In this study, a new approach to pesticide permeation through the apple peel into the pulp is discussed. The tested compounds can be classified, based on mode of action, as systemic (boscalid, cyprodinil, pirimicarb, propiconazole and tebuconazole) or contact (captan, cypermethrin and fludioxonil) pesticides. The barrier effect was assessed using a Franz flow-type vertical diffusion cell system. Residue analysis was performed using a modified quick, easy, cheap, efficient, rugged and safe (QuEChERS) extraction method coupled to gas chromatography with tandem mass spectrometry (GC-MS/MS). The limits of detection (LODs) ranged between 2.6 µg kg-1 (pirimicarb) and 17 µg kg-1 (captan), with the coefficient of variability (CV) lower than 6%, while recoveries ranged from 85% (boscalid) to 112% (captan) at 0.1 and 1 mg kg-1 spiked levels. The highest peel penetration was observed for pirimicarb, captan and cyprodinil, with cumulative permeation of 90, 19 and 17 µg cm-2, respectively. The total absorption was in the range from 0.32% (tebuconazole) to 32% (pirimicarb). Only cypermethrin was not quantitatively detected in the pulp and its use can be recommended in crop protection techniques. The obtained results indicate that molecular weight, octanol-water partition coefficient and water solubility are important parameters determining the process of pesticide absorption.

A major parameter controlling the extent and rate of oral drug absorption is permeability through the lipid bilayer of intestinal epithelial cells. Here, a biomimetic artificial membrane permeability assay (Franz-Bampa) was validated using Franz cells apparatus. Both high and low permeability drugs (metoprolol and mannitol, respectively) were used as external standards. Biomimetic properties of Franz-Bampa were also characterized by electron paramagnetic resonance spectroscopy (EPR). Moreover, the permeation profile for the 14 BCS class I-IV drugs cited in the FDA guidance (including other drugs as acyclovir, cimetidine, diclofenac, ibuprofen, piroxicam, and trimethoprim) were measured across Franz-Bampa. Apparent permeability (Papp) was compared to literature fraction dose absorbed in humans (Fa%). Papp in Caco-2 cells and Corti artificial membrane were likewise compared to Fa% to assess Franz-Bampa performance. Mannitol and metoprolol Papp values across Franz-Bampa were lower (3.20 x 10-7 and 1.61 x 10-5 cm/s, respectively) than those obtained across non-impregnated membrane (2.27 x 10-5 and 2.55 x 10-5 cm/s, respectively), confirming lipidic barrier resistivity. Performance of the Franz cell permeation apparatus using an artificial membrane showed similar log linear correlation (R2 = 0.664) with Fa%, as seen for Papp in Caco-2 cells (R2 = 0.805). Data support the validation of the Franz-Bampa method for use during drug discovery process.

Acute and chronic graft versus host disease (a/cGVHD) are major complications of allogeneic stem cell transplantation and a frequent cause of non relapse-mortality. The treatment of a/cGVHD consists of steroid administration at full dose. In the case of aGVHD, around 60 % of patients with grade III/IV fails to respond (steroid-resistant, SR), requiring a second line therapy. Extracorporeal photopheresis (ECP) represents a good option for second line treatment, leading to multiorgan response in several patients. Here, we have evaluated the performances of a cytofluorimetric quality control of the first ECP procedure in 29 patients with severe SR aGVHD who underwent ECP. The quality control represents a check control of in vitro cell apoptosis/death induction in collected and irradiated CD3+ cells by ECP. Our analysis shows that in more than 70 % quality controls a relevant apoptotosis/death of CD3+ cells was observed after cell irradiation, as compared to non-irradiated controls. Albeit observed in a small patients’ series, the occurrence of relevant in vitro effect after ECP relates to less procedures and/or to a better survival on ECP. Age, disease, gender, aGVHD grade and time from transplant to the first ECP had not impact on ECP efficacy in this patients’ series.

Shigella and Salmonella have been implicated in neonatal sepsis, food poisoning, and bacteremia. Their increasing resistance to antibiotics has undermined treatment options, constituting a public health crisis. Also, the scarcity of new antibiotics in the development pipeline compounds multidrug-resistance (MDR). Hence, there is a need to potentiate antibiotics to mitigate resistance. This study leveraged riboflavin to re-sensitize fluoroquinolones and carbapenems against MDR Shigella and Salmonella spp. Disk diffusion, microbroth-dilution, chequerboard, and time-kill assays were used to determine resistance profiles and riboflavin-antibiotic activity. Biofilm-formation and bacterial viability (after riboflavin-antibiotic challenge) was determined with crystal-violet and Macrophage infection assays, respectively. Strains exhibited >80% resistance to fluoroquinolones and carbapenems, with 160–320 µg MIC ranges and 0.5–2 FIC, indicating no synergy. At 40–80 µg riboflavin, there was two-fold reduction in bacterial survival, with meropenem-riboflavin exhibiting significant reduction and FIC of 0.075 indicating high synergistic activity. Biofilm-formation was altered (from strong to weak phenotype) with 40 µg riboflavin-antibiotic treatment. There was a 40–70% reduction in bacterial survival in THP-1 cells treated with meropenem-riboflavin after 3 hours, and complete clearance between 24-48 hpi. Riboflavin potentiated fluoroquinolones and meropenem, leading to modulation of the host immune response for the clearance of the strains.

Plant cells' ability to withstand abiotic stress is strongly linked to modifications in their mechanical characteristics. Nevertheless, the lack of a workable method for consistently tracking plant cell mechanical properties severely restricts our comprehension of the mechanical alterations in plant cells under stress. With Polyethylene Glycol (PEG6000), we created a drought-like environment, and we used the Double Resonator Piezoelectric Cytometry (DRPC) method to dynamically and non-invasively track changes in the stress (ΔS) created and viscoelasticity (storage modulus G' and loss modulus G") of protoplasts and suspension cells of rice during drought stress. The findings demonstrate that, rice suspension cells and protoplasts react mechanically differently to 5%–15% PEG6000 stress, implying distinct resistance mechanisms. However, neither of them can withstand 25% PEG6000 stress, they respond mechanically similarly to 25% PEG6000 stress. The results of DRPC are further corroborated by the morphological alterations of rice cells and protoplasts observed under an optical microscope. To sum up, the DRPC technique functions as a precise cellular mechanical sensor and offers novel research tools for the evaluation of plant cell adversity and differentiating between the mechanical reactions of cells and protoplasts under abiotic stress.

Cell-culture meat is a novel concept to replace traditional meat produced from animals, and to satisfy rising food demands due to the world population growth. It is still a young field and requires to solve technical issues including cell sources and types, efficient culture for large scale production, taste and texture for customer satisfaction. The current review summarized traditional beef meat production and evaluation methods for customer satisfaction. In particular, serum biomarkers for beef meat evaluation are discussed, which can be applicated for cell-culture meat production.

Reconstructing the Tree of Life remains a central goal in biology. Early methods, relying on small numbers of morphological or genetic characters, often yielded conflicting evolutionary histories, undermining confidence in the results. Investigations based on phylogenomics, which use hundreds to thousands of loci for phylogenetic inquiry, have provided a clearer picture of life's history, but certain branches remain problematic. To resolve difficult nodes on the Tree of Life, two recent studies tested the utility of synteny, the conserved collinearity of orthologous genetic loci in two or more organisms, for phylogenetics. Synteny exhibits compelling phylogenomic potential while also raising new challenges. We identify and discuss specific opportunities and challenges that bear on the value of synteny data and other rare genomic changes for phylogenomic studies. Synteny-based analyses of highly contiguous genome assemblies mark a new chapter in the phylogenomic era and the quest to reconstruct the Tree of Life.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

This review considers the generation of relatively simple biomolecules, e.g., primary amino acids, resulting from the rapid collapse of bubbles in aqueous solutions containing various, low molar mass, gases. Some of the possible primary reactions occurring to produce the biomolecules are introduced and discussed. A brief discussion is included on the possible involvement of hydrodynamic cavitation, at the primordial seashore, as the initiating processes for the formation of the first organic molecules on prebiotic earth and the origins of life on Earth some 4 billion years ago.

In this study, the microbial strain was isolated from the humus soil to ferment Sophora flavescens and Eleutherococcus sessiliflorus extracts. The isolated microbial was identified as Bacillus genus by 16S rRNA sequence analysis. The fermented plant extracts exhibited the antifungal effects against four types of the plant pathogens such as P. carotorum, B. cinerea, C. fructicola Sau-3, and C. gloeosporioides according to incubation time. Especially, the fermented plant extracts showed the most active activities for Colletotrichum genus to inhibit mycelium growth. Metabolite changes in fermented S. flavescens and E. sessiliflorus extracts were confirmed through LC-Q-TOF/MS. Flavonoid and peptide derivatives were improved in fermented S. flavescens and E. sessiliflorus extracts compared to their unfermented one, respectively. This study suggested that the isolated Bacillus microbial fermentation could be a valuable tool in improving the bioactivity of S. flavescens and E. sessiliflorus extracts to have potential with more environmentally-friendly antifungal agents.

In wireless sensor networks (WSNs), each sensor node can estimate the global parameter from the local data in distributed manner. This paper proposed a robust diffusion estimation algorithm based on minimum error entropy criterion with self-adjusting step-size, which are referred to as diffusion MEE-SAS (DMEE-SAS) algorithm. The DMEE-SAS algorithm has fast speed of convergence and is robust against non-Gaussian noise in the measurements. The detailed performance analysis of the DMEE-SAS algorithm is performed. By combining the DMEE-SAS with diffusion minimum error entropy (DMEE) algorithms, an Improving DMEE-SAS algorithm is proposed, in non-stationary environment where tracking is very important. The Improving DMEE-SAS algorithm can avoid insensitivity of the DMEE-SAS algorithm due to the small effective step-size near the optimal estimator, and obtain a fast convergence speed. Numerical simulations are given to verify the effectiveness and advantages of these proposed algorithms.

When phenomena in quantum mechanics are interpreted from the perspective of bio-psychology, wave function collapse from several to a single eigenstate must be plausibly explained. Quantum mechanics requires a context, yet the context of an observer is rarely considered. On the other hand, in bio-psychology, the observer context is examined to explain superposition and collapse by different mental functions used in everyday life. Three mental functions are described, one of which is responsible for observation, and the others for conservation and treatment of information in mental representation. Whereas observation produces information with certainty, the subsequent processes result in uncertain potentiality. In order to encompass uncertainty, multiple possibilities are simultaneously considered in mental superposition, one of which should represent the unknown future outcome. During observation, all suggested potentialities necessarily collapse to one real outcome. The collapse of superposition does not occur in observable physical reality, but in its mental representation. Some physical principles—such as superposition, infinity and nothingness before the Big Bang—are pure phenomena of mental representation, which will always remain unverifiable by observation. This argument proves that mental representation brought about by the observer context participates in the production of mental models for the best approximation of physical reality.

Given the accelerating scientific, clinical and consumer interest in highly-prevalent functional gastrointestinal disorders, appropriate therapeutic strategies are needed to address the many aspects of digestive dysfunction. Accumulating evidence for the crucifer-derived bioactive molecule, sulforaphane in upstream cellular defence mechanisms highlights its potential as a therapeutic candidate in targeting functional gastrointestinal conditions together with systemic disorders. This article catalogues the evolution of and rationale for a hypothesis that utilises multifunctional sulforaphane as the initial step in restoring the ecology of the gut ecosystem; it does this primarily by targeting the functions of intestinal epithelial cells. A growing body of work has identified the colonocyte as the driver of dysbiosis, so that targeting gut epithelial function could provide an alternative to targeting the microbes themselves for remediation of microbial dysbiosis. The hypothesis discussed herein has evolved over several years and is supported by case studies showing the application of sulforaphane in gastrointestinal disorders, related food intolerance and several systemic conditions. To our knowledge, this is the first time the effects of sulforaphane have been reported in a clinical environment where several of its key properties within the gut ecosystem appear to be related to its nutrigenomic effects on gene expression.

Unsupervised physics-informed deep learning can be used to solve computational physics problems by training neural networks to satisfy the underlying equations and boundary conditions without labeled data. Parameters such as network architecture and training method determine the training success. However, the best choice is unknown a priori as it is case specific. Here, we investigated network shapes, sizes, and types for unsupervised physics-informed deep learning of the two-dimensional Reynolds-averaged flow around cylinders. We trained mixed-variable networks and compared them to traditional models. Several network architectures with different shape factors and sizes were evaluated. The models were trained to solve the Reynolds-averaged Navier-Stokes equations incorporating Prandtl's mixing length turbulence model. No training data were deployed to train the models. The superiority of the mixed-variable approach was confirmed for the investigated high Reynolds number flow. The mixed-variable models were sensitive to the network shape. For the two cylinders, differently deep networks showed superior performance. The best fitting models were able to capture important flow phenomena such as stagnation regions, boundary layers, flow separation, and recirculation. We also encountered difficulties when predicting high Reynolds number flows without training data

Knowledge is not merely the characteristic of certain pieces of information being deemed true and justifiable, but rather a process. Within an axiomatic system, the set of information that reaches the status of knowledge forms a universe that provides an interpretation of the reality one aims to describe. Language exchanges information through communication and the process of justification (exchange of information), if it consistently justifies a particular piece of information, it elevates it to knowledge. In this paper, we provide a framework for knowledge within an axiomatic model where we define the fundamental elements of communication and grammar. As a result, the structure dictates that knowledge, to be considered as such, must be investigateable by anyone who utilizes it in its entirety, both in form and content. Ultimately, the development of knowledge processing, referred to as \emph{knowmatics}, represents a clear evolution of the computer science that processes information (subset of knowledge).

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

Proteins need to be located in appropriate spatiotemporal contexts to carry out their diverse biological functions. Mislocalized proteins may lead to a broad range of diseases, such as cancer and Alzheimer’s disease. Knowing where a target protein resides within a cell will give insights into tailored drug design for a disease. As the gold validation standard, the conventional wet lab uses fluorescent microscopy imaging, immunoelectron microscopy, and fluorescent biomarker tags for protein subcellular location identification. However, the booming era of proteomics and high-throughput sequencing generates tons of newly discovered proteins, making protein subcel-lular localization by wet-lab experiments a mission impossible. To tackle this concern, in the past decades, artificial intelligence (AI) and machine learning (ML), especially deep learning methods, have made significant progress in this research area. In this article, we review the latest advances in AI-based method development in three typical types of approaches, including sequence-based, knowledge-based, and image-based methods. We also elaborately discuss existing challenges and future directions in AI-based method development in this research field.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

There is little doubt that final victories over pandemics, such as COVID-19, are attributed to herd immunity, either through post-disease convalescence or active immunization of a high percentage of the world's population with vaccines, demonstrating protection from infection and transmission, being available in large quantities and at reasonable prices. However, it is assumable that humans with immune defects or immune suppression, e.g., as a consequence of allograft transplantation, cannot be immunized actively nor produce sufficient immune responses to prevent SARS-CoV-2 infections. These subjects desperately need other strategies, such as sophisticated protection measures and active immunization. Hypertonic salt solutions attack vulnerable core areas of viruses, i.e., salt denatures surface proteins and thus prohibits virus penetration of somatic cells. It has to be ensured that somatic proteins are not affected by denaturation regarding this unspecific virus protection. Impregnating filtering facepieces with hypertonic salt solutions is a straightforward way to inactivate viruses and other potential pathogens. As a result of the contact of salt crystals on the filtering facepiece, these pathogens become denatured and inactivated almost quantitatively. Such a strategy could be easily applied to fight against the COVID-19 pandemic and other ones that may occur in the future. Another possible tool to fight the COVID-19 pandemic is passive immunization with antibodies against SARS-CoV-2, preferably from human origin. Such antibodies can be harvested from patients´ human sera, which have successfully survived their SARS-CoV-2 infection. The disadvantage of a rapid decrease of the immunoglobulin titer after infection ends can be overcome by immortalizing antibody-producing B-cells via fusion with, e.g., mouse myeloma cells. The resulting monoclonal antibodies are then of human origin and available in, at least theoretically, unlimited amounts. Finally, dry blood spots are a valuable tool for surveilling the population´s immunity.

Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: small duct type and large duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes–inflammation and proliferation–have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.

Background: Extracellular Vesicles are pivotal mediators in intercellular communication, facilitating the exchange of biological information among healthy, pathological and tumor cells. Between the diverse subtypes of extracellular vesicles, exosomes have unique properties, clinical and therapeutical applications, even towards cancer. Breast cancer ranks as one of the most prevalent malignancies across the globe. Both the tumor core and its surrounding microenvironment engage in a complex, orchestrated interaction that facilitates the cancer’s growth and spread. Methods: The most valuable and significant PubMed Literature about extracellular vesicles and adipose–derived stem cells exosomes was selected and analyzed in order to report their biological properties and potential applications, in particular on the Triple–Negative Breast Cancer. Results: Adipose–derived stem cells exosomes represent a potential tool to target the tumor core of the Triple–Negative Breast Cancer, its microenvironment and surrounding tissues including metastasis. The authors are developing a supportive Triple–Adipose–derived stem cells Exosomes [T.A.E.] Technology against breast cancer in order to perform a selective preconditioning of the cancer before or while the traditional oncological treatments are running. Conclusion: The possibility to exploit the impact of Adipose–derived stem cells exosomes within the T.A.E. Technology against the Triple–Negative breast cancer is real, highlighting a new era for supportive measures against breast cancer.Keywords: Extracellular vesicles; Exosomes; Adipose–derived stem cells, Tumor microenvironment, Triple–Negative Breast Cancer, T.A.E. Technology.

Transarterial chemoembolization (TACE) has been used to treat hepatocellular carcinoma (HCC) for more than 4 decades. So far, there is no consensus on which substances and which method should be used for the most effective treatment. A publication commissioned by CIRSE 2021 attempted to formulate recommendations. However, only the spectrum of currently implemented procedures is outlined. No recommendation was made as to how the various patients should be treated. In this article, therefore, basic considerations regarding the technique of chemoembolization are presented. Additionally, the authors discuss fundamental considerations about the embolism materials used, the cytostatic drugs and their dosage, as well as about pain therapy during treatment. Then, a technique is presented which used degradable starch microspheres (DSM) as an embolic agent. This technique allows multiple treatments over a longer period. The aim is to provide interventionalists with a decision-making aid for the TACE technique. A major problem when evaluating publications from different working groups is that the technology used is not adequately described and the individual studies are therefore not comparable. Therefore, a classification is presented that systematizes the possible different techniques. Future randomized trials should use this classification. Hopefully, if they are carried out on a sufficient number of patients, it will finally be possible to identify what is the best TACE procedure for individual patients. Until then the technique proposed by the authors can be applied.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

Background: Cord blood represents a link between intrauterine and early extrauterine development. Cord blood cells map an important time frame in human immune imprinting processes. It is unknown whether sex of the newborn affects the lymphocyte subpopulations in cord blood. Methods: 9 B and 21 T cell subpopulations were characterized by flow cytometry in human cord blood from 16 male and 21 female newborns, respectively. Results: Except for marginal zone B cells and transitional B cells, B cell count in all subsets was higher in cord blood of male newborns than in female newborns. Frequency of naive thymus negative Th cells was significantly higher in male cord blood whereas the remaining T cell subpopulations showed a higher count in cord blood of female newborns. Conclusion: Our study is the first revealing sex differences in B and T cell subpopulations of human cord blood. These results indicate that sex might have a higher impact for the developing immune system urging the need to expand research in this area.

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

Aims: To study the effects of pyridoxal phosphate (PLP) on oxidative stress in isolated pancreatic acinar cells. We have previously shown that PLP has cytoprotective and insulinotropic effects on mice islet cells in vivo and in vitro studies. Main methods: Acinar cells were isolated from three months old WNIN male rats and were cultured in vitro for a period of 24 h in CO₂ incubator. Later the cells were divided into four groups as untreated (group 1), H₂O₂ treatment (group 2)_, PLP treatment (group 3) and PLP followed by H₂O₂ treatment (group 4). Cell viability was confirmed using MTT assays, oxidative stress levels were measured with ROS assay, change in different protein levels were recorded by flow cytometry. The acinar cells insulin secretion assay was performed with ELISA. The amylase protein expression was assessed using confocal microscopy. Key findings: The cell viability of acinar cell in group 1 was considered as 100%, while in group 2 it was reduced to 82% due to H₂O₂ effect, and in group 3 (99.8%) and group 4 (99.5%) were near to group 1 due to the cytoprotective effect of PLP. The ROS levels were increased by 1.47 folds in group 2, while PLP decreased to 1.02 fold in group 4, which was comparable with the changes in group 1. Beneficial effects of PLP were also observed from the increased expression levels of acinar cells are amylase -2.01, neurogenin-3-9.51, PDX-1- 23.6 and insulin-13.5 in group 3 compared to group 1. The specificity of PLP’s response was confirmed by amino oxy acetic acid (AOAA), a specific PLP inhibitor. The increased amylase protein localization with PLP was confirmed by confocal microscopy. Insulin secretion efficiency of acinar cells was observed to be 6.13 folds higher at basal and 24.63 fold higher at stimulated levels in group3 compared to group1. Significance: Our results advocate the antioxidant and cytoprotective effects of PLP on the pancreatic acinar cell along with increased pancreatic marker expressions of amylase,PDX-1, neurogenin-3 and insulin proteins.

Physics-informed neural networks are a promising method to yield surrogate models of flow fields. We present a metamodeling technique for variable geometries based on physics-informed neural networks. The method was applied to the DU99W350 airfoil at a Reynolds number of 1×10⁵. The model predicted the Reynolds-averaged velocity and pressure field around the airfoil for arbitrary angles of attack between 10.0° and 17.5°. The model was trained with data from CFD simulations for a limited set of angles of attack. Additionally, satisfaction of the a priori known boundary conditions as well as the Reynolds-averaged Navier-Stokes equations were trained. A sensitivity analysis concerning the Reynolds number, the amount and distribution of training data, and the turbulence model was conducted showing the superiority of the pseudo-Reynolds stress method and the demand of labeled training data in the domain. The trained network was capable of predicting the developing flow separation on the suction surface and exhibited excellent agreement with CFD results even in the proximity to the wall for interpolations as well as extrapolations from the labeled data set.

Tropical storm Nate, which was a powerful hurricane prior to landfall along the Alabama coast, traversed north towards our instrumented site in Hunstville, AL. The rain bands lasted 18 h and the 2D-video disdrometer (2DVD) captured the event which was shallow and indicative of pure warm rain processes. Measurements of raindrop size, shape and velocity distributions are quite rare in pure warm rain and are expected to differ from cold rain processes. In particular, asymmetric shapes due to drop oscillations and their impact on polarimetric radar signatures in warm rain have not been studied so far. Recently, the 2DVD data has been used for 3D reconstruction of asymmetric raindrop shapes but their fraction (relative to the more common oblate shapes) in warm rain has yet to be ascertained. Here we compute the scattering matrix drop-by-drop using Computer Simulation Technology integral equation solver for drop sizes>2.5 mm. From the scattering matrix elements, the polarimetric radar observables are simulated by integrating over 1 minute consecutive segments of the event. These simulated values are compared with dual-polarized C-band radar data located at 15 km range from the 2DVD site to evaluate the contribution of the asymmetric drop shapes.

The adoption of harmful postures due to a sedentary lifestyle, which involves long periods at work in offices, is a factor that exacerbates musculoskeletal risks. To examine these risks, there are numerous postures analysis methods, such as Rapid Upper Limb Assessment (RULA) and Rapid Office Strain Assessment (ROSA). RULA is a consolidated method to evaluate the exposure of individual workers to ergonomic risk factors associated with upper extremity musculoskeletal disorders. In turn, ROSA is a more recent method that quantifies exposure to risk factors in an office work environment. This research aims to identify whether there is harmony between these two methods, ROSA and RULA. Through applied research, from a qualitative perspective, the scientific procedures adopted were direct observation and ROSA and RULA postural assessment instruments. The study was conducted in the radiology service and focused on the outpatient reception workstation. Results indicated that further investigation must occur to make working conditions changes as soon as possible and that both methods are harmonic. As contributions of the analysis, we have discussed the working conditions and suggested improvements to reduce the risks of musculoskeletal morbidity symptoms. We recommend future studies aimed at measuring the levels of complementarity between these methods by quantitative approaches.

This article presents raw data of biaxial tensile measurements of rat heart passive myocardium conducted in lab scale environment. The passive myocardium of the rat was divided into three regions, namely: left ventricle, mid-wall and right ventricle. The biaxial dataset of passive rat myocardia is presented as stress vs strain of the passive rat myocardium in various regions. The determination of valid material properties of the heart plays an important role in the development computational models. These computational models are useful in studying various scenarios and mechanisms of heart diseases. In addition, valid and accurate materials are critical in the development of new therapies. The dataset presented here is useful in the area of soft tissue mechanics including studying the mechanisms of heart diseases such as myocardial infarction. Accordingly, the evaluation of stress and strain in left ventricle, mid-wall and right ventricle was performed.

Cell-to-cell distant mechanical communication has been demonstrated by using in-vitro and in-vivo models. However, the molecular mechanisms underlying long-range cell mechanoresponsive interactions remain to be more elucidated. This study further examined the roles of α-Catenin and Piezo in traction force-induced rapid branch assembly of airway smooth muscle (ASM) cells on Matrigel hydrogel containing type I collagen. Our findings demonstrate that siRNA-mediated downregulation of α-Catenin or chemical inhibition of Piezo activity significantly reduced both cell directional movement and branching assembly. In regarding the role of N-cadherin in regulating branch assembly but not directional migration, our results further confirmed that siRNA downregulation of α-Catenin caused a remarked reduction of focal adhesion formation, as assessed by focal Paxillin and Integrin α5 localization. These observations implied that mechanosensitive α-Catenin was involved in both cell-cell and cell-matrix adhesions. Additionally, Piezo showed partial localization with Paxillin in focal adhesions, which was inhibited by α-Catenin downregulation with siRNA. This provides a plausible clue for Piezo mechanosensing traction force in the hydrogel. Collectively, our findings highlight the significance of α-Catenin in regulating cell-matrix interactions along with possible interpretation for Piezo mechanosensation at focal adhesions during cell-cell distant mechanical communication.

The residual multiparticle entropy (RMPE) of a fluid is defined as the difference, Δs, between the excess entropy per particle (relative to an ideal gas with the same temperature and density), s_ex, and the pair-correlation contribution, s₂. Thus, the RMPE represents the net contribution to s_ex due to spatial correlations involving three, four, or more particles. A heuristic “ordering” criterion identifies the vanishing of the RMPE as an underlying signature of an impending structural or thermodynamic transition of the system from a less ordered to a more spatially organized condition (freezing is a typical example). Regardless of this, the knowledge of the RMPE is important to assess the impact of non-pair multiparticle correlations on the entropy of the fluid. Recently, an accurate and simple proposal for the thermodynamic and structural properties of a hard-sphere fluid in fractional dimension 1 < d < 3 has been proposed [Santos, A.; López de Haro, M. Phys. Rev. E 2016, 93, 062126]. The aim of this work is to use this approach to evaluate the RMPE as a function of both d and the packing fraction ϕ. It is observed that, for any given dimensionality d, the RMPE takes negative values for small densities, reaches a negative minimum Δs_min at a packing fraction ϕ_min, and then rapidly increases, becoming positive beyond a certain packing fraction ϕ₀. Interestingly, while both ϕ_min and ϕ₀ monotonically decrease as dimensionality increases, the value of Δs_min exhibits a nonmonotonic behavior, reaching an absolute minimum at a fractional dimensionality d ≃ 2.38. A plot of the scaled RMPE Δs/|Δs_min| shows a quasiuniversal behavior in the region −0.14 ≲ ϕ − ϕ₀ ≲ 0.02.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

The excitation of the visual system increases with increasing retinal illumination. At the same time, the sensitivity of the system decreases (light adaptation). Higher excitation automatically results in a lower sensitivity. This study investigates whether this parallelism between the excitation and the sensitivity also applies in the dynamic case, that is, during the transition to a higher excitation level after an increase in the retinal illuminance. For this purpose, the courses of the subjective and the electroretinographic threshold during the transitional phase after a step of the adaptation illumination was determined by means of a special light-stimulation apparatus. As a measure of the course of the excitation during this time, the response ERG on the adaptation step was recorded with a special amplifier. The threshold curve always has an overswing, which shows subjectively very strong differences. It can be concluded that the glare caused by a sudden increase in illuminance is subjectively very different. The comparison between the response ERG on the adaptation step and the course of the electroretinographic increment threshold during this time shows a broad agreement between the two courses. It can thus be assumed that the sensitivity of the visual system follows the course of the excitation also in the dynamic case. In addition, the investigation shows that the glare experienced after a step in the illuminance clearly shows great subjective differences.

The regulation of cell death is a fundamental issue in cell biology and continues to be intensely investigated worldwide. The significance of research in this field persists because understanding the determinants of cell lifespan directly impacts the maintenance of multicellular organism homeostasis and, consequently, is crucial for addressing biomedical challenges associated with various diseases. It is recognized that the initiation of cell death can be prompted by both specific signals (such as cytokines or hormones) and nonspecific stimuli, including radiation, temperature increase, or oxidants. When these factors affect a cell, numerous signaling pathways are triggered in the cell, leading to neutralization of the effects of their negative effects or, in case of irreparable damage, to cell elimination. This removal of damaged cells occurs through apoptosis or programmed cell death, a highly regulated process. Numerous signaling molecules participate in orchestrating the apoptotic process, many of which also govern other essential functions within the organism. Physiological factors capable of triggering the apoptotic program in cells include nitric oxide (NO), which serves as one of the key signaling molecules regulating the functions of the cardiovascular, nervous, and immune systems of the organism. The unique chemical nature of NO, along with its numerous intracellular targets and physiologically active redox forms, raises questions about the specific mechanisms through which NO exerts its damaging effects on cells. Utilizing pharmacological preparations- such as sources (donors) of exogenous nitric oxide- represents an approach to investigating the initiation and execution of the apoptotic program in sensitive target cells. Furthermore, this approach holds promise as a direction for discovering new selective drugs.

The generation and maintenance of membrane potential is a fundamental part of Membrane Pump Theory. One of the key points of this hypothesis is based on a natural or facilitated molecular diffusion through several types of ion channels and pumps like the Na/K ATPase. Chemistry, physics and especially electrochemistry, however, bring strong contradictions to this theoretical assumption. By respecting the principles of chemistry and electrostatics, it becomes obvious that this theoretical hypothesis cannot work. The ionic diffusion that would be at the origin of this potential cannot take place. Indeed, the topology and the forces involved definitively exclude the current model, which must absolutely be revised according to the current state of our knowledge and allow an advance in the understanding of the phenomena and open new research perspectives.

For the past few decades, researchers have been intrigued with glassy polymers, which have applications ranging from gas separations to corrosion protection to drug delivery systems. The techniques employed to examine the sorption and diffusion of small molecules in glassy polymers are the subject of this review. Diffusion models in glassy polymers are regulated by Fickian and non-Fickian diffusion, with non-Fickian diffusion being more prevalent. The characteristics of glassy polymers are determined by sorption isotherms, and different models have been proposed in the literature to explain sorption in glassy polymers during the last few years. This review also includes the applications of glassy polymer. Despite having so many applications, current researchers still have difficulty in implementing coating challenges due to issues like as physical ageing, which is briefly discussed in the review.

Separase is a key cysteine protease to separate sister chromatids through digestion of cohesion ring that inhibits chromosome segregation as trigger of