemoimmunotherapy in ~65% of patients. One of the hallmarks of the pathogenesis and resistance to therapy in DLBCL is inhibition of apoptosis, which allows malignant cells to survive and acquire further alterations. Inhibition of apoptosis can be the result of genetic events inhibiting the intrinsic or extrinsic apoptotic pathways, as well as their modulators, such as the inhibitor of apoptosis proteins, P53, and components of the NF-kB pathway. Mechanisms of dysregulation include upregulation of anti-apoptotic proteins and downregulation of pro-apoptotic proteins via point mutations, amplifications, deletions, translocations, and influences of other proteins. Understanding the factors contributing to resistance to apoptosis in DLBCL is crucial in order to be able to develop targeted therapies that could improve outcomes by restoring apoptosis in malignant cells. This review describes the genetic events inhibiting apoptosis in DLBCL, provides a perspective of their interactions in lymphomagenesis, and discuss their implication for the future of DLBCL therapy.

Activation of the NLRP3 inflammasome plays a crucial role in innate immune response. During cell division, the NLRP3 inflammasome activation must be strictly controlled. Here, we discovered the anaphase promoting complex subunit 10 (Anapc10, APC10), a substrate recognition protein of the anaphase promoting complex/cyclosome (APC/C), is a critical mediator of the NLRP3 inflammasome activation. APC10 protein interacts with NLRP3, and co-localizes with NLRP3 protein in the cytoplasm. During interphase, APC10 interacts with NLRP3 to promote the NLRP3 inflammasome activation. During mitosis, APC10 disassociates from the NLRP3 inflammasome to inhibit the inflammatory responses. This study reveals a distinct mechanism by which APC10 serves as a switch of the NLRP3 inflammasome activation during cell cycle.

The thymus hosts the development of a specific type of adaptive immune cells called T cells. T cells orchestrate the adaptive immune response through recognition of antigen by the highly variable T-cell receptor (TCR). T-cell development is a tightly coordinated process comprising lineage commitment, somatic recombination of Tcr gene loci and selection for functional, but non-self-reactive TCRs, all interspersed with massive proliferation and cell death. Thus, the thymus produces a pool of T cells throughout life capable of responding to virtually any exogenous attack while preserving the body through self-tolerance. The thymus has been of considerable interest to both immunologists and theoretical biologists due to its multiscale quantitative properties, bridging molecular binding, population dynamics and polyclonal repertoire specificity. Here, we review mathematical modelling strategies that were reported to help understand the flexible dynamics of the highly dividing and dying thymic cell populations. Furthermore, we summarize the current challenges to estimating in vivo cellular dynamics and to reaching a next-generation multiscale picture of T-cell development.

Turner syndrome (TS) is a chromosomal disorder that is caused by a missing or structurally ab-normal second sex chromosome. Subjects with TS are at an increased risk of developing intrauterine growth retardation, low birth weight, short stature, congenital heart diseases, infertility, obesity, dyslipidemia, hypertension, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular diseases (stroke and myocardial infarction). The underlying pathogenetic mechanism of TS is unknown. The assumption that X chromosome-linked gene haploinsufficiency is associated with the TS phenotype is questioned since such genes have not been identified. Thus, other pathogenic mechanisms have been suggested to explain this phenotype. Morphogenesis encompasses a series of events that includes cell division, the production of migratory precursors and their progeny, differentiation, programmed cell death, and integration into organs and systems. The precise control of the growth and differentiation of cells is essential for normal development. The cell cycle frequency and the number of proliferating cells are essential in cell growth. 45,X cells have a failure to proliferate at a normal rate, leading to a decreased cell number in a given tissue during organogenesis. A convergence of data indicates an association between a prolonged cell cycle and the phenotypical features in Turner syndrome. This review aims to examine old and new findings concerning the relationship between a prolonged cell cycle and TS phenotype. These studies reveal a diversity of phenotypic features in TS that could be explained by reduced cell proliferation. The implications of this hypothesis for our understanding of the TS phenotype and its pathogenesis are discussed. It is not surprising that 45,X monosomy leads to cellular growth pathway dysregulation with profound deleterious effects on both embryonic and later stages of development. The prolonged cell cycle could represent the beginning of the pathogenesis of TS, leading to a series of phenotypic consequences in embryonic/fetal, neonatal, pediatric, adolescence, and adulthood life.

