Gossypol is a complex plant polyphenol reported to be cytotoxic and anti-inflammatory, but little was known about its effect on gene expression in macrophages. The objective was to explore gossypol’s toxicity and its effect on gene expression involved in inflammatory responses, glucose transport and insulin signaling pathway in mouse macrophages. Mouse RAW264.7 macrophages were treated with multiple concentrations of gossypol for 2-24 h. Gossypol toxicity was estimated by MTT assay and soluble protein content. qPCR analyzed the expression of anti-inflammatory tristetraprolin family (TTP/ZFP36), proinflammatory cytokine, glucose transporter (GLUT) and insulin signaling genes. Cell viability was greatly reduced by gossypol, accompanied with dra-matic reduction of soluble protein content in the cells. Gossypol treatment resulted in an increase of TTP mRNA level 6-20 fold and increased ZFP36L1, ZFP36L2 and ZFP36L3 mRNA levels by 26-69 fold. Gossypol increased proinflammatory cytokine TNF, COX2, GM-CSF, INFγ and IL12b mRNA levels up to 39-458 fold. Gossypol treatment upregulated mRNA levels of GLUT1, GLUT3 and GLUT4 genes as well as INSR, AKT1, PIK3R1 and LEPR but not APP genes. This study demonstrated that gossypol induced macrophage death and reduced soluble protein content that was accom-panied with massive stimulation of anti-inflammatory TTP family and proinflammatory cytokine gene expression as well as elevation of gene expression involved in glucose transport and insulin signaling pathway in mouse macrophages.

Imidazo[1,2-a]pyridines have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of imidazo[1,2-a]pyridine derivatives by screening its ability as a pro-oxidant. Imidazo[1,2-a]pyridine derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562 and Jurkat leukemia cells. The imidazo[1,2-a]pyridine derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 hours. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress as a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.

The modulation of Nrf2 activity has been reported to be implicated in the pathology of various neurological disorders, including epilepsy. Previous studies have demonstrated that Nrf2 is activated in the post-status epilepticus rat model, however, the spatio-temporal, as well as cell type-specific expression of Nrf2 following brief epileptic seizures remains unclear. Here, we evaluated how an acute epileptic seizure affected the expression of Nrf2 and its downstream genes in the cortex and the hippocampus up to 1-week following the induced seizure. We found that after a pentylenetetrazol-induced seizure, Nrf2 significantly increased at 24 h at the mRNA level and 3 to 6 h at the protein level in the cortex. In the hippocampus, the Nrf2 mRNA level peaked at 3 h after the seizure, and no significant changes were observed in the protein level. Interestingly, the mRNA level of Nrf2 downstream genes peaked at 3-6 h after seizure in both the cortex and the hippocampus. A significant increase in the expression of Nrf2 was observed in the neuronal population of CA1 and CA3 regions of the hippocampus, as well as in the cortex. Moreover, we observed no change in the co-localization of Nrf2 with astrocytes neither in the cortex nor in CA1 and CA3. Our results revealed that following a brief acute epileptic seizure, the expression of Nrf2 and its downstream genes is transiently increased and peaked at early timepoints after seizure predominantly in the hippocampus, and this expression is restricted to the neuronal population.

In this paper, a study of modeling PV cell (solar cell), PV module (solar modules) and PV array solar array) using Matlab/Simulink software is presented. This study is focused on the study to design photovoltaic cell, photovoltaic modules, photovoltaic panels and PV array (solar array) and to analyze the change in PV performance according to changes in different parameters such temperature, solar irradiation, reverse saturation current, series resistance and shunt resistance. This study shows the PV and IV characteristics curve for each model from which MPP (maximum power point) is determined. In this study, different PV and IV characteristic curves are gained for varying temperatures with specified solar irradiation conditions,s and then the MPP is tracked. The highest power output is also compared between the designed PV module and the selected PV module (MX Solar USA MX60-245)

The load cell is an indispensable component of many engineering machinery and industrial automation for measuring and sensing force and torque. This paper describes the design and analysis of the strain gauge load cell, from the conceptional design stage to shape optimization (based on the finite element method (FEM) technique) and calibration, providing ample load capacity with low-cost material (aluminum 6061) and highly accurate force measurement. The amplifier circuit of the half Wheatstone bridge configuration with two strain gauges has been implemented experimentally with an actual load cell prototype. The calibration test was conducted to evaluate the load cell characteristics and derive the governing equation for sensing the unknown load depending on the measured output voltage. The measured sensitivity of the load cell is approximately 15 mV/N and 446.8 µV/V at a maximum applied load of 30 kg. The findings are supported by FEM results and experiments with an acceptable percentage of errors, which revealed an overall error of 6% in the worst situation. Therefore, the proposed load cell meets the design considerations for axial force measurement for the laboratory test bench, which has a light weight of 20 g and a maximum axial force capacity of 300 N with good sensor characteristics.

Hematological and biochemical reference values in sickle cell disease (SCD) are crucial for patient management and evaluation of interventions. This study was conducted at Muhimbili National Hospital (MNH) in Dar es Salaam, to establish laboratory reference ranges in SCD at steady-state. Patients were grouped into five age groups with respects to their sex. Aggregate functions were used to handle repeated measures within the indi-vidual level in each age group. A nonparametric approach was used to smooth the curves and a parametric approach was used to determine SCD normal ranges. Comparison between males and females and against the general population was documented. Data from 4,422 patients collected from 2004-2015 were analyzed. The majority of the patients (35.41%) were children aged between 5-11 years. There were no significant differences (p≥0.05) in mean corpuscular hemoglobin concentration (MCHC), lymphocytes, basophils and bilirubin direct observed between males and females. Significant differences (p<0.05) were observed in all selected parameters across age groups except neutrophils and MCHC in adults, as well as platelets and alkaline phosphatase in infants when SCD estimates were compared to the general population. Laboratory reference ranges in SCD at steady-state were different from those of the general population and varied with sex and age. The established reference ranges for SCD at steady-state will be a helpful in the management and monitoring of the progress of SCD.

UPF3B is a constituent of the classical nonsense-mediated mRNA decay (NMD) pathway that degrades both the aberrant transcripts and a set of physiological transcripts. In higher eukaryotes, UPF3B have significant biochemical functions in diverse cellular processes including NMD and translation. UPF3B plays a crucial role in neuronal development and differentiation. Next-generation sequencing technologies identified several loss-of-function mutations in the UPF3B gene that results in neuro-developmental disorders in humans. To uncover the mechanistic role of UPF3B in neuronal functions, we have generated the UPF3B-knockout mammalian cell line model system using CRISPR-Cas9 gene editing method. RNA-Sequencing Analysis of cellular transcriptome from UPF3B-KO cells identified specific genes involved in cell growth and neuronal functions. Altered expression of genes related to the axon guidance pathway delineated the UPF3B function to regulate the neuron-specific genes. Functional enrichment analysis identified the genes involved in the disorders related to mental health and intellectual disability. Our study has the potential to identify the direct players of intellectual disability and will have broader implications.

More than 800 million tons of fish are utilizing in a year and 25-30% become waste. The waste amount is beneficial source for extraction of collagen. But procedure of extraction is still to be optimized. The current study was designed to extract collagen from fish through fish waste fermentation under various conditions. For collagen extraction we did lactic acid fermentation in which yogurt and Dough bacteria was added with fish sample and placed it in incubator at 30ºC for one month. In yogurt and dough culture have at least 10 type of lactic acid bacterial species. After every week we check PH of each sample and take soup of that sample. After centrifugation of that sample’s TCA (Trichloroacetic acid) precipitation was done of yogurt and dough sample and kept at -20ºC. then did SDS-PAGE) using 6% resolving and 5% stacking gel of already stored sample. Then HaCaT cells (1 × 10⁴ cells/well) were cultured in 96-well flat-bottom culture plates and treated with appropriate doses of FFCP (fermented fish collagen peptide) for 24 and 48 hours.The SDS-PAGE revealed that the collagen protein of fish had doublet pattern for α1 and α2 chains at corresponding to 145 kDa and 132 kDa respectively. The density for α1 twice as compared to α2. Our result agrees that The fish collagen consists mostly of α-chain as well as little amount of inter and intra molecular cross-linked components of α-chains; b (dimmer) and c (trimer). Different biochemical tests were done for identification of lactic acid bacteria catalase positive, citrate positive, urease negative. Our fermented fish collagen and peptides mixture were test for cellular cytotoxicity and proliferative effect on HaCaT cells. Current result shows that fermented extracted collagen are nontoxic and induce the proliferation of HaCaT cells. Current study is supported by various studies that revealed the medical application of fish extracted collagen as underline.

Diffuse large B cell lymphoma (DLBCL), the most frequent type of non-Hodgkin lymphoma in adulthood, remains challenging clinical issues. Despite enhanced remission rates can be achieved, there are one-third of patients who will not respond to current treatment or will relapse with resistant disease, necessitating ongoing efforts on effective treatment strategies and agents. The vacuole H+-ATPase inhibitor bafilomycin A1 is broadly used to block late stage of autophagy flux at high concentration. In this study, we show that, to our surprise, bafilomycin A1 effectively inhibited and killed DLBCL cells at nanomolar concentrations (5nM). Bafilomycin A1 targeted cell cycle regulators cyclin D1 and cyclin E2 to induce cell cycle arrest in G0/G1 phase. Meanwhile, it induced caspase-dependent apoptosis with concomitant cleaved caspase-3 and Parp. Furthermore, we found that bafilomycin A1 inhibited autophagy flux at both early and late stages of the autophagy flux through activating ERK and mammalian target of rapamycin signaling, as well as by inhibiting the degradation of autolysosomes. We speculated that bafilomycin A1 as autophagy inhibitor might enhance the effect of DLBCL chemotherapeutic drug rituximab. Accordingly, our results provided evidence that the combination of bafilomycin A1 with rituximab enhanced the inhibition of DLBCL cells notably. Taken together, our data suggest that bafilomycin A1 may be a promising candidate drug in the therapy of diffuse large B cell lymphoma.

The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is activated by the small G-protein, RHEB-GTPase. On lysosome, RHEB activates mTORC1 by binding the domains of N-heat, M-heat, and FAT, which allosterically regulates ATP binding in the active site for further phosphorylation. The crucial role of RHEB in regulating growth and survival through mTORC1, makes it a targetable site for anti-cancer therapeutics. However, the binding kinetics of RHEB to mTORC1 is still unknown at the molecular level. Therefore, we studied the kinetics by in vitro and in-cell protein-protein interaction (PPI) assays. For this, we used the split-luciferase system (NanoBiT®) for in-cell studies, and prepared proteins for the in vitro measurements. Consequently, it was shown that RHEB binds to the whole mTOR both in the presence or absence of GTPɣS, with five-fold weaker affinity in the presence of GTPɣS. Also, RHEB bound to the truncated mTOR fragments of N-heat domain (60-167) and M-heat domain (967-1023) in a GTP independent manner. Furthermore, RHEB bound to the truncated kinase domain (2148-2300) with higher affinity also in GTP independently. In conclusion, RHEB binds two different binding sites of mTOR, which probably regulates the kinase activity of mTOR through multiple different molecular mechanisms.

Heart regeneration after myocardial infarction remains challenging in reconstruction of blood resupply system. Here, we find that in zebrafish heart after resection of the ventricular apex, the local myocardial cells and the clotted blood cells undergo cell remodeling process via cytoplasmic exocytosis and nuclear reorganization within revascularization-based blastema. The regenerative processes are visualized by spatiotemporal expression of three blastema representative factors (alpha-SMA- which marks for fibrogenesis, Flk1for angiogenesis/hematopoiesis, and Pax3a for remusculogensis)，and two histone modifications (H3K9Ac and H3K9Me3 mark for chromatin remodeling). Using the cultured zebrafish embryonic fibroblasts we identify blastema fraction components and show that Krt5 peptide could link cytoskeleton network and BMP4 signaling pathway to regulate the transcription and chromatin accessibility at the blastema representative genes and bmp4 genes. Our study provides new mechanistic insights into the epithelial-dependent and revascularization-based blastema regeneration for potential myocardial infarction therapy.

Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than parent the cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable material for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal and epithelial type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as non-toxic. Based on these results, fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cells protection against oxidative stress.

T-cell mediated immune responses should be regulated to avoid the development of autoimmune or chronic inflammation diseases. Several mechanisms have been described to regulate this process, namely death of overactivated T cells by cytokine deprivation, suppression by T regulatory cells (Treg), induction of expression of immune checkpoint molecules such as CTLA-4 and PD-1, or activation-induced cell death (AICD). In addition, activated T cells release membrane microvesicles called exosomes during these regulatory processes. In this review, we revise the role of exosome secretion in the different pathways of immune regulation described to date and its importance in the prevention of autoinmune disease. Expression of membrane-bound death ligands on the surface of exosomes during AICD, or the more recently described transfer of miRNA or even DNA inside T-cell exosomes are molecular mechanisms that will be analyzed.

Reversible protonic ceramic cells (rPCCs) combine two different operation regimes, fuel cell and electrolysis cell modes, which allow reversible chemical-to-electrical energy conversion at reduced temperatures with high efficiency and performance. Here we present novel technological and materials science approaches, enabling a rPCC with symmetrical functional electrodes to be prepared using a single sintering step. The response of the cell fabricated on the basis of P–N–BCZD|BCZD|PBN–BCZD (where BCZD = BaCe_0.5Zr_0.3Dy_0.2O_3–δ, PBN = Pr_1.9Ba_0.1NiO_4+δ, P = Pr₂O₃, N = Ni) is studied at different temperatures and water vapor partial pressures (pH₂O) by means of volt-ampere measurements, electrochemical impedance spectroscopy and distribution of relaxation times analyses. The obtained results demonstrate that symmetrical electrodes exhibit classical mixed-ionic/electronic conducting behavior with no hydration capability at 750 °C; therefore, increasing the pH₂O values in both reducing and oxidizing atmospheres leads to some deterioration of their electrochemical activity. At the same time, the electrolytic properties of the BCZD membrane are improved, positively affecting the rPCC’s efficiency. The electrolysis cell mode of the rPCC is found to be more appropriate than the fuel cell mode under highly humidified atmospheres, since its improved performance is determined by the ohmic resistance, which decreases with pH₂O increasing.

In this paper, an analytical investigation of the combined effect of through flow and magnetic field on the convective instability in an electrically conducting fluid layer, bounded in a Hele-Shaw cell is presented within the context of linear stability theory. The Galarkin method is utilized to solve the eigenvalue problem. The outcome of the important parameters on the stability of the system is examined analytically as well as graphically. It is observed that the through flow and magnetic field have both stabilizing effects, while the Hele-Shaw number has destabilizing effect on the stability of system. It is also found that the oscillatory mode of convection possible only when the magnetic Prandtl number takes the values less than unity.

Background. Polytetrafluoroethylene (PTFE) patch is commonly used during surgical closure for atrial septal defect (ASD) and/or ventricular septal defect (VSD). It has several limitations such as inability to grow, repair, and remodel. Aneurysm formation, thrombosis, and the inability of patches to grow or remodel are usual, especially in children and young adults. To tackle these limitations, we try to use fibronectin and human adipose-derived mesenchymal stem cells (hAMSCs) in PTFE patch. Objective. To understanding positive impact of fibronectin to enhance hAMSCs cell-to-cell adherence and cell-to-patch surface attachment into PTFE patch for future ASD or VSD closure. Methods. Cultured of hAMSCs cells were fixated with 15 mL methanol and CD90+, CD105+, CD45- antibodies were labeled FITC, rinsed with PBS and analyzed under fluorescence microscope for 15 minutes. Fibronectin solution 0.1% were used to soak patch scaffolds for approximately 2 hours duration, and then dried for 20 minutes for treatment group. As for control group, Fibronectin solution was not added on the culture. The samples were examined with scanning electron microscope (SEM). Results. SEM examination showed incomplete attachment of the cells even after 10 days on control group at 1.14 ±1.13 (Figure 2). In contrast, treatment group showed more cells attached to the patch surface at 31.25 ±13.28 (p 0.000) (Figure 3). Observation at 5 days was 17.67 ± 20.21, at 7 days was 12.11 ± 10.94, at 10 days was 18.83 ± 23.25. No significant statistical difference of mean cell per view among each treatment group (p 0.802). Conclusion. Fibronectin has a positive impact on hAMSCs attachment seeded onto PTFE patch. These properties, in combination with their developmental plasticity, have generated tremendous interest because of the potential use of hAMSCs in regenerative medicine to replace damaged tissues.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

Abstract: Background: Irreversible electroporation (IRE) is a form of non-thermal ablation that delivers pulses of high voltage electrical current between electrodes. The role of IRE in the treatment of colorectal hepatic metastases is unestablished. This study is an international ques-tionnaire survey of the use of IRE for colorectal hepatic metastases. Methods: A questionnaire addressing views on the use of IRE for colorectal liver metastases was circulated to clinicians with an interest and/or expertise in this technique. Results: 64 clinicians from 17 different countries replied to the questionnaire. Thirty-six (56%) had experience of treating patients with colorectal liver metastases with IRE. The preferred mode of delivery of IRE was percutaneous treatment under CT guidance. Thirty-three (70% respondents) used IRE exclusively for lesions in proximity to inflow or outflow structures. Twenty (43% respondents) used IRE as their sole ablative treat-ment whilst 19 (40% respondents) used IRE in combination with thermal ablation. The maximum number of lesions that could be treated by IRE was two and preferred size of lesion was

This review article provides useful information on TiO2 and ZnO photocatalysts and their derivatives in removing organic contaminants such as different types of dyes, hydrocarbons, pesticides, etc. Also, the reaction mechanism of TiO2 and ZnO photocatalysts and their derivatives was investigated. In addition, the impact of adding metallic (e.g., Ag, Co, Pt, Pd, Cu, Au, Ni) and non-metallic (e.g., C, N, O, S) dopants to their structure on the photodegradation efficiency of organic compounds was thoroughly studied. Moreover, advantages and disadvantages of various synthesis procedures of ZnO and TiO2 nanocatalysts were discussed and compared. Furthermore, the impact of photocatalyst dosage, photocatalyst structure, contaminant concentration, pH, light intensity and wavelength, temperature and reaction time on the photodegradation efficiency was studied. According to previous studies, adding metallic and non-metallic dopants to the TiO2 and ZnO structure led to a remarkable enhance in their stability and reusability. Besides, doped TiO2 and ZnO demonstrated remarkable photocatalytic efficiencies in eliminating various types of organic contaminants.

The study presents empirical results investigating the relationships among renewable and non-renewable energy consumption, CO2 emissions, and GDP within the Visegrád Group (V4) countries. Using FMOLS/DOLS and ARDL approaches, along with causality tests based on the Toda-Yamamoto method, the study explores these relationships at a regional level. The findings indicate that renewable energy has a small positive impact on long-term economic growth, with non-renewable energy having a more significant effect. Moreover, CO2 emissions have a negative impact on economic growth, suggesting ongoing reliance on non-renewable energy sources and a burden on economic expansion. On an individual country level, the effects vary. Poland, Slovakia, and Hungary exhibit a negative relationship between CO2 emissions and economic growth. Energy sources also differ in impact: in Poland, the Czech Republic, and Slovakia, non-renewable energy significantly affects economic growth, while in Hungary, renewable energy plays a more substantial role. Causality tests reveal a causal relationship between CO2 emissions and economic growth in the Czech Republic and Poland, suggesting CO2 emissions significantly influence economic expansion. In terms of energy production, renewable energy is causally related to economic growth in the Czech Republic and Slovakia. All countries demonstrate significant causality between non-renewable energy and economic growth. Additionally, a relationship between renewable energy and CO2 emissions is confirmed in Poland.

Abstract Psychiatric care in Spain has experienced relevant changes both in the legislative and conceptual frameworks. This new approach advocates for the combination of carrying out mental health promotion, prevention of alterations and early diagnosis and treatment, enhancing actions against stigma and emphasising the attention on the most vulnerable groups, like childhood and youth. For that, it has seen fit to perform a nursing intervention on Education and Promotion of mental health for teachers and counsellors of a secondary school located in Valencia, with the general objective of assessing their impact on stigma. Non-randomised clinical trial in which a nursing intervention on Education and Promotion of mental health was performed. Pre-intervention tools: multiple choice test validated by a group of experts; pre and post-intervention: AQ-27 (stigma attribution); in order to check its acceptance, satisfaction surveys were used. The inferential analysis included the Wilcoxon Test (pre and post AQ-27) and the Pearson Correlation Test for the quantitative variables of interest. Sample (n=22): women aged 47.96 ± 10.12 years with 18.64 ± 10.34 years of work experience. The predominant stigmatising attitude before and after intervention was “Coercion”. The ones with lower score were “Segregation” and “Anger”. The p-values obtained in the Wilcoxon Test were statistically significant (p-value <0.05) except for “pre and post Responsibility” and “pre and post Pity”. The following constructs of interest were faced: “Age” vs “Fear” (r= -0.48, moderate), “Professional experience” and “Fear” (r= -0.46, moderate) and “Help” and “Psychosis test” (r= 0.51, severe). The overall satisfaction score was 9/10. Despite the scores obtained in “Coercion” and “Psychosis”, the intervention was useful for reducing stigma in the sample.

This paper aims to explore differences in personality traits, focusing on the levels of primary psychopathy, between formal leaders of family and non-family companies as well as assessing differences in the job satisfaction levels of their employees. Moreover, we assess the relationship between the employees' perception of their formal leader’s primary psychopathy levels and their job satisfaction levels in family firms. The empirical evidence is provided by a sample of 95 Portuguese employees, who responded to a questionnaire that included their perception of their formal leader’s primary psychopathy level and job satisfaction measures. All respondents work in small and medium-sized private companies with no management responsibilities and under formal hieratical supervision. The initial idea that family firms’ employees perceive lower levels of primary psychopathy in their formal leaders than non-family firms’ employees was confirmed. However, employees of family and non-family firms did not differ in their job satisfaction levels. The results also support the notion that perceived levels of primary psychopathy in formal leaders are negatively associated with the employees’ job satisfaction levels. These findings contribute to the research literature by addressing two aspects under-addressed in the comparison between family and non-family firms, while offering insights on the relationship between primary psychopathy in formal leaders and job satisfaction levels of employees working in family firms.

Rapid progress in gene editing based on clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) has revolutionized the study of gene and genome function and genetic disease correction. While numerous genetically modified cellular and animal models have been created to understand biological processes, the clinical application of CRISPR/Cas tools has been impeded by off-targeting and delivery problems. It is generally accepted that the delivery of CRISPR in the form of a ribonucleoprotein complex (RNP) substantially reduces the time of DNA exposure to the effector nuclease, minimizing off-target effects and facilitating clinical usage. This review focuses on CRISPR/Cas RNP delivery with retro/lentiviral particles and exosomes, whose parallel production by cells transfected with viral vectors is underestimated. We critically evaluate specific mechanisms of extracellular particle formation and loading with CRISPR/Cas for each system. Additionally, the details of Cas-nanoparticle entry and uncoating, previously unappreciated in the context of gene editing efficiency, are discussed. Based on existing knowledge about the consequences of intervention in retroviral assembly, entry, or exosome formation, we outline the potential problems with CRISPR/Cas delivery using extracellular nanoparticles and ways to address them.

Wire-driven hyper-redundant continuum manipulators are gaining more popularity and finding more applications in industry and in minimally invasive surgery. Unlike traditional rigid link manipulators, continuum robots with a flexible backbone structure are able to work in a highly constrained workspace and in an unstructured environment. However, in spite of a possible wide range of reachability, continuum manipulators have some issues related to payload capacity, accuracy and control. Therefore, in this research, we propose a novel hyper-redundant continuum robot with a passive sliding disc mechanism to improve payload capacity and accuracy. To prove the sliding mechanism concept, we demonstrate a comparison analysis with a conventional non-sliding continuum robot arm in a payload test, a bending test and a reachability test. Moreover, with this novel design, we are proposing robot kinematics and kinetic formulation and simulation results to validate the effectiveness of the sliding disc mechanism.

The World Health Organization (WHO) cancer agency predicts that more than 35 mil-lion cases of will be experienced in 2050, a 77 % increase over the 2022 estimate. Cur-rently, the leading cancer diagnosed cancer are breast, lung and colorectal. There is no standardized tool for cancer diagnosis; initially clinical procedures are guided by the patient´s symptoms and generally involve biochemical blood tests, imaging and biopsy. Label-free nonlinear optical approaches are promising tool for tumor imaging, due to their inherent non-invasive biosafe contrast mechanisms and the ability to monitor collagen-related disorders and metabolic changes during cancer progression. Last ad-vances in nonlinear modalities for tumor imaging are reviewed here. In addition, an application of a blind deconvolution procedure to improve the quality of two-photon images of breast tumor tissues is shown.

In this paper, we explore the hypothesis that topological defects formed in the quark-gluon plasma (QGP) of the early universe, specifically flux tubes and domain walls, could serve as stable dark matter candidates. Theoretical analysis of the QCD vacuum structure reveals that these defects can form due to nontrivial topological configurations, with the Lagrangian density incorporating topological terms. We model the formation and stability of flux tubes and domain walls, estimating their energy densities and dynamics within the QGP. Flux tubes, with energy per unit length approximately given by $\mu \approx \frac{\sigma}{g_s^2}$, and domain walls, characterized by a surface energy density $\sigma_{\text{DW}} \sim \Lambda_{\text{QCD}}^3$, exhibit unique gravitational signatures. These signatures include distinct gravitational lensing patterns due to their linear and planar mass distributions, making them detectable through astrophysical surveys. Furthermore, their minimal interaction with conventional matter aligns well with observational constraints on dark matter properties. We discuss potential experimental approaches for detecting these defects, including high-energy collider experiments and detailed analysis of gravitational lensing data. Our findings suggest that topological defects in the QGP provide a compelling and novel solution to the dark matter problem, offering a new direction for both theoretical investigation and experimental verification.

Accurate calculation of non-covalent interaction energies in nucleotides is crucial for understanding the driving forces governing nucleic acid structures and functions, as well as developing advanced molecular mechanics forcefields or machine learning potentials tailored to nucleic acids. Here, we dissect the nucleotides’ structure into three main constituents: nucleobases (A, G, C, T, and U), sugar moieties (ribose and deoxyribose), and phosphate group. The interactions among these fragments and between fragment and water were analyzed. Different quantum mechanical methods were compared for their accuracy in captuing the interaction energy. The non-covalent interaction energy was decomposed into electrostatics, exchange-repulsion, dispersion, and induction using two ab-initio methods: Symmetry-Adapted Perturbation Theory (SAPT) and Absolutely Localized Molecular Orbitals (ALMO). These caculations provide the benchmark for different QM methods while providing valuable understanding of the roles of various interamolecular forces in hydrogen bonding and aromatic stacking.

We overview the main equations of the Rayleigh-Ritz variational method and discuss their connection with the problem of simultaneous diagonalization of two Hermitian matrices.

Recommendation systems are crucial in navigating the vast digital market. However, user data’s dynamic and non-stationary nature often hinders their efficacy. Traditional models struggle to adapt to the evolving preferences and behaviours inherent in user interaction data, posing a significant challenge for accurate prediction and personalisation. Addressing this, we propose a novel theoretical framework, the Non-stationary Transformer, designed to capture and leverage the temporal dynamics within data effectively. This approach enhances the traditional transformer architecture by introducing mechanisms accounting for non-stationary elements, offering a robust and adaptable solution for recommendation systems. Our experimental analysis, encompassing deep learning and reinforcement learning paradigms, demonstrates the framework’s superiority over benchmark models. The empirical results confirm the efficacy of our proposed framework, which not only provides significant performance enhancements, approximately 8% in Logloss reduction and up to 2% increase in F1 score but also underscores its potential applicability across accumulative reward scenarios. These findings advocate adopting Non-stationary Transformer models to tackle the complexities of today’s recommendation tasks.

This study aimed to investigate whether non-fasting plasma triglycerides were associated with diabetes mortality. It included 7,312 US adult participants. Diabetes mortality data were obtained via linkage to the National Death Index (NDI) records. Hazard ratios of non-fasting plasma triglycerides for diabetes mortality were assessed using Cox proportional hazards models, adjusting for age, gender, ethnicity, obesity, poverty-income ratio, education levels, physical activity, alcohol consumption, cigarette smoking status, survey period, hypercholesterolemia, hypertension, diabetes, and family history of diabetes. Among these participants, 1,180 had diabetes. A total of 420 diabetes-caused deaths were recorded during a mean follow-up of 16.8 years. A 1-natural-log-unit increase in non-fasting plasma triglycerides was associated with a 41% higher diabetes mortality risk (hazard ratio, 1.41; 95% confidence interval, 1.19-1.67). Participants with non-fasting plasma triglycerides in the highest quintile, versus those in the lowest quintile, had a 144% higher diabetes mortality risk (hazard ratio, 2.44; 95% confidence interval, 1.49-4.02). The positive association of non-fasting plasma triglycerides with diabetes mortality was independent of diabetes status at the baseline. In conclusion, this study demonstrated that non-fasting plasma triglycerides were positively associated with diabetes mortality, independent of diabetes status at the baseline. Non-fasting triglycerides may be a therapeutic target for diabetes-related complications.

. Gut microbiome reflects healthy and predicts possible disease in hosts. A holistic view of this community is needed, focused on identification species, and on the dissection of how species interact with their host and with each other, regardless of whether their presence is beneficial, inconsequential, or detrimental. Distribution of gut-associated eukaryotes within and across NHPs is likely driven by host behavior and ecology. To ascertain the existence of free-living amoebae (FLA) in the gut of wild and captive non-human primates (NHPs), 01 sample stools were collected and submitted to culture-dependent and microscopy examination and DNA sequencing. FLAs were detected in 45.4% (46/101) of fecal samples analysed and their morphological characteristics matching those of Acanthamoeba spp, Vermamoeba spp, and fan-shaped amoebae of the family Vannellidae. Sequence analysis of the PCR- products revealed that the suspected amoebae are highly homologous (99% identity and 100% query coverage) with Acanthamoeba genotype T4 and Vermamoeba vermiformis amoebae. The results showed a great diversity of FLAs in the NHP microbiome, which may pose a potential risk to the health of NHPs. To the best of our knowledge, this is the first report the presence of FLAs in NHPs naturally infected. However, it is not known whether gut-borne FLA are exploiting a viable ecological niche, or whether they are simply transient residents in the gut.

Spinal cord injuries (SCI) can result in sensory and motor dysfunctions, which were long-considered permanent. Recent advancement in electrical neuromodulation has been proven to restore sensorimotor function in people with SCI. These stimulation protocols, however, were mostly invasive, expensive, and difficult to implement. In this study, transcutaneous electrical stimulation (tES) was used to restore over-ground walking of an individual with 21 years of chronic paralysis from a cervical SCI. After a total of 66 weeks of rehabilitation training with tES, which included standing, functional reaching, reclined sit-up, treadmill walking and active biking, significant improvement in lower-limb volitional movements and overall light touch sensation were shown by International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score. By the end of the study, the participant could walk in a 4-meter walking test with the aid of a walking frame and ankle foot orthoses. The success in the sensorimotor recovery of our study participant sheds light on the future of non-invasive neuromodulation treatment for SCI paralysis.

The mites that infest laying hens and broiler chickens in poultry farms have caused great inconvenience to the industry due to the difficulty of controlling or eliminating their populations within the production systems. Dermanyssus gallinae and Ornithonyssus spp. are the mites that mainly interfere with the well-being of the poultry, harming the animals’ health and damaging the production and quality of the end product, with special emphasis on Ornithonyssus sylviarum and Ornithonyssus bursa. The objective of this article is to analyze the impact of hematophagous mites that infest commercial egg and meat production systems, the consequences of this form of parasitism, and discuss the methods of control it, including chemical and non-chemical means with the use of plants, entomopathogenic fungi, diatomaceious earth-based products and synthetic silica, and new lines of study aimed at developing vaccines as a new way of effectively controlling these pests.

Long non-coding RNAs (LncRNAs) are mRNA-like molecules that do not encode for proteins and that are longer than 200 nucleotides. LncRNAs play important biological roles in normal cell physiology and organism development. Therefore, deregulation of their activities is involved in disease processes such as cancer. Lung cancer is the leading cause of cancer-related deaths due to late stage at diagnosis, distant metastasis, and high rates of therapeutic failure. LncRNAs are emerging as important molecules in lung cancer for their oncogenic or tumor suppressive functions. LncRNAs are highly stable in circulation, presenting an opportunity for use as non-invasive and early-stage cancer diagnostic tools. Here, we summarize latest works providing in vivo evidence available for LncRNAs role in cancer development, therapy-induced resistance, and their potential as biomarkers for diagnosis and prognosis, with a focus on lung cancer. Additionally, we discuss current therapeutic approaches to target LncRNAs. The evidence discussed here strongly suggests that investigation of LncRNAs in lung cancer in addition to protein-coding genes will provide a holistic view of molecular mechanisms of cancer initiation, development, and progression, and could open a new avenue for cancer treatment.

In the paper we suggest an implementation of the non-commutative logic and apply its operators for decision-making in the group of autonomous agents. The suggested operators extend the uninorm and absorbing norm aggregators and use an additional asymmetry parameter that defines the “level of non-commutativity”. The value of this parameter is specified using the perception bias of humans measured in the experiments. The suggested operators and decision-making method are illustrated by simulated behavior of mobile robots in the group.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the disease COVID-19 has wreaked havoc on the health and economy of humanity. In addition, the disease is observed in domestic and wild animals. The disease has impacted directly and indirectly every corner of the planet. Currently, there are no vaccines and effective therapies for COVID-19. SARS-CoV-2 is an enveloped virus with a single-stranded RNA genome of 29.8 kb. More than two-thirds of the genome comprises Orf1ab encoding 16 non-structural proteins (nsps) followed by mRNAs encoding structural proteins, spike (S), envelop (E), membrane (M), and nucleocapsid (N). These genes are interspaced with several accessory genes (open reading frames [Orf] 3a, 3b, 6, 7a, 7b, 8, 9b, 9c and 10). The functions of these proteins are of particular interest for understanding the pathogenesis of SARS-CoV-2. Several of the nsps (nsp3, nsp4, nsp6) and Orf3a are transmembrane proteins involved in regulating the host immunity, modifying host cell organelles for viral replication and escape and hence considered drug targets. In this paper we report mapping the transmembrane structure of the non-structural proteins of SARS-CoV-2.

Non-vertebrate species represent about ~95% of known metazoan (animal) diversity. They remain to this day relatively unexplored genetically, but understanding their genome structure and function is pivotal for expanding our current knowledge of evolution, ecology and biodiversity. Following the continuous improvements and decreasing costs of sequencing technologies, many genome assembly tools have been released, leading to a significant amount of genome projects being completed in recent years. In this review, we examine the current state of genome projects of non-vertebrate animal species. We present an overview of available sequencing technologies, assembly approaches, as well as pre and post-processing steps, genome assembly evaluation methods, and their application to non-vertebrate animal genomes.

As Solar Photovoltaics in buildings reaches maturity, grid integration and economic yield are topics of greater interest. The traditional design of photovoltaic installations has considered the optimal orientation of photovoltaic modules to be that which yields the maximum annual energy production. The influence of the consumption patterns and the hourly-variable electricity prices implies that this traditional optimal design might not be the most profitable. Using a full-year dataset for a residential installation, alternative installations using canopies and modules attached to the façades are simulated. Simulating the energy balances for different annual consumptions, it is found that the canopy and façade installations offer better self-consumption of the PV produced energy, reflected in a 9% higher self-consumption degree using modules on façades and a 5% using canopies. The economic evaluation under the new electricity tariffs in Spain shows a better profit for PV self-consumption, reducing by more than 2 years the time of return on investment. The analysis of different alternatives for an industrial PV has allowed us to identify several benefits for these orientations, such as an increase in annual energy production of up to 59% over the optimal-producing orientation, that are confirmed after several months of operation.

The current paper is devoted to the introduction of simpler Eulerian variational principles from which all the relevant equations of non-barotropic stationary magnetohydrodynamics can be derived for magnetic fields which lie on surfaces. A variational principle is given in terms of three independent variables for stationary non-barotropic magnetohydrodynamic flows. This is a smaller number of variables than the eight variables which appear in the standard equations of non-barotropic magnetohydrodynamics which are the magnetic field, the velocity field, the specific entropy and the density. We further investigate the case in which the flow along magnetic lines is not ideal.

Although cancers account for over 16% of all global deaths annually, at present, no reliable therapies exist for most types of the disease. As protein folding facilitators, heat shock proteins (Hsps) play an important role in cancer development. Not surprisingly, Hsps are among leading anticancer drug targets. Generally, Hsp70s are divided into two main subtypes: canonical Hsp70 (E. coli Hsp70/DnaK homologues) and the non-canonical (Hsp110 and Grp170) members. These two main Hsp70 groups are delineated from each other by distinct structural and functional specifications. Non-canonical Hsp70s are considered as holdase chaperones, while canonical Hsp70s are refoldases. This distinct characteristic feature is mirrored by the distinct structural features of these two groups of chaperones. Hsp110/Grp170 members are larger as they possess an extended acidic insertion in their substrate binding domains. While the role of canonical Hsp70s in cancer has received a fair share of attention, the roles of non-canonical Hsp70s in cancer development has received less attention in comparison. In the current review, we discuss the structure-function features of non-canonical Hsp70s members and how these features impact on their role in cancer development. We further mapped out their interactome and discussed the prospects of targeting these proteins in cancer therapy.

The development and optimization of an effective non-viral gene delivery method for genetic manipulation of primary human T cells is a major challenge in clinical immunotherapy researches. According to the low transfection efficiency of conventional methods in human primary T cells, there is an effort in order to increase the transfection rate in these cells. Protamine is an FDA-approved compound with a documented safety profile that enhances DNA condensation for gene delivery. In this study, the effect of protamine on the transfection efficiency of standard transfection reagents, TurboFect, and Lipofectamine 2000 was evaluated in order to transfect primary human T cells. Results demonstrated that protamine condenses DNA and increases the positive charge of DNA/Cargo complex efficiently without any cytotoxic effect on the primary human T cells. The results also revealed that the DNA/Protamine/Cargo complexes effectively transfect human primary T cells.

The quality and shelf-life of NCS (Non-centrifugal sugar) mainly depend on the moisture content present in it. NCS formed by the current practice of open sun drying contains moisture substantially greater than the acceptable level of 3%. This paper presents the work taken up to design a tunnel dryer to attain require moisture content in granular NCS for various load conditions. Initially, an experimental investigation had been carried out on a laboratory scale dryer to achieve required moisture content (< 3%) for various load conditions. This experimental data was used for validating two drying models and found that one of the models is best suitable for designing an industrial-scale dryer. For various load conditions on each tray and dryer exit temperature, nine different cases were arrived at. The number of trucks, trays, drying time and energy requirements were computed using the suitable theoretical model. Tunnel dryer with a length of 18 m, a height of 1.2 m, a width of 1 m, number of trucks of 18 and 24 number of trays on each truck was found to be the suitable dryer to dry 1 tone of NCS based on the minimum energy requirement of 176.49 MJ, and a minimum drying time of 68 minutes.

Non-enzymatic glucose sensing is a crucial field of study because of the current market demand. This study proposes a novel design of glucose sensor with enhanced selectivity and sensitivity by using graphene Schottky diodes, which is composed of Graphene/Platinum Oxide/n-Silicon heterostructure. The sensor was tested with different glucose concentrations and interfering solutions to investigate its sensitivity and selectivity. Different structures of the device were studied by adjusting the platinum oxide film thickness to investigate its catalytic activity. It was found that the film thickness plays a significant role in the efficiency of glucose oxidation and hence in overall device sensitivity. Moreover, theoretical investigations were conducted using Density Function Theory (DFT) to better understand the detection method and the origins of selectivity. The working principle of the sensors puts it in a competitive position with other non-enzymatic glucose sensors. DFT calculations provided a qualitative explanation of the charges distributed across the graphene sheet within a system of a platinum substrate with D-glucose molecules above. The proposed graphene/PtO/n-Si heterostructure has proven to satisfy these factors, which opens the door for further developments of more reliable non-enzymatic glucometers for continuous glucose monitoring systems.

Complex blade responses such as a rotating stall or simultaneous resonances are common in modern engines and their observation can be a challenge even for state-of-the-art tip-timing systems and trained operators. This paper analyses forced vibrations of axial compressor blades, measured during the bench tests of the SO-3 turbojet. In relation to earlier studies conducted in ITWL with a small number of sensors, a multichannel tip-timing system let us observe simultaneous responses or higher-order modes. To find possible symptoms of a failure, blade responses in a healthy and unhealthy engine configuration with an inlet blocker were studied. The used analysis methods covered all-blade spectrum and the circumferential fitting of blade deflections to the harmonic oscillator model. The proposed modal solver can track the vibration frequency and adjust the engine order on the fly. That way, synchronous and asynchronous vibrations are observed and analysed together with an extended variant of least squares. The proposed approach helps to avoid common mistakes and saves a lot of work related to configuring the conventional solver.

In this paper, we study a three step iterative scheme to approximate fixed points of Suzuki's generalized non-expansive mappings. We establish some weak and strong convergence results for such mappings in uniformly convex Banach spaces. Further, we show numerically that iterative scheme (1.8) converges faster than some other known iterations for Suzuki's generalized non-expansive mappings. To support our claim, we give an illustrative example and approximate fixed points of such mappings using Matlab program. Our results are new and generalize several relevant results in the literature.

Corporate Diagnosis is now recognized as an important tool by decision makers to predict and correct burgeoning problems that a corporation may face. Methods based on this model stem from the use of mathematics and are increasingly being applied in the analysis of production processes. The goal of this paper is to use a logistic regression to design a scoring model for non-financial corporations in industry. Based on the data obtained from the Registry of the Slovak Republic for 738 non-financial corporations, according to SK NACE 26, SK NACE 27, the proportional financial metrics, using the logistic regression method, were calculated. By applying these methods, two logistic regression models were found to reliably estimate the probability of bankruptcy for a firm.

The nonlocality of entangled quantum mechanical systems is incompatible with the standard interpretation of special relativity as a single 4D Minkowskian metric spacetime. The difficulty is that the definition of a spacetime interval between any pair of events precludes any form of nonlocal interaction, even the relatively benign non-signaling correlations. By an application of the relativity principle, and the use of the space ←→ time symmetry of the Lorentz boost I propose here a reinterpretation of special relativistic spacetime. This new ontology consists of a set of coexisting 3+1D spaces (‘framespaces’), each containing unique content in the form of a complex density. These spaces are related by the Lorentz boost, and coupled pairwise in a manner dictated by the Lorentz transformation. The inter-space coupling acting on the spacetime content gives rise to a nonlocal wave phenomenon, which is identified as quantum wave mechanics. The interspace coupling strength is then inversely proportional to Planck’s constant. The coexistence of multiple spaces is interpreted as momentum superposition, implying that momentum is the fundamental physical basis of quantum superposition. This new spacetime interpretation of quantum mechanics has many consequences, including explanations of quantum non-locality, the spacetime role of Planck’s constant, quantum measurement as a symmetry-breaking process and the redundancy of description of gauge theory.

Computers and artificial intelligence affect every field of life nowadays. In medical image interpretation automatic decision making using algorithms are used increasingly in every sub-field and computer aided diagnosis (CAD) is one of the main tools available to medical science today. CAD systems are used as an augmented option for both the medical practitioner and the patients, with image analysis and interpretation being of primary importance. In particular, spatial relations are used in knowledge representation, and these relations can be used for effective medical image interpretation. In this paper, we put forth an algorithm for defining non-small cells lungs cancer (NSCLC) stages in lungs images interpretation using topological spatial relations. We show an application case study in event motion predictions for lung cancer staging scoring - tumor, nodes and metastasis (TNM) - with combined topological and directional relations.

Recent findings show that preferences for food items can be modified without external-reinforcements using the cue-approach task. In the task, the mere association of food item images with a neutral auditory cue and a speeded button press, resulted in enhanced preferences for the associated stimuli. Here, in a series of 10 independent samples with a total of 255 participants, we show we can enhance preferences using this non-reinforced method for faces, fractals and affective images as well as snack foods, using auditory, visual and even aversive cues. This change was highly durable in follow-up sessions performed one to six months after training. Preferences were successfully enhanced for all conditions, except for negative valence items. These findings promote our understanding of non-reinforced change, suggest a boundary condition for the effect and lay the foundation for development of novel applications.

Today, the style of light construction materials used in building is one of the most important factors in reducing building's dead load and better performance of the structures in the earthquake. One of the ways to reduce the structure weight is to use lightweight blocks instead of using traditional materials. The main purpose of this research is to compare density, compressive strength and water absorption volume of non-load-bearing lightweight blocks made of natural and artificial lightweight aggregates. Scoria lightweight aggregates of Sanandaj, Ghorveh mine, pumice in Tabriz, Bostanabad mine, and Leca in Leca enterprise have been used to make the samples. Given the importance of the materials used, grading of coarse-grained materials has been conducted based on the standard of 7657 and grading of fine materials have been conducted based on the standard of 302.The experiments' results show that Scoria blocks due to hard texture, and high mechanical resistance of their lightweight aggregates, have had higher compressive strength, and density and lower water absorption volume compared to pumice and Lika lightweight aggregate blocks. Pumice blocks despite having desirable compressive strength and lower density compared to the two other blocks have higher water absorption volume, and do not meet the standard conditions. This same factor causes it faces with less interest. Among these Lika blocks with density of 1151.94 (kg per cubic meter) below 2000 kilograms per cubic meter of Iran density standard of 7782 (28-day compressive strength of 2.57 MPa), higher than 2.5 MPa of Iran compressive strength standard of 7782 (and water absorption volume of 282.92 kg per cubic meter) below 288 kilograms per cubic meter of Iran water absorption volume standard of 7782 (as a non-load-bearing lightweight block) have been diagnosed desirable.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

The Um Ara granites are a suite of granitoid rocks located in the south Eastern Desert of Egypt. The combination of Back Scattered Electron imaging (BSE), X-ray compositional mapping, and the data of the Electron Probe Micro Analyzer (EPMA) has provided valuable insights into the alteration process of zircon in the Um Ara granite. The investigated zircon grains have measurable amount of non-formula elements such as U, Th, Hf, REEs, P, Al, Ca, Fe, and Ti, along with extensive structural features indicative of radiation damage. These characteristics point to significant hydrothermal alteration of the zircon following its initial crystallization. The textural and geochemical evidence suggests the alteration of the Um Ara zircons was driven by coupled dissolution-reprecipitation processes influenced by aqueous fluids. The breakdown of accessory minerals like xenotime, thorite, monazite, and apatite during a major hydrothermal event around 1.8 Ga released the non-formula elements (U, Th, P, Ca, Al, Fe, REEs) that were then incorporated into the zircon structures. Subsequent pluvial periods around 50,000-159,000 years ago may have allowed further uptake of these elements during low-temperature alteration. The shear zones within the Um Ara granites facilitated the mobilization and transport of the non-formula element-bearing fluids, likely as carbonate and fluoride complexes. The temperature regime, with fluids remaining below 300°C, was crucial in preserving the radiation damage features in the zircons despite the extensive chemical changes.

The vast majority of antibodies generated against a virus will be non-neutralising1. However, this does not denote an absence of protective capacity. Yet, within the field there is typically a large focus on antibodies capable of directly blocking infection (neutralising antibodies, nAbs) of either specific viral strains or multiple viral strains (broadly-neutralising antibodies, bnAbs). More recently, a focus on non-neutralising antibodies (nnAbs), or neutralisation-independent effects of nAbs, has emerged. These can have additive effects on protection or in some cases, be a major correlate of protection. As their name suggests, nnAbs do not directly neutralise infection but instead, through their Fc domains, may mediate interaction with other immune effectors to induce clearance of viral particles or virally infected cells. nnAbs may also interrupt viral replication within infected cells. Developing technologies of antibody modification and functionalisation may lead to innovative biologics that harness the activities of nnAbs for antiviral prophylaxis and therapeutics. In this review, we discuss specific examples of nnAb actions in viral infections where they have known importance. We also discuss the potential detrimental effects of such responses. Finally, we explore new technologies for nnAb functionalisation to increase efficacy or introduce favourable characteristics for their therapeutic applications.

The response of building elements during earthquakes has been an area of concern for different researchers around the world. The NSEs are the first elements to attain failure, the buildings after damages in safety priority are classified as in “Life Safety” mode, but in reality, they are in “Collapse Safety” mode and the occupants inside the buildings are in a state of “Non-Life Safety” as a result of falling of the hazardous NSE’s like cladding's, partitions, hanging objects. In addition to the Life Cycle Cost Assessment (LCCA), the Social Life Cycle Assessment (SLCA) is overlooked by the majority of the researchers, the community must be prepared to respond to an event more efficiently without any major casualties or loss of life. It is expected that by the end of 2050, almost double the construction will take place, the embodied energy during the pre-construction, post-construction and demolition generates a lot of CO2s into the environment, hence sustainability should be given due importance, helping in the achievement of Sustainable Developmental Goals (SDGs).

We present an any-to-one voice conversion (VC) system, using an autoregressive model and LPCNet vocoder, aimed to enhance the converted speech in terms of naturalness, intelligibility, and speaker similarity. As the name implies, non-parallel any-to-one voice conversion does not require paired source and target speeches and can be employed for arbitrary speech conversion tasks. Recent advancements in neural-based vocoders, such as WaveNet, have improved the efficiency of speech synthesis. However, in practice, we find that the trajectory of some generated waveforms is not consistently smooth, leading to occasional voice errors. To address this issue, we propose to use an autoregressive (AR) conversion model along with the high-fidelity LPCNet vocoder. This combination not only solves the problems of waveform fluidity but also produces more natural and clear speech, with the added capability of real-time speech generation. To precisely represent the linguistic content of a given utterance, we use speaker-independent PPG features (SI-PPG) computed from an automatic speech recognition (ASR) model trained on a multi-speaker corpus. Next, a conversion model maps the SI-PPG to the acoustic representations used as input features for the LPCNet. The proposed autoregressive structure enables our system to produce the following prediction step outputs from the acoustic features predicted in the previous step. We evaluate the effectiveness of our system by performing any-to-one conversion pairs between native English speakers. Experimental results show that the proposed method outperforms state-of-the-art systems, producing higher speech quality and greater speaker similarity.

Non-alcoholic fatty liver disease (NAFLD) affects up to a quarter of the adult population in many developed and developing countries. This spectrum of liver disease ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The incidence of NASH is projected to increase by up to 56% over the next 10 years. There is growing epidemiological evidence that NAFLD has become the fastest growing cause of hepatocellular carcinoma (HCC) in industrialized countries. The annual incidence of HCC varies between patients with NASH cirrhosis and patients with noncirrhotic NAFLD. In this review, NAFLD/NASH-associated HCC will be described, including its epidemiology, risk factors promoting hepatocarcinogenesis, and management of HCC in patients with obesity and associated metabolic comorbidities, including preventive strategies and therapeutic approaches to address this growing problem.

Pancreatic neuroendocrine tumor (P-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional P-NETs, typically when liver metastases occur. NETs diagnosis is frequently late, along with symptoms related to hormone hypersecretion. We described the case of a patient with a low-grade non-functional P-NET, but with a typical clinical presentation of a carcinoid syndrome; moreover, we reviewed the literature regarding this topic. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hypervascular mass; then a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum Chromogranin A and urinary 5-HIAA measurements resulted negative. Given the small size of the lesion (8 mm), we preferred to perform an endoscopic ultrasonography (EUS) with fine-needle biopsy (EUS-FNB), allowing the diagnosis of low-grade (G1) non-functional P-NET (NF-P-NET). Surgery was waived, while a follow-up strategy was chosen. Early recognition of P-NETs, although rare, is necessary to improve patient’s survival. EUS-FNB should be the protocol of choice for an early characterization of these tumors.

(1) Background: The COVID-19 pandemic had a devastating impact on the world, causing widespread illness and death. It is essential to focus on prevention strategies to limit the spread of the disease. Despite the advent of vaccines, maintaining a vigilant approach to prevention remains paramount. While vaccines are essential, they do not guarantee absolute immunity, and their protective effect may diminish over time; (2) Methods: We reviewed effective strategies to prevent COVID-19 transmission. We focused on me-ta-analyses (MA), literature reviews (LR) and the health care context. Various prevention measures and interventions were reviewed. Both es-tablished practices and unresolved issues were considered; (3) Results: Standard precautions (SP) as the cornerstone of infection control, with hand hygiene and mask use as key components. Debate about the relative importance of droplet versus aerosol transmission led to differences in recommendations between agencies at the onset of the pandemic. We have clarified the role of personal protective equipment (PPE), including eye protection. The effectiveness of masks in pre-venting transmission is reviewed. The use of surgical masks is recommended to prevent droplet transmission, while eye protection is recommended in combination with masks. Although data show some risk reduction, the clear superiority of N95/FFP2 over surgical masks remains unproven. In terms of room occupancy, ventilation is critical in reducing the risk of transmission in poorly ventilated environments. The use of negative pressure isolation rooms (NPIRs) is being investigated. The presence of viral RNA on surfaces does not necessarily indicate infectivity, and the risk of transmission by surface contact is low if surfaces are properly maintained and hand hygiene is practised regularly. Testing for SARS-CoV-2 in asymptomatic persons in healthcare settings may help prevent transmission; (4) Conclusions: Prevention of SARS-CoV-2 transmission requires a multifaceted approach, including reducing particle emissions from infected persons by wearing masks, eliminating aerosols by ventilation, ensuring physical separation, and protecting exposed persons with masks and eye protection.

Non-alcoholic fatty liver disease (NAFLD) has gained attention in the last few years due to its increasing prevalence worldwide becoming a global epidemic. This review aims to discuss the latest recommendations regarding diagnosis and treatment of NAFLD-associated HCC and the remaining challenges. Thus, there is a high amount of data derived from basic and clinical studies that revealed the molecular pathways which drive NAFLD-associated hepatocellular carcinoma (HCC). Based on these findings, new prevention, surveillance and treatment strategies are emerging. However, current data on treatment modalities in NAFLD-associated HCC are still scarce, but based on subgroup analysis results from non-NAFLD HCC studies are promising and could provide a basis for future research agenda to address NAFLD/NASH patients. Conclusion: Due to the pandemic proportions that NAFLD gained in the last few years, there is a high amount of data derived from basic and clinical studies that revealed the molecular path-ways which drive NAFLD-associated HCC. Based on these findings, new prevention, surveillance and treatment strategies could be developed at an individual level.

Organophosphate pesticides (OPs) are toxic substances that contaminate aquatic environments, interfere with the development of the nervous system, and induce Neurodevelopmental Toxicity (NDT) in animals and humans. The canonical mechanism of OP neurotoxicity involves the inhibi-tion of acetylcholinesterase (AChE), but other mechanisms non-AChE are also involved and not fully understood. We used network toxicology and molecular docking to identify molecular targets and toxicity mechanisms common to OPs. Targets related to diazinon-oxon, chlorpyrifos oxon, and paraoxon OPs were predicted using the Swiss Target Prediction and PharmMapper databases. Targets related to NDT were compiled from GeneCards and OMIM databases. In order to construct the protein-protein interaction (PPI) network, the common targets between OPs and NDT were imported into the STRING. Networks topological analyses identified EGFR, MET, HSP90AA1, and SRC as hub nodes common to the three OPs. Using Reactome pathway and gene ontology we found that signal transduction, axon guidance, cellular responses to stress, and glutamatergic signaling activation play key roles in OP-induced NDT.

Spectrally weighed irradiance on the corneal plane is often used to determine the visual and non-visual potency of light. Spectral irradiance or illuminance is measured with a diffuser in the so-called 2π geometry (i.e., a hemispheric measurement). Due to anatomical conditions, the human binocular field of view (FOV) does not correspond to a hemisphere but is occluded upwards and downwards. FOV-restricted measurements are scarce, however, and thus the error when using hemispheric measurements is yet to be determined. For our study, we designed and 3D printed FOV occlusions as attachments to spectral measurement devices. Measurements with and without the occlusion were taken in different lighting situations in the laboratory (light from different directions) and in real-world conditions (light typically from above). Our measurements show a reduction of visual and melanopic values due to the FOV occlusion ranging from negligible to over 60% for realistic scenarios. Further, the reduction was comparable for visual and melanopic parameters, as the distribution of light in the FOV was generally spectrally homogeneous. In the case of an exemplary and artificial laboratory situation, however, the melanopic daylight (D65) efficacy ratio changed by more than a factor of 2 only due to the FOV occlusion. Finally, head orientation showed a marked impact on all quantities. Our results reveal the potential for considerable error when just evaluating and comparing vertical, hemispheric measurements in experiments and non-visual lighting design projects. We thus encourage the (additional) use of a FOV occlusion for eye-level measurements in typical viewing directions and provide open-source 3D-print files.

We have implemented quantum modeling mainly based on Bohmian Mechanics to study time series that contain strong coupling between their events. Compared to time series with normal densities, such time series are associated with rare events. Hence, employing Gaussian statistics drastically underestimates the occurrence of their rare events. The central objective of this study is to investigate the effects of rare events in the probability densities of time series from the point of view of quantum measurements. For this purpose, we first model the non-Gaussian behavior of time series using the multifractal random walk (MRW) approach. Then, we examine the role of the key parameter of MRW, λ, which controls the degree of non-Gaussianity, in quantum potentials derived for time series. Our Bohmian quantum analysis shows that the derived potential takes some negative values in high frequencies (its mean values), then substantially increases, and the value drops again for rare events. Thus, rare events can generate a potential barrier in the high-frequency region of the quantum potential, and the effect of such a barrier becomes prominent when the system transverses it. Finally, as an example of applying quantum potential beyond the microscopic world, we compute quantum potentials for the S&amp;P financial market time series to verify the presence of rare events in the non-Gaussian densities and demonstrate deviation from the Gaussian case.

A new treatment option for cluster headache (CH) prevention is needed. Monoclonal antibodies (mABs) against calcitonin gene-related peptide (CGRP) ligands are used as a preventative treatment for migraine. Considering the CGRP’s role in the CH attack’s ignition and upkeep, fremanezumab and galcanezumab have been evaluated for CH preventative treatment. However, only high-dose (300 mg) galcanezumab was proven for episodic CH prevention. We herein report 3 cases of migraine and comorbid CH with previous failures of preventive treatments. The 2 cases were treated with fremanezumab and the one with non-high-dose galcanezumab. All 3 cases showed good results not only on migraine but also on CH attacks. Our report suggested the efficacy of CGRP-mABs for CH prevention. Our cases differed from the cases in the phase 3 trials of CGRP-mABs for CH prevention in the following 2 points. First, the patients had both migraine and comorbid CH. Second, the combined use of CGRP-mABs with preventative drugs for CH, such as verapamil and/or prednisolone, was performed. Future accumulation of real-world data may prove the efficacy of CGRP-mABs for CH prevention.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

Acute intense exercise causes significant oxidative stress and consequently an increase in total antioxidant capacity; however, the mechanisms and combined effects of intense exercise and smoking on oxidative stress among active and non-active smokers are not clear. The aim of this study was to investigate the effect of acute intense exercise on antioxidant enzyme activity responses in active and non-active individuals exposed to cigarette smoke. The study included 40 subjects who were equally classified as: smokers that did exercise (SE), smokers that did not do exercise (SnE), non-smokers that did exercise (NSE), and non-smokers that did not do exercise (NSnE). The adjusted Astrand test was used to exhaust the subjects. Salivary enzymes of peroxidase (POX), catalase (CAT), and superoxide dismutase (SOD) were measured, by spectrophotometry methods, at 3 different time points: pre-test (TP1), post-test (TP2), and one hour after finishing the test (TP3). Significant (p<0.05) group x time interactions were found for the three enzymes. Salivary POX, CAT and SOD increased in all groups from TP1 to TP2 and decreased from TP2 to TP3. Only the NSE showed a significant difference between TP1 to TP3 in POX and SOD by +0.011 ± 0.007 and +0.075 ± 0.02 (U/ml), respectively. The NSE showed significantly higher levels of POX, CAT and SOD in TP2 compared to the other groups. Furthermore, NSE and NSnE had higher levels of POX, CAT and SOD in TP1 and TP3 (p<0.05) compared with SE and SnE. Only in the NSnE, were no differences observed in CAT compared with SE and SnE in TP3. These results showed that the antioxidant level at rest and in the recovery time after the acute intense exercise was lower in SE and SnE compared with NSE and NSnE, suggesting that smoking habit may reduce the ameliorating effect of regular physical activity on acute exercise-induced oxidative stress.

The PI3K/mTOR signalling pathway plays a central role in the governing of cell growth, survival and metabolism. As such, it must integrate and decode information from both external and internal sources to guide efficient decision-making by the cell. To facilitate this, the pathway have evolved an intricate web of complex regulatory mechanisms and elaborate crosstalk with neighbouring signalling pathways, making it a highly non-linear system. Here, we describe the mechanistic biological details that underpin these regulatory mechanisms, covering a multitude of negative and positive feedback loops, feed-forward loops, competing protein interactions, and crosstalk with major signalling pathways. Further, we highlight the non-linear and dynamic network behaviours that arise from these regulations, uncovered through both computational and experimental studies. Given the pivotal role of the PI3K/mTOR network in cellular homeostasis and its frequent dysregulation in pathologies including cancer and diabetes, a coherent and systems-level understanding of the complex regulation and consequential dynamic signalling behaviours within this network is imperative for advancing biology and development of new therapeutic approaches.

Based on comprehensible non-parametric methods, estimates of crucial parameters that characterise the COVID-19 pandemic with a focus on the German epidemic are presented. Where appropriate, the estimates for Germany are compared with the results for seven other countries (FR, IT, US, UK, ES, CH, BR) to get an idea of the breadth of applicability and a relational understanding. Thereby, only prevalence data of daily reported new counts of diagnosed cases and fatalities provided by the Johns Hopkins University are used. Drawing on uncertain a priori knowledge is avoided. Specifically, we present estimates resulting from delay-time correlations for the duration from diagnosis to death being 13 days for Germany and Switzerland. The delay-time correlation applied to time series from other countries exhibit less pronounced peaks suggesting high variabilities for the corresponding time-to-death durations. With respect to the German data, the two time series of new cases and fatalities exhibit a strong coherence within the frequency range of interest, which backs our findings. Furthermore, based on the knowledge of this time lag between diagnoses and deaths, properly delayed asymptotic as well as instantaneous fatality-case ratios are calculated having superiority compared to the commonly published case-fatality rate. The temporal median of the instantaneous fatality-case ratio with proper delay of 13-days between cases and deaths for Germany turns out to be 0.02. Time courses of asymptotic fatality-case ratios are presented for other countries which substantially differ during the first half of the pandemic, however, converge to a narrow range with standard deviation 0.57% and mean 2.4%. Additionally, the time courses of instantaneous fatality-case ratios with optimal delay for the 8 exemplarily chosen countries are calculated and compared by means of the temporal medians. Similarly to the asymptotic fatality-case ratios, the differences are much smaller than expected from mass media reports. The basic reproduction number, R₀, for Germany is estimated to be between 2.4 and 3.4. The uncertainty stems from uncertain knowledge of the generation time. A delay autocorrelation shows resonances at about 4 days and 7 days, where the latter resonance is at least partially attributable to the sampling process with weekly periodicity. The calculation of the basic reproduction number is based on an evaluation of cumulative numbers of cases yielding time-dependent doubling times as an intermediate step. This allows to infer to the reproduction number during the early phase of onset of the epidemic. In a second approach, the instantaneous reproduction number is derived from the incident (counts of new) cases and allows, in contrast to the first version, to infer to the temporal behaviour of the reproduction number during the later epidemic course. The time course of the reproduction number is compared to an alternative control measure given by the per capita growth, which largely confirms the conclusions drawn from the reproduction number. To conclude, by avoiding complicated parametric models we provide insights into basic features of the COVID-19 epidemic in an utmost transparent and comprehensible way. The perhaps most striking insight is that the fatality-case ratios do not differ between countries as much as previously suspected.

This paper focuses on the characterization approach to evaluate the decay state of Pietra Serena of historic buildings in Florence (Italy). Pietra Serena is a Florentine sandstone largely used in the city especially during the Renaissance; it is a symbol of cultural heritage of Florence and constitutes a large part of the city center, which was named a World Heritage Site by UNESCO in 1982. Unfortunately, many environmental factors negatively affect the stone, increasing damage and the danger of falling material. Any detachment of stone fragments, in addition to constitute a loss in cultural heritage, can be dangerous for citizens and the many tourists that visit the city. The use of Non-Destructive Techniques (NDTs) as ultrasonic and Schmidt hammer tests can quantitatively define some mechanical properties and help to monitor the decay degree of building stone. In this study, the NDTs were combined with mineralogical, petrographical, chemical and physical analyses to investigate the stone materials, in order to correlate their features with the characteristics of the different artefacts in Pietra Serena. Correlations between the NDTs results and the compositional characteristics of the on-site stone were carried out; such discussion allows to identify zones of weakness and dangerous unstable elements.

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5'end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5’ terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I or MDA5 receptors, a way to overcome antiviral innate immune response. Overall, natural 5′ terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host-cell interactions driving the development of acute or persistent EV-B infections.

Central nervous system (CNS) uses vision, vestibular, and somatosensory information to maintain body stability. Research has shown that there is more lumbar proprioception error among low back pain (LBP) individuals as compared to healthy people. In this study, two groups of 20 healthy people and 20 non-specific low back pain participants (LBP) took part in this investigation. This investigation focused on somatosensory sensors and in order to alter proprioception, a vibrator (frequency of 70Hz, amplitude of 0.5 mm) was placed on the soleus muscle area of each leg and two vibrators were placed bilaterally across the lower back muscles. Individuals, whose vision was occluded, were placed on two surfaces (foam and rigid) on force plate, and trunk angles were recorded simultaneously. Tests were performed in 8 separate trials; the independent variables were vibration (4 levels) and surface (2 levels) for within subjects and 2 groups (healthy and LBP) for between subjects (4×2×2). MANOVA and multi-factor ANOVA tests were done. Linear parameters for center of pressure (COP) (deviation of amplitude, deviation of velocity, phase plane portrait (PPP), and overall mean velocity) and nonlinear parameters for COP and trunk angle ((recurrence quantification analysis) RQA and Lyapunov exponents) were chosen as dependent variables. Results indicated that NSLBP individuals relied more on ankle proprioception for postural stability. Similarly, RQA parameters for the COP on both sides and for the trunk sagittal angle indicated more repeated patterns of movement among the LBP cohort. Analysis of short and long Lyapunov exponents showed that people with LBP caused no use of all joints in their bodies (non-flexible), are less stable than healthy subjects.

The behaviour of oxidized and non-oxidized multiwalled carbon nanotubes in the adsorption of lanthanum(III) from aqueous solutions is described. Metal uptake is studied as a function of several variables such as the stirring speed of the system, pH of the aqueous solution and metal and nanomaterial concentrations. The experimental results are fitted to various kinetics and isotherm models, being the rate law fitted to the film diffusion and particle diffusion models, when the non-oxidized and the oxidized nanomaterials are used to remove lanthanum from the solution, respectively. Sulphuric acid solutions seem to be appropriate to recover the metal from La-loaded nanomaterials.

After the increasing number of SARS-CoV-2 infections all over the world, researchers and clinicians are struggling to find a vaccine or innovative therapeutic strategies to treat this viral infection. The SARS-CoV infection that occurred in 2002, MERS and other more common infectious diseases such as HCV, led to the discovery of many RNA-based drugs. Among them, siRNAs and antisense LNAs have been demonstrated to have effective antiviral effects both in animal models and humans. Owing to the high genomic homology of SARS-CoV-2 and SARS-CoV (80-82%) the use of these molecules could be employed successfully also to target this emerging coronavirus. Trying to translate this approach to treat COVID-19, we analyzed the common structural features of viral 5’UTR regions that can be targeted by non-coding RNAs and we also identified miRNAs binding sites suitable for designing RNA-based drugs to be employed successfully against SARS-CoV-2.

This work promotes new methods in Mathematical Modeling, consisting in the use of the methods of Non-standard Analysis in Topoi, having as its main purpose, the mathematical definitions of the pseudoparticles from the title, with arguments from Biology/Physiology (Mathematical Neuroscience), Physics (String Theory and Emergent Quantum Mechanics), and Cybernetics (Global Brain, including Natural and Artificial Intelligence). The connections between brain and mind will be scketched via the genetic/epigenetic interplay. The topoi model the intuitionistic logic (multi-valued) and have been used in Quantum Physics while Non-Standard Analysis in SET (= the Category of sets) has been applied in Mathematical Economics; topics from Theory of Categories were also used in the study of Consciousness; however, the combination topoi - non-standard analysis was never used until now in Applied Mathematics. Another important objective is to produce progress in this aria of Pure Mathematics also - the build of non-standard analysis in classes of topoi, already used in Physics. We propose the logic of non-standard extensions in topoi as a model of the human thinking (based on infons/receptons), these theories representing new top and very difficult results in Abstract Mathematics either.

The present paper aims to increase knowlodge of the methods of resistance estimating of concrete in situ by means of non-destructive tests used to integrate the quantitative results from cylindrical specimens (core). The results of experimental investigations carried out on concrete conglomerate samples of a school building are shown. The experimental campaign then will be presented like a case study, conducted on a series of concrete beams and pillars of an existing building. The distructive tests on cores were conducted at the Civil Structures Laboratory of the Engineering Department of the University of Campania "Luigi Vanvitelli". The expression obtained through the calibration procedure of the values of non-destructive tests with those provided by the core drills allowed to estimate the average values of the compressive strength of the concrete. It is highlighted how this result was achieved with a very limited core number provided that they are extracted in selected points and that there was a proportionality link with the resistances obtained from non distructive tests.

A transport process was studied from an aqueous solution containing oxalic acid and 100 mg/L Ge using a flat sheet supported liquid membrane (FSSLM) system. Cyanex 923 immobilized in a polytetrafluoroethylene membrane was employed as a carrier. The solution chemistry and related diagrams were applied to study the transport of germanium. The effectual parameters such as oxalic acid, carrier concentration, and strip reagent composition were evaluated in this study. Based on the results, the oxalic acid concentration of 0.075 mol/L and the carrier concentration of 20 %v/v were the condition in which the efficient germanium transport occurred. Among strip reagents, NaOH (0.04-0.1 mol/L) had the best efficiency to transport germanium through the SLM system. Furthermore, the permeation model was obtained to calculate the mass transfer resistances of the membrane (Δ_m) and feed (Δ_f) phases. According to the results, the values of 1 and 1345 s/cm were evaluated for Δ_m and Δ_f, respectively.

Expressed sequenced tagged-polymerase chain reaction (EST-PCR) molecular markers were used to evaluate the genetic diversity of lowbush blueberry across its geographic range and to compare genetic diversity among four paired managed/non-managed populations. Seventeen lowbush blueberry populations were sampled in a general north south transect throughout eastern United States with distances between 27 km to 1600 km separating populations. Results show that the majority of genetic variation is found within populations (75%) versus among populations (25%), and that each population was genetically unique (P ≤ 0.0001) with the exception of the Jonesboro, ME and Lubec, ME populations that were found not to be significantly different (P = 0.228). The effects of management for commercial fruit harvesting on genetic diversity were investigated in four locations in Maine with paired managed and non-managed populations. Significant differences were found between the populations indicating that commercial management influences the genetic diversity of lowbush blueberries in the landscape, despite the fact that planting does not occur; forests are harvested and the existing understory blueberry plants are what become established.

Flow and transport processes in soil and rock play a critical role in agricultural non-point source pollution (ANSP) loads. In this study, we investigated the ANPS load discharged into rivers from an irrigation district in the Tibetan Plateau, and simulated ANPS load using a distributed model involving detailed descriptions of flow and ANPS transport and transformation processes in the soil and rock. Experiments were conducted for two years to measure soil water content and nitrogen concentrations and the quality and quantity of lateral flow in the rock and at the drainage canal outlet during the highland barley growing period. A distributed model, in which the subsurface lateral flow was described using a step-wise method, was developed to simulate flow and ammonium nitrogen and nitrate nitrogen transport. Sobol’s method was used to evaluate the sensitivity of simulated flow and transport processes to model inputs. The results showed that, with a 21.2% increase of rainfall and irrigation in the highland barley growing period, the average NH4+-N and NO3--N concentrations in the soil layer decreased by 10.8% and 14.3%, respectively, due to increased deep seepage. Deep seepage of rainfall water accounted for 0–52.4% of total rainfall, whereas deep seepage of irrigation water accounted for 36.6–45.3% of total irrigation. NH4+-N and NO3--N discharged into the drainage channel represented 19.9–30.4% and 19.4–26.7% of the deep seepage, respectively. The mean Nash-Sutcliffe coefficients, root mean square errors, and cumulative deviations between the measured and simulated flow rates and NH4+-N and NO3--N concentrations at the surface drainage canal outlet were 0.694, 0.081, and 0.242, respectively, indicating that the proposed method can effectively describe the hydrological and ANPS pollution migration in the plateau irrigation zone. The Sobol’ sensitivity analysis results demonstrated that subsurface lateral flow had the most important first order and total effect on the simulated flow and NH4+-N and NO3--N concentrations at the surface drainage outlet.

In this work, we report the magnetocaloric effect (MCE) in two systems of non-interactive particles, the first corresponds to the Landau problem case and the second, the case of an electron in a quantum dot subjected to a parabolic confinement potential. In the first scenario, we realize that the effect is totally different from what happens when the degeneration of a single electron confined in a magnetic field is not taken into account. In particular, when the degeneracy of the system is negligible, the magnetocaloric effect cools the system, while in the other case, when the degeneracy is strong, the system heats up. For the second case, we study the competition between the characteristic frequency of the potential trap and the cyclotron frequency to find the optimal region that maximizes the ΔT of the magnetocaloric effect, and due to the strong degeneration of this problem, the results are in coherence with those obtained for the Landau problem. Finally, we consider the case of a transition from a normal MCE to an inverse one and back to normal as a function of temperature. This is due to the competition between the diamagnetic and paramagnetic response when the electron spin in the formulation is included.

Running on a non-motorized, curved-deck treadmill is thought to improve gait mechanics. It is not known, though, if the change in gait carries over to running on a motorized treadmill or level ground. To determine the effect of running on a curved non-motorized treadmill (CNT) on gait characteristics measured during a subsequent bout of running on a traditional motorized treadmill (TMT). Sixteen healthy college-aged participants, age (mean±SD) 20.4±1.6 years volunteered to have their gait analyzed while running on a TMT and CNT. After familiarization and warm-up on both treadmills, each subject completed five, 4-minute bouts of running alternating between traditional motorized and curved non-motorized treadmills: TMT-1, CNT-1, TMT-2, CNT-2, and TMT-3. Variables of interest included step length (m), stride length (m), imbalance score (%), and step angle (°) and were measured using Optogait gait analysis equipment. Differences in gait char acteristics among TMT-1, TMT-2, and TMT-3 can be attributed to running on the CNT. The results show that running on a CNT resulted in significant changes in gait characteristics. These findings suggest that running on a CNT can significantly alter gait characteristics may result in improvements in running gait that persist to subsequent running on a TMT.

The ErbB/HER family of protein-tyrosine kinases (ErbB) and the phosphatidylinositol 3-kinase (PI3K) represent crucial targets in the treatment of head and neck squamous cell carcinoma (HNSCC). We previously reported that a combination therapy using Afatinib (ErbB inhibitor) and Copanlisib (PI3K inhibitor), both FDA-approved kinase inhibitors, suppressed the growth of HPV-positive HNSCC. In our current study, we further evaluated the efficacy and clinical potential of this combination therapy for treating HPV-negative HNSCC in vitro and in animal model. We found that the combination treatment of Afatinib and Copanlisib dramatically enhanced inhibition of cell proliferation and reduced cell survival when compared to treatment with either inhibitor in two HPV negative HNSCC cell lines. Notably, this combination led to significant inhibition of xenograft tumor growth in mice, without any apparent effects on body weight. Copanlisib alone effectively blocked PI3K/Akt signaling, but caused up-regulation of HER2 and HER3 phosphorylation as previously reported in other types of cancer. However, the combination treatment with Copanlisib and Afatinib completely blocked phosphorylation of the ErbB family (including HER3) and Akt, while also remarkedly increasing apoptosis. These results suggest that co-targeting the ErbB family and PI3K kinases by a combination treatment of Afatinib and Copanlisib can have clinical potential for patients.

Colletotrichum higginsianum is a major pathogen causing anthracnose in Chinese flowering cabbage (Brassica parachinensis), posing a significant threat to the Chinese flowering cabbage industry. The conidia of C. higginsianum germinate and form melanized infection structures called appressoria, which enable penetration of the host plant's epidermal cells. However, the molecular mechanism underlying melanin biosynthesis in C. higginsianum remains poorly understood. In this study, we identified two enzymes related to DHN-melanin biosynthesis in C. higginsianum: ChPks and ChThr1. Our results demonstrate that the expression levels of genes ChPKS and ChTHR1 were significantly up-regulated during hyphal and appressorial melanization processes. Furthermore, knockout of the gene ChPKS resulted in a blocked DHN-melanin biosynthetic pathway in hyphae and appressoria, leading to increased sensitivity of the ChpksΔ mutant to cell wall interfering agents as well as decreased turgor pressure and pathogenicity. It should be noted that although the Chthr1Δ mutant still exhibited melanin accumulation in colonies and appressoria, its sensitivity to cell wall interfering agents and turgor pressure decreased compared to wild-type strains; however, complete loss of pathogenicity was not observed. In conclusion, our results indicate that DHN-melanin plays an essential role in both pathogenicity and cell wall integrity in C. higginsianum. Specifically, ChPks is crucial for DHN-melanin biosynthesis while deficiency of ChThr1 does not completely blocked melanin production.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Although prognosis continually improved along years, a significant proportion of patients still relapse from the disease due to leukemia resistance to therapy. Methotrexate (MTX), a folic acid antagonist, is a chemotherapy agent commonly used against ALL and a immune-system suppressant for rheumatoid arthritis, that presents multiple and complex mechanisms of action and resistance. Previous studies have shown that MTX modulates the nuclear factor kappa B (NF-κB) pathway, an important family of transcription factors involved in inflammation, immunity, cell survival, and proliferation, frequently hyperactivated in ALL. Using gene set enrichment analysis (GSEA) on publicly available gene expression data from 161 newly diagnosed pediatric ALL patients, we found “TNF-α signaling pathway” to be the most enriched Cancer Hallmark in MTX poor responder patients. Transcriptomic analysis in a panel of ALL cell lines (6 BCP-ALL and 7 T-ALL) also identified the same pathway as differentially enriched among MTX resistant cell lines, as well as in slowly dividing cells. To better understand the crosstalk between NF-κB activity and MTX resistance, we genetically modified the cell lines to express luciferase under a NF-κB biding site promoter. We observed that the fold change in NF-κB activity triggered by TNF-α (but not MTX) treatment correlated with MTX resistance and proliferation across the lines. At the individual gene level, NFKB1 expression was directly associated with a poorer clinical response to MTX, and with both an increased TNF-α-triggered NF-κB activation and MTX resistance in the cell lines. Despite these results, pharmacological inhibition (with BAY 11-7082 and parthenolide) or stimulation (with exogenous TNF-α supplementation) of the NF-κB pathway did not alter MTX resistance of the cell lines significantly, evidencing a complex interplay between MTX and NF-κB in ALL.

Improving antigen presentation is crucial for the success of immunization strategies. Yeasts are classically used as biofactories to produce recombinant proteins and are efficient vehicles for the delivery of vaccine antigens, besides present adjuvants properties. Despite the absence of epidemic outbreaks, several vaccine approaches continue to be developed for Zika virus infection. These prophylactic strategies are fundamental given the severity of clinical manifestations, mainly due to viral neurotropism. The present study aimed to evaluate in vivo the immune response induced by P. pastoris recombinant strains displaying epitopes of the Envelope (ENV) and NS1 ZIKV proteins. Intramuscular immunization with heat-attenuated yeast enhanced the secretion of IL-6, TNF-α, and IFN-γ, besides activation of CD4+ and CD8+ T cells, in BALB/c mice. P. pastoris displaying ENV epitopes induced a more robust immune response, increasing immunoglobulin production, especially IgG isotypes. Both proposed vaccines showed the potential to induce immune responses without adverse effects, confirming the safety of administering P. pastoris as a vaccine vehicle. Here we demonstrated, for the first time, the evaluation of a vaccine against ZIKV based on a multiepitope construct, using yeast as a vehicle, reinforcing the applicability of P. pastoris as a whole yeast cell vaccine.

Background: Methadone is a centrally-acting synthetic opioid analgesic widely used in the methadone maintenance therapy (MMT) programs throughout the world. Considering its neurotoxic effects particularly on the cerebellum, this study aims to address the behavioral and histological alterations in the cerebellar cortex associated with methadone administration. Materials and Methods: Twenty-four adult male albino rats were randomized into two groups of control and methadone treatment. Methadone was subcutaneously administered (2.5–10 mg/kg) once a day for two consecutive weeks. The functional and structural changes in the cerebellum were compared to the control group. Results: Our data revealed that treating rats with methadone not only induced cerebellar atrophy, but also prompted the actuation of microgliosis, astrogliosis, and apoptotic biomarkers. We further demonstrated that treating rats with methadone increased complexity of astrocyte processes and decreased complexity of microglia processes. Our result showed that methadone impaired motor coordination and locomotor performance and neuromuscular activity. Additionally, relative gene expression of TNF-α, caspase-3 and RIPK3 increased significantly due to methadone. Conclusions: Our findings suggest that methadone administration has a neurodegenerative effect on the cerebellar cortex via dysregulation of microgliosis, astrogliosis, apoptosis, and neuro-inflammation.

Among non-conventional yeasts of industrial interest, the dimorphic oleaginous yeast Yarrowia lipolytica appears as one of the most attractive for a large range of white biotechnology applications, from heterologous proteins secretion to cell factories process development. The past, present and potential applications of wild type, traditionally improved or genetically modified Yarrowia lipolytica strains will be resumed, together with the wide array of molecular tools now available to genetically engineer and metabolically remodel this yeast. The present review will also provide a detailed description of Yarrowia lipolytica strains and highlight the natural biodiversity of this yeast, a subject little touched upon in most previous reviews. This work intends to fill this gap by retracing the genealogy of the main Yarrowia lipolytica strains of industrial interest, by illustrating the search for new genetic backgrounds and by providing data about the main publicly available strains in yeast collections worldwide. At last, it will focus on exemplifying how advances in engineering tools can leverage a better biotechnological exploitation of the natural biodiversity of Yarrowia lipolytica and of other yeasts from the Yarrowia clade.

Wolbachia are intracellular endosymbionts of several invertebrate taxa, including insects and nematodes. Although Wolbachia DNA has been detected in ticks, its presence is generally associated with parasitism by insects. To determine whether or not Wolbachia can infect and grow in tick cells, cell lines from three tick species, Ixodes scapularis, Ixodes ricinus and Rhipicephalus microplus, were inoculated with Wolbachia strains wStri and wAlbB isolated from mosquito cell lines. Homogenates prepared from fleas collected from cats in Malaysia were inoculated into an I. scapularis cell line. Bacterial growth and identity were monitored by microscopy and PCR amplification and sequencing of fragments of Wolbachia genes. The wStri strain infected Ixodes spp. cells and was maintained through 29 passages. The wAlbB strain successfully infected Ixodes spp. and R. microplus cells and was maintained through 2-5 passages. A novel strain of Wolbachia belonging to the supergroup F, designated wCfeF, was isolated in I. scapularis cells from a pool of Ctenocephalides sp. cat fleas and maintained in vitro through two passages over nine months. This is the first confirmed isolation of a Wolbachia strain from a flea and the first isolation of any Wolbachia strain outside the “pandemic” A and B supergroups. The study demonstrates that tick cells can host multiple Wolbachia strains, and can be added to panels of insect cell lines to improve success rates in isolation of field strains of Wolbachia.

Mammary neoplasm affects a population of intact and elderly female dogs and 50% are malignant. In order to study this disease, cell culture is as a promising preclinical model, creating the opportunity to deposit cell lines at a cell bank, allowing a great reproducibility of the assays and making the validation of the results more reliable. Another important aspect is the possibility to establish models for better understanding tumour characteristics, such as vasculogenic mimicry. Due the importance of cancer cell lines in preclinical models, this study aimed to establish and characterize primary cell lines from canine mammary gland tumours according to immunophenotype and tumorigenicity, and with its ability to form vasculogenic mimicry-like structures in vitro and in vivo. Cell cultures were evaluated for morphology, phenotype, vasculogenic mimicry and tumorigenicity abilities. We collected 17 primary mammary carcinoma and 3 metastasis and had a satisfactory result in 10 of them. All cell lines presented spindle shape or polygonal morphology and expressed concomitant pan-cytokeratin and cytokeratin 8/18. Four cell lines had vasculogenic mimicry ability in vitro and two of them showed in vivo tumorigenic potential and forming VM in the xenotransplant tumour. Cell characterization of those lines will help to create a database for more knowledge of mammary carcinomas in dogs, including studies of tumour behaviour and new therapeutic targets.

Val-Phe-Val-Arg-Asn (VFVRN) has been identified and screened from lipid-lowering chickpea peptides (ChPs) by using a pharmacokinetic model in our previous experiment. The present study was conducted to investigate its effects and mechanisms on lipid metabolism. A high-fat diet C57BL/6J mice model and 3T3-L1 preadipocyte cell model were used. VFVRN was found to significantly decrease the levels of some blood lipids. The expressions of LDL receptor (LDLR), peroxisome proliferator-activated receptors (PPAR)α, liver X receptor (LXR)α, cholesterol 7α-hydroxylase (CYP7A1) and AMP-activated protein kinase (p-AMPK) in liver were up-regulated by VFVRN treatment. The expressions of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), fatty acid synthetase (FAS), 1-aminocyclopropane-1-carboxylate synthetase (ACC), sterol regulatory element-binding protein (SREBP)-1c and SREBP-2 in liver were significantly (P<0.05) down-regulated. Additionally, the expressions of PPARα and PPARγ in adipose tissues were up-regulated by VFVRN significantly (P<0.05). VFVRN might also contribute to transintestinal cholesterol efflux (TICE) by up-regulating the expressions of LXRα and ATP binding cassette G5/8 transporters (ABGC5/8). Moreover, VFVRN promoted 3T3-L1 preadipocyte apoptosis by up-regulating the expressions of BaX, cleaved Caspase-3 and down-regulating Bcl-2. VFVRN had potent effects in reversing metabolic disorders of blood and liver in a high-fat diet mice model, as well as to promote the apoptosis of 3T3-L1 preadipocytes.

Praeruptorin A(PA), a naturally existing pyranocumarin, is isolated from the dried root of Peucedanum praeruptorum Dunn. So far the anti-cancer effect and molecular mechanism behind Praeruptorin A action in human cervical cancer HeLa cells remain unknown. In the present study, we find that PA reduces cell proliferation and colony formation of human cervical cancer HeLa cells through inducing cell cycle arrest at G0/G1 phase. PA-upregulated p21 and p27 proteins are observed, accompanied with inhibition of cyclin D1 and S-phase kinase-associated protein 2(Skp2) proteins expression. PA could significantly inhibit migration and invasion of human HeLa cells. Meanwhile, PA significantly reduces invasive protein expression of matrix metalloproteinase-2 (MMP-2), and increases protein expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). PA is observed to possess the capacity in suppressing ERK1/2 activation. PD98059 (ERK specific inhibitor) significantly enhances PA-induced downregulation of MMP-2 expression, and upregulation of TIMP-2 expression. Moreover, we found that PA treatment notably inhibits 12-O-tetradecanoylphorbol-13-acetate(TPA)-upregulated ERK1/2 activation, MMP-2 expression, cellular migration and invasion in human HeLa cells. Taken together, these findings are the first to demonstrate the anti-cancer activity of PA, which may act as a promising therapeutic agent for the treatment of human cervical cancer.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

Alzheimer's disease (AD), the most common neurodegenerative disease and the first cause of dementia worldwide, has no effective treatment yet, and AD's pathological mechanisms are not yet fully understood. We conducted this study to explore the proteomic differences associated with Familial Alzheimer's Disease (FAD) in olfactory ecto-mesenchymal stem cells (MSCs) derived from PSEN1 (A431E) mutation carriers compared with healthy donors paired by age and gender through two label-free liquid chromatography-mass spectrometry approaches. The first analysis compared carrier 1 (patient with symptoms, P1) and its control (healthy donor, C1), and the second the Carrier 2 (patient with pre-symptoms, P2) with its respective control cells (C2) to evaluate whether the protein alterations presented in the symptomatic carrier were also present in pre-symptoms stages. Finally, we analyzed the differential expressed proteins (DEPs) for biological and functional enrichment. These proteins showed an impaired expression in a stage-dependent manner and are involved in energy metabolism, vesicle transport, actin cytoskeleton, cell proliferation, and proteostasis pathways resembling previous AD reports. Our study is the first proteomic analysis in MSCs from FAD patients in two stages of the disease (symptomatic and presymptomatic), showing these cells as a new and excellent in vitro model for future AD studies.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

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

Aggressive mature T-cell lymphoma (TCL) is a disease that carries a poor prognosis. The mechanism, at the functional protein level, of the resistance to therapy of TCL has not yet been well clarified. To comprehensively clarify the mechanism, we first reviewed the literature, as mentioned in the Introduction section, on 22 types of representative functional proteins reported as being potentially associated with treatment resistance, mainly in hematologic tumors. Next, we retrospectively analyzed the tumor cell expressions of these 22 functional proteins in 16 randomly selected patients with TCL who had received CHOP (cyclophosphamide, hydroxyl doxorubicin, oncovin, and prednisolone) therapy as first-line treatment. As a result, we propose a new three-group prognostic classification of TCL (the TCL Urayasu Classification) based on the mechanism of resistance to treatment of these tumors. The study subjects included 7 patients (44%) with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), 6 patients (38%) with angioimmunoblastic T-cell lymphoma (AITL), and 3 patients (19%) with anaplastic large T-cell lymphoma (ALCL). Immunohistochemistry was performed in paraffin-embedded tumor tissue sections prepared from these patients as antigens using antibodies against the 22 previously reported treatment-resistance-related proteins to determine the tumor cell expression statuses of these proteins. Log-rank test was performed to compare the overall survival (OS) after CHOP therapy of the patients showing positive and negative immunostaining for these proteins, as well as among patients grouped based on other factors. Overall, the median OS of the TCL patients was about 33.5 months. When compared by the disease type, the prognosis was found to be worse in the order of ALCL, AITL, and PTCL. A multivariate analysis showed that expression of glucose-regulated protein 94 (GRP94), a protein that serves as a pro-survival component under endoplasmic reticulum (ER) stress in the tumor microenvironment, was significantly associated with shortened survival. No significant difference was observed for the conventional poor prognostic factors: high-risk International Prognostic Index (IPI) and high-risk Prognostic Index for peripheral T-cell lymphoma, unspecified (PTCL-U) (PIT). However, when GRP94 was combined with six other factors, listed below, as survival-shortening factors, significant differences were observed. The 6 factors were 1) programmed cell death-ligand 1 (PD-L1) and 2) programmed cell death 1 (PD-1), which are involved in immune surveillance; 3) aldo-keto reductase family 1 member C3 (AKR1C3), which is an enzyme that inactivates HO (hydroxyl doxorubicin [H] and oncovin [O]) of CHOP; 4) P53, a tumor suppressor; 5) Glucose-regulated protein 78 (GRP78), an ER stress protein; 6) thymidine phosphorylase (TP), which is an enzyme involved in thymidine catabolism. Based on the combination of GRP94 and the six other factors expressed in the tumors, we propose a new prognostic classification system for TCL (TCL Urayasu classification). Group 1 (group with a relatively good prognosis): GRP94-negative (n = 6; median OS, 88 months; p < 0.01); Group 2 (group with a poor prognosis): GRP94-positive, plus expression of 2 of the 6 aforementioned factors (n = 5; median OS, 25 months; p > 0.05); and Group 3 (group with a very poor prognosis): GRP94-positive, plus expression of at least 3 of the 6 aforementioned factors (n = 5; median OS, 10 months; p < 0.01). Thus, the TCL Urayasu prognostic classification is a simple, useful, and innovative classification that also explains the mechanism of resistance to treatment for each functional protein. Accumulation of more cases and further analyses are expected in the future to enable clinical application, such as use of a stratified treatment approach and treatment using inhibitors.

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

Currently there are fewer depth models applied to pepper picking detection, while the existing generalized neural networks have problems such as large model parameters, long training time, and low model accuracy.In order to solve the above problems, this paper proposes a Yolo-chili target detection algorithm for chili pepper detection. First, the classical target detection algorithm yolov5 is used as a benchmark model, and an adaptive spatial feature pyramid structure combining the attention mechanism and the idea of multi-scale prediction is introduced to improve the model's detection effect on occluded peppers and small target peppers. Secondly, a three-channel attention mechanism module is introduced to improve the algorithm's long-distance recognition ability and reduce the interference of redundant testers. Finally, the quantized pruning method is used to reduce the model parameters and realize the lightweight processing of the model. Applying the method to the homemade chili pepper dataset, the AP value of chili pepper reaches 93.11%; the accuracy rate is 93.51% and the recall rate is 92.55%.The experimental results show that yolo-chili is able to achieve accurate and real-time pepper detection under complex orchards.