The COVID-19 pandemic caused by SARS-COV-2 has infected over 500,000 people causing over 25,000 deaths in the last 10 weeks. A key host cellular protein required for the virus entry is angiotensin-converting enzyme 2 (ACE2). Recent studies have reported that patients with hypertension and diabetes treated with ACE inhibitors or angiotensin receptor blockers might be at a higher risk of COVID-19 infection as these drugs have been reported to increase ACE2 expression. This has raised the need to systematically investigate the effect of different drugs including antihypertensives on modulating ACE2 expression. Here, we analyzed a publicly available CMAP dataset of pre/post transcriptomic profiles for drug treatment in cell lines for over 20,000 small molecules. We show that only one subclass of antihypertensives drugs - ACE inhibitors, are significantly enriched for drugs up-regulating ACE2 expression. Studying the effects of the 672 clinically approved drugs in CMAP, we chart the drug categories that affect ACE2 expression. Specifically, we find that panobinostat (an HDAC inhibitor) confers the highest up-regulation of ACE2 expression while isotretinoin (a vitamin A derivative) is its strongest down-regulator. Our results provide initial candidates guiding further in vitro and in vivo studies aimed at assessing drug effects on ACE2 expression.

In order to reach the theoretical efficiency limits of lead-based metal halide perovskite solar cells, the voltage should be enhanced because it suffers from nonradiative recombination. Perovskite materials contain intrinsic defects that can act as Shockley-Read-Hall recombination centers. Several experimental and computational studies have characterized such defect states within the band gap. We give a systematic overview of compositional engineering by distinguishing the different defect reducing mechanisms. Doping effects are divided into influences on: (1) Crystallization; (2) Lattice properties. Incorporation of dopant influences the lattice properties by: (a) Lattice strain relaxation; (b) Chemical bonding enhancement; (c) Band gap tuning. The intrinsic lattice strain in undoped perovskite was shown to induce vacancy formation. The incorporation of smaller ions, such as Cl, F and Cd, increases the energy for vacancy formation. Zn doping is reported to induce strain relaxation but also to enhance the chemical bonding. The combination of computational studies using (DFT) calculations quantifying and qualifying the defect reducing propensities of different dopants with experimental studies is essential for deeper understanding and unraveling insights, such as the dynamics of iodine vacancies and the photochemistry of the iodine interstitials, and can eventually lead to a more rational approach in the search for optimal photovoltaic materials.

Durability and performance of electrochemical energy converters such as fuel cells and electrolysers are not only dependent on the properties and the quality of the used materials. They strongly depend on operation conditions. Variations in external parameters, such as flow, pressure, temperature and, obviously, load can lead to significant local changes of current density, even local transients. The segmented cell technology was developed with the purpose to gain insight into local operation conditions in electrochemical cells, during operation. The operando measurement of the local current density and temperature distribution allows effective improvement of operation conditions, mitigation of potentially critical events and assessment of the performance of new materials. The segmented cell, which can replace a regular bipolar plate in the current state of the technology, can be used as monitoring tool and for targeted developments. This article gives an overview over the development and applications for proton exchange membrane fuel cell of this technology, such as water management or fault recognition. Recent advancements towards locally resolved monitoring of humidity and to current distributions in electrolysers are outlined.

Bio-devices are designed to allow biological matter to perform in vitro almost the same functions it performs in vivo. Therefore, they can benefit from the specificities of such materials and are expected to perform better than traditional devices. On the other hand, the integration of biological material with electronic/electrochemical instrumentation requires careful attention and can produce unconventional results. In this paper, we describe the impedance response of an electrochemical cell that converts sunlight into electrical power. It uses the photosynthetic system known as Reaction Center, which is the core of photosynthesis in several living beings. Under illumination, an abrupt transformation drives the cell electrical response from insulator to conductor and a photocurrent is observed. The impedance spectrum shows a peculiar shape which significantly modifies with the protein activation. It has been analyzed by means of a graphical/analytical/ numerical procedure. The modelling identifies an analogue electrical circuit, whose parameters give quantitative information about the underlying process. Finally, an appropriate normalization of data is proposed which validates data in dark and light and can be useful as a fast screening of measurements.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating illness whose biomedical basis is now beginning to be elucidated. We reported previously that, after recovery from frozen storage, lymphocytes (peripheral blood monocytic cells, PBMCs) from ME/CFS patients die faster in culture medium than those from healthy controls. We also found that lymphoblastoid cell lines (lymphoblasts) derived from these PBMCs exhibit multiple abnormalities in mitochondrial respiratory function and signalling activity by the cellular stress-sensing kinase TORC1. These differences were correlated with disease severity, as measured by the Richardson and Lidbury Weighted Standing Test. The clarity of the differences between these cells derived from ME/CFS patient blood and those from healthy controls suggested that they may provide useful biomarkers for ME/CFS. Here we report a preliminary investigation into that possibility using a variety of analytical classification tools, including linear discriminant analysis, logistic regression and Receiver Operating Characteristic (ROC) curve analysis. We found that results from three different tests, lymphocyte death rate, mitochondrial respiratory function and TORC1 activity could each individually serve as biomarker with better than 90% sensitivity but only modest specificity vís a vís healthy controls. However, in combination they provided a cell-based biomarker with sensitivity and specificity approaching 100% in our sample. This level of sensitivity and specificity was almost equalled by a suggested protocol in which the frozen lymphocyte death rate was used as a highly sensitive test to triage positive samples to the more time consuming and expensive tests measuring lymphoblast respiratory function and TORC1 activity. This protocol provides a promising biomarker that could assist in more rapid and accurate diagnosis of ME/CFS.

Excessive cell phone use contributes to distracted driving, may increase risk for automobile accidents, and a minority of mobile phone users exhibit behaviors consistent with technological addiction. The purpose of this study was to determine whether cell phone beliefs and behaviors could be changed by a brief educational encounter. The Theory of Reasoned Action provided a lens for viewing attitudes and behavior. A one-week pre-post design with a thirty-day follow-up was used with participants (N = 215, 67.0% female, age = 20.0 + 1.6) assigned to a peer led intervention or comparison groups. The intervention included cell-phone educational materials. A short index of cell phone behavior was developed which showed good internal consistency with a Cronbach’s alpha of .81. The intervention group “agreed” or “strongly-agreed” more than the comparison group on five of the seven areas of cell phone beliefs and behaviors ( p < 0.05, item Cohen’s d = .32 to .47, total d = .50) at one-week following receipt of informational materials. We conclude that attitudes and behaviors regarding cell phones are malleable and susceptible to change in young-adults following a brief psychoeducational intervention.

It is well known that the major constrain to the efficiency of photovoltaic (PV) devices comes from the generation of unused heat. In this context, thermoelectric generators have been proposed as a viable heat recovery solution, leading to an increase of the overall efficiency. Within this kind of hybrid solutions, the PV and TEG parts can be either electrically separated or connected in the same circuit. In the second case, the presence of the TEG in series to the PV cell can lead to electrical losses. In this work we analyze the effect of various parameters on the output power of electrically hybridized HTEPV systems by means of both electrical measurements and simulations. The results reveal that while electrical lossless condition exists (as also reported in previous work) it not always corresponds to significant power gains respect with the sole PV case. In addition, the strong temperature sensitivity of the lossless condition makes the electrical hybridization hardly practically implementable. This sensitivity in the framework of an actual application scenario, where the solar radiation is variable over time, would make the system working often in a suboptimal regime. The present study gives a new understanding on the actual applicability of electrically hybridized HTEPV devices.

Morphogenesis remains a riddle, wrapped in a mystery, inside an enigma. It remains a formidable problem viewed from many different perspectives of morphology, genetics, and computational modelling. We propose a biochemical reductionist approach that shows how both internal and external physical forces contribute to plant morphogenesis via mechanical stress-strain transduction from the primary cell wall tethered to the plasma membrane by a specific arabinogalactan protein (AGP). The resulting stress vector with direction defined by Hechtian adhesion sites, has a magnitude of a few picoNewtons amplified by a hypothetical Hechtian growth oscillator. This paradigm shift involves stress activated plasma membrane Ca2+channels and auxin-activated H+-ATPase. The proton pump dissociates periplasmic AGP-glycomodules that bind Ca2+. Thus, as the immediate source of cytosolic Ca2+ an AGP-Ca2+ capacitor directs vectorial exocytosis of cell wall precursors and auxin efflux (PIN) proteins. In toto these components comprise the Hechtian Oscillator and also the gravisensor. Thus interdependent auxin and Ca2+ morphogen gradients account for the predominance of AGPs. The size and location of a cell surface AGP-Ca2+ capacitor is essential to differentiation and explains AGP correlation with all stages of morphogenetic patterning from embryogenesis to root and shoot. Finally, evolutionary origins of the Hechtian Oscillator in the unicellular Chlorophycean algae reflect the ubiquitous role of chemiosmotic proton pumps that preceded DNA at the dawn of life.

In recent years, bone tissue engineering (BTE) has made significant progress in promoting the direct and functional connection between bone and graft, including osseointegration and osteoconduction, to facilitate the healing of damaged bone tissues. Herein, we introduce a new, environmentally friendly, and cost-effective method for synthesizing reduced graphene oxide (rGO) and hydroxyapatite (HAp). The method uses epigallocatechin-3-O-gallate (EGCG) as a reducing agent to synthesize rGO (E-rGO), and HAp powder is obtained from Atlantic bluefin tuna (Thunnus thynnus). The physicochemical analysis indicated that the E-rGO/HAp composites had exceptional properties for use as BTE scaffolds, as well as high purity. Moreover, we discovered that E-rGO/HAp composites facilitated not only proliferation, but also early and late osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our work suggests that E-rGO/HAp composites may play a significant role in promoting the spontaneous osteogenic differentiation of hMSCs, and we envision that the E-rGO/HAp composites could serve as promising candidates for BTE scaffolds, stem cell differentiation stimulators, and implantable device components due to their biocompatible and bioactive properties. Overall, we suggest a new approach for developing cost-effective and environmentally friendly E-rGO/HAp composite materials for BTE application.

Some biostimulants, including plant origin preparations, act similarly to plant hormones. Moreover, the supplementation of known and unknown rooting cofactors can stimulate rhizogenesis in cuttings. The aim of this research was to assess the response of difficult-to-root and long-rooting stem cuttings of the once-blooming old variety Rosa ‘Hurdal’ to preparations of plant origin. The hypothesis was that plant origin preparations could enhance rooting processes by inhibiting chlorophyll a/b degradation in leaves and postponing leaf senescence, simultaneously increasing the quality of cuttings. The one-bud stem cuttings were made in four phenological stages: (H1) flower buds closed, (H2) open flowers, (H3) just after petal fall, (H4) 7-14 days after petal shedding. They were treated with either standard commercial powder preparations containing 0.4% indolebutyric acid (IBA) or 0.2% naphthalene acetic acid (NAA) as well as with commercial plant origin preparations that this work will henceforth refer to as: Algae Extract, Organic Preparation, and Plant Extract. The cuttings were evaluated after 12 weeks of rooting them in two substrates: peat-perlite and peat-sand (v:v; 1:1). Mean root percentages for both substrates were noted after preparation from stage H1 (74.5 %), H2 (59.5 %), H3 (50.8 %) shoots. The H4 cuttings didn’t root at all and were not considered further. The means for all phenology stages together were the highest by the use of 0.6 % Algae Extract, 0.012 % and 0.02 % Organic Preparation, 0.2 % and 0.4 % Plant Extract. The lowest means were reported for the control cuttings as well as NAA and IBA treatment. Plant origin preparations encouraged growth parameters but did not unequivocally inhibit the decrease of chlorophyll content in the cuttings’ leaves. Rooting percentage depended on the quality of cuttings as well as chlorophyll a/b and soluble protein content in leaves in both rooting substrates.

Bone tissue engineering has developed significantly in recent years as the increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.

Visceral Leishmaniasis is a neglected tropical disease affecting 12 million people annually. Even in the second decade of the 21st century, it has remained without an effective vaccine for human use. In the current study, we have designed three multiepitope vaccine candidates by the selection of multiple IFN-γ inducing MHC-I and MHC-II binder T-cell specific epitopes from 3 previously identified antigen genes of Leishmania donovani from our lab, by immune-informatic approach using IFNepiotpe, NET-MHC-1 and NET MHC-2 webservers. We have tested the protective potential of these three multiepitope proteins as vaccine in a hamster model of visceral leishmaniasis. The immunization data revealed that the vaccine candidates induced a very high level of Th-1 biased protective immune response in-vivo in a hamster model of experimental visceral Leishmaniasis, with one of the candidates inducing a sterile immunity. The vaccinated animals displayed highly activated monocyte macrophages with the capability of clearing intracellular parasites due to increased respiratory burst. Additionally, these proteins induced activation of polyfunctional T cells secreting INF-γ, TNF-α, and IL-2 in ex-vivo stimulation of human peripheral blood mononuclear cells, further supporting the protective nature of designed candidates.

Post-acute COVID-19 vaccination syndrome (PACVS) is distinguished from the normal post-vaccination state by altered receptor antibodies (Semmler et al. Vaccines 2023, 11, 1642). Here, we explore the symptoms registry and standard serum markers acquired in the above study to delineate the disease phenotype of PACVS. Symptoms reported by the participants overlapped with established complex dysautonomia syndromes (ME/CFS, POTS, MCAS, SFN). However, many participants were qualified for several (131/191) or none (31/191) of these syndromes. Unbiased clustering (modified Jaccard index) revealed a prevalent cross-cohort symptomatology of malaise and chronic fatigue (&gt; 80% of cases). Overlapping clusters of (i) peripheral nerve dysfunction, dysesthesia, motor weakness, pain, vasomotor dysfunction, (ii) cardiovascular impairment, and (iii) cognitive impairment, headache, optic, oculo-motoric and acoustic dysfunctions were also frequently represented. Conspicuous serum markers encompassed increases in interleukins 6 and 8 and low fT3 levels (&gt; 80%), IgG-subclass imbalances and impaired iron-storage (&gt; 50%), and increases in sNFL (&gt; 30%). Serum markers were not correlated to specific symptoms or symptom clusters. A single and unique cause (i. e. SARS-CoV-2 vaccination) is improbable to trigger several distinct etiologies. Therefore, the symptoms and serological features observed in our study cohort probably represent facets of a single complex syndrome.

Inertial focusing based Lab-on-Chips represent nowadays a promising technology for cell sorting in various applications, thanks to their coherence with the ASSURED criteria recommended by the World Health Organization, being: Affordable, Sensitive, Specific, User-friendly, Rapid and Ro-bust, Equipment-free and Delivered. Inertial focusing in spiral microchannel can offer a rapid, portable and ease of prototyping solution for cell-sorting. In literature, different geometries of microfluidic channel have been investigated to understand how hydrodynamic forces, due to primary and secondary flow, influence particle focusing. The balancing of these forces in spiral microchannels allows for high throughput and filtration efficiency across different particle and sizes. The understanding of such mechanism represents a key aspect to address the prototyping of spiral devices for the target application. A clear, complete and orderly overview in the current literature is lacking. For this reason, we aim to compare the main features of inertial focusing depending on various cross-section (rectangular, trapezoidal, triangular, hybrid) in spiral devices. Additionally, details about materials and prototyping techniques will be provided. This review study will provide readers a comprehensive overview of current research, guiding future ex-perimentation by expediting the selection of spiral geometries and materials based on the type of particle to be separated.

Bladder cancer (BC) is one of the most lethal genitourinary malignancies owing to its propensity for recurrence and poor survival. The biochemical pathway, signal transducer and activator of transcription 3 (STAT3), has gained significance as a molecular pathway that promotes proliferation, invasion, and chemoresistance. In this study, we explored the targeting of STAT3 with TTI-101 and SH5-07 in bladder cancer (BCa) and elucidated the mechanisms in three-dimensional (3D) spheroid and tumoroid models. We optimized the growth of spheroids from human, rat, and mouse BCa cell lines (J82, NBT-II, and MB49, respectively), and tumoroids from BBN (N-butyl-N-(4-hydroxybutyl)-nitrosamine) induced rat bladder tumors. Cell viability was assessed using MTT and trypan blue assays. ATP production, ROS production, and calcium AM (CA)/EtBr staining were used to measure the spheroid and organoid inhibition and mitochondrial function. Western blot analysis was performed to evaluate the pharmacodynamic markers involved in cell proliferation, apoptosis, cancer stem cells (CSCs), and STAT3 signaling in BCa. We found that targeting STAT3 (using TTI-101 and SH5-07) significantly reduced the proliferation of BCa spheroids, and tumoroids, which was accompanied by decreased expression of pSTAT3, Cyclin D1, and PCNA. Our data also demonstrated that treatment with STAT3 inhibitors induced ROS production and cell death in BCa spheroids and organoids. STAT3 inhibition induced cell death was associated with the activation of caspase 3/7 and PARP cleavage. Moreover, TTI-101 and SH5-07 targets cancer stem cells by downregulating the expression of CD44 and CD133 in 3D models. This study provides the first evidence for the prevention of bladder cancer with small-molecule inhibitors TTI101 and SH5-07 via suppression of CSCs and STAT3 signaling.

Chimeric antigen receptor (CAR) T-cell therapy has greatly improved outcomes for patients with relapsed or refractory hematological malignancies. However, challenges such as treatment resistance, relapse, and severe toxicity still hinder its widespread clinical application. Traditional transcriptome analysis has provided limited insights into the complex transcriptional landscape of both leukemia cells and engineered CAR-T cells, as well as their interactions within the tumor microenvironment. However, with the advent of single-cell sequencing techniques, a paradigm shift has occurred, providing robust tools to unravel the complexities of these factors. These techniques enable unbiased analysis of cellular heterogeneity and molecular patterns. These insights are invaluable for precise receptor design, guiding gene-based T cell modification, and optimizing manufacturing conditions. Consequently, this review utilizes modern single-cell sequencing techniques to clarify the transcriptional intricacies of leukemia cells and CAR-Ts. The aim of this manuscript is to discuss the potential mechanisms that contribute to the clinical failures of CAR-T immunotherapy. We will examine the biological characteristics of CAR-Ts, the mechanisms that govern clinical responses, and the intricacies of adverse events. By exploring these aspects, we hope to gain a deeper understanding of CAR-T therapy, which will ultimately lead to improved clinical outcomes and broader therapeutic applications.

Watermelon fruits of different ploidy exhibit significant variations in texture. In order to investigate the primary factors influencing texture differences, this study was conducted to investigate the differences in fruit texture development using homozygous autogamous diploid (2X)lines and their autotriploid (3X) and autotetraploid (4X) lines 'Yixuan'. The research encompassed fruit development, flesh texture profile analysis (TPA), flesh cell wall polysaccharide content, and flesh cell microstructure analysis, specifically in 2X, 3X, and 4X watermelon fruits.The results showed that as watermelon fruits matured, several characteristics exhibited an ascending trend, including fruit weight, TSS (total soluble solids) content, rind hardness, flesh cell size, and cell wall polysaccharide contents such as crude fiber, cellulose, hemicellulose, lignin, and protopectin. Conversely, the flesh texture parameters and soluble pectin content of the flesh cell wall gradually declined. Notably, significant differences in fruit flesh texture and flesh cell structure were observed among fruits of different ploidy at the 32d. Specifically, 2X fruits displayed considerably lower rind hardness, reduced flesh texture (Hardness, Fracturability, Chewiness, Gumminess), and cell density compared to 3X and 4X fruits. Additionally, 2X fruits exhibited larger cell sizes than 3X and 4X fruits. However, no significant differences were observed in the content of flesh cell wall polysaccharide contents across various ploidy levels.These findings suggested that the variation in texture among watermelon fruits of different ploidy can be attributed to the size and arrangement of flesh cells. Importantly, this research provided a foundation for further exploration of the intrinsic regulatory factors and molecular mechanisms contributing to texture variation in polyploid watermelon fruits.

REV-ERBα and its paralog, REV-ERBβ encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock that can be pharmacologically targeted to treat various circadian rhythm-related diseases, such as cardiometabolic, inflammatory, and neuropsychiatric diseases, as well as cancer. REV-ERBs are believed to be functionally redundant and compensatory, although they often affect the expression of gene subsets in an isoform-specific manner. Therefore, this study aimed to identify the redundant and distinct roles of each isoform in controlling its target genes by comparing the transcriptome profiles of a panel of mutant U2OS human osteosarcoma cells in which either NR1D1 or NR1D2 was ablated. Indeed, our transcriptomic analyses revealed that most REV-ERB-regulated genes were controlled by redundant or even additive actions. However, the RNA expression profiles of each single mutant cell line also provided strong evidence for isoform-dependent actions. For example, REV-ERBα were more responsible for regulating the NF-κΒ signaling pathway, whereas a group of extracellular matrix components required REV-ERBβ to maintain their expression. We found that REV-ERBs have isoform-selective functions in the regulation of certain circadian output pathways, despite their overlapping roles in the circadian molecular clock. Thus, the development of isoform-selective REV-ERB modulators may help treat metabolic disturbances and certain types of cancer.

Terrestrial algae are the group of photosynthetic organisms, which can survive in extreme conditions. pH is one of the most important factor, influencing on distribution of algae, both in aquatic and terrestrial ecosystems. The influence of different pH levels on cell volume and other morphological characters of authentic and reference strains of Chlorella vulgaris, Bracteacoccus minor, Pseudoccomyxa simplex, Chlorococcum infusionum, and Vischeria magna were studied. Chlorella vulgaris and Pseudoccomyxa simplex were the most resistant species, retaining its morphology in range of pH 4-11,5. The change of pH towards acidic and alkaline levels caused the increase of volume of Pseudoccomixa simplex and Vischeria magna cells according to polynomial regression model. Volume of Chlorella vulgaris cells increased from low to high pH according to linear regression model. Changes of pH levels did not have a significant impact on volume of Bracteacoccus minor and Chlorococcum infusionum cells. Low and high levels of pH caused thickening of cell walls of Chlorococcum infusionum and increase of oil containing substances in Vischeria magna and Bracteacoccus minor cells. Our study revealed a high resistance of studied species to extreme level of pH, which allow recommend these strains for broader use in biotechnology and natures protection.

Human keratinocytes and melanoma can stick together to form clusters after eight days in co-culture. As in dynamic system concepts, one can consider cluster formation as the system attractor, cell seeding as the initial condition, and density change over time as a path within the basin of attraction. Herein, Cellular Automata, which is a class of Agent-Based Models, and Boolean Networks are discrete modeling methods used in population dynamics such that running the dynamics of cellular automata backward reveals an underlying network in terms of basin of attraction, also known as global dynamics. Thus, we hypothesize that one can estimate the local dynamic of an agent-based model from the basin of attraction of a boolean network. Here, we propose an approach to estimating these agent-based model rules, which consists of comparing the density states within each state transition and reaching a consensus among state transitions belonging to a basin of attraction of a boolean network. The objectives of this study are: (1) to infer a boolean network from the co-culture growth curve; (2) to estimate the rules of agent-based models; and (3) to implement spatial dynamics simulations. The binarization of the growth curve shows high population density after four days; the estimated agent-based model rules were compatible with cell proliferation and migration in agreement with literature, so we had to propose individual rules for survival and death. Spatial dynamics shows that (1) keratinocytes exhibit a higher density in neighborhoods where melanoma is present; (2) the chance of keratinocyte migration increases until the fourth day, then decreases, and the probability of survival increases substantially after four days; and (3) cells with low proliferation capacity die and free space for those with high ones. Our approach suggests that the attractor state of cell co-culture is induced mainly by an increase in keratinocyte migration and survival. Our approach has the potential to offer valuable clues about microenvironmental interactions or configurations that drive population dynamics.

Peptidoglycan hydrolases are enzymes that cleave the peptidoglycan of the bacterial cell wall, facilitating cell growth, cell division, and peptidoglycan turnover. Xanthomonas citri subsp. citri (X. citri), the causal agent of citrus canker, encodes an Escherichia coli M23 peptidase EnvC homolog. EnvC is a LytM factor required for septal peptidoglycan splitting and daughter cell separation. In this study we investigate how EnvC contributes to the virulence and cell separation of X. citri. We observed that disruption of the X. citri envC gene (ΔenvC) led to a reduction in virulence. Upon inoculation into leaves of Rangpur lime (Citrus limonia Osbeck), the X. citri ΔenvC mutant showed a delay in causing citrus canker symptoms compared with the wild-type X. citri strain. Mutant complementation restored the X. citri wild type phenotype. Subcellular localization confirmed that X. citri EnvC is a periplasmic protein. Moreover, the X. citri ΔenvC mutant exhibited elongated cells, indicative of a cell division defect. These findings support the role of EnvC in regulating virulence, cell wall organization, and cell division in X. citri.

To the best of the author’s knowledge, studies of mature plasmacytoid dendritic cell proliferation associated with T lymphoblastic lymphoma were extremely rare in the literature. Here, we report a patient who underwent both mature plasmacytoid dendritic cell proliferation and T lymphoblastic lymphoma. With the findings of lymph node biopsy taken from the right cervical and inguinal regions, we identified eye-catching mature plasmacytoid dendritic cells that were considered to be responsible for this lesion at the beginning, until the immunostaining of Ki67 and TDT showed a small group of positive cells hiding in these plasmacytoid dendritic cells. Bone marrow biopsy was also performed in this patient. Microscopically, the hematopoietic tissue was almost completely replaced by lymphoblastoid cells with condensed chromatin, inconspicuous nucleoli and scanty cytoplasm, which were basically the same as those seen in the lymph nodes in morphology. However, there was no sign of plasmacytoid dendritic cells or Langerhans cells in the bone marrow biopsy. With the help of bone marrow biopsy, our final diagnosis of the lymph node was T lymphoblastic lymphoma coexisting with mature plasmacytoid dendritic cell proliferation . Although accumulations of plasmacytoid dendritic cells may occur in some infections or reactive lymphadenopathy, the presence of extensive nodules or infiltration of plasmacytoid dendritic cells strongly reminds the pathologist to carefully evaluate the bone marrow or peripheral blood status of the patient to exclude a hidden myeloid or other neoplasm.

Production of biofuel from lignocellulosic biomass is relatively low due to the limited knowledge about natural cell wall loosening and cellulolytic processes in plants. Industrial separation of cellulose fiber mass from lignin, its saccharification and alcoholic fermentation is still cost-ineffective and environmental unfriendly. Assuming that the green transformation is inevitable and that the new sources of raw materials for biofuels are needed, we decided to study cell death - a natural process occurring in plants in a context of reducing the recalcitrance of lignocellulose for production of second generation bioethanol. “members of the enzyme families responsible for lysigenous aerenchyma formation were identified during the root hypoxia stress in Arabidopsis thaliana cell death mutants. The cell death regulatory genes, LESION SIMULATING DISEASE 1 (LSD1), PHYTOALEXIN DEFICIENT 4 (PAD4) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) conditionally regulate the cell wall when suppressed in transgenic aspen. During four years of growth in the field the following effects were observed: lignin content was reduced, the cellulose fiber polymerization degree increased and the growth itself was unaffected. The wood of transgenic trees was more efficient as a substrate for saccharification, alcoholic fermentation and bioethanol production. The presented results may trigger the development of novel biotechnologies in the biofuel industry.

Phototherapy is an efficient strategy to respond to oxidative stress and has been in the spotlight in various therapeutic fields through its biological effect, but the exact molecular mechanism has not yet been established. As a result of irradiating RAW264.7 cells with a 630 nm or 850 nm LED with an energy intensity of 0.01J/cm2, cell viability was increased depend on the irradiation time. After H2O2 was added, 630 nm or 850 nm LEDs were irradiated for 10 min or 40 min to increase cell viability by about 1.7- or 1.6-fold, respectively. In addition, 630nm or 850nm LED irradiation showed a significant ROS scavenging effect and significantly reduced TUNEL-positive cells by 45.7% and 37.8%, respectively, compared to cells treated only with H2O2. In the result of flow cytometry, the number of cells in the late apoptosis stage was about 2.3- and 1.8-fold lower than that of the cells treated with H2O2 only, but there was no significance. The Bax/Bcl-2 ratio of cells irradiated with 630 nm or 850 nm LED was significantly lower than that of cells treated with H2O2 only, and the expression of procaspase-3 and cleaved PARP was also significantly expressed in the direction of suppressing cell death. In conclusion, the ROS scavenging activity by 630 nm or 850 nm LED irradiation, leading the expression of cell death pathway proteins in the direction of inhibiting cell death.

Renal cell carcinoma (RCC) is the second most common cancer of the urinary system. The current therapeutic strategies are based on partial or total nephrectomy and/or targeted therapies based on immune checkpoint inhibitors to which patients are often refractory. Preventive and screening strategies are not existing and the few available biomarkers for RCC are characterized by the lack of sensitivity, outlining the need of novel noninvasive and sensitive biomarkers for an early diag-nosis and a better disease monitoring. Blood liquid biopsy (LB) is a non- or minimally invasive procedure for a more representative view of tumor heterogeneity than the tissue biopsy, poten-tially allowing real-time monitoring of cancer evolution. Growing interest is focused on the extra-cellular vesicles (EVs) secreted by either healthy or tumoral cells and recovered in a variety of bio-logical matrices, blood included. EVs are involved in cell-to-cell crosstalk transferring their mRNAs, miRNAs, and proteins content. In particular, transferred miRNAs may regulate the tu-morigenesis and proliferation also impacting on resistance to apoptosis, thus representing poten-tial useful biomarkers. Here we present the latest efforts in the identification of circulating miR-NAs in blood samples, focusing on the potential use of EV derived miRNAs as RCC diagnostic, prognostic markers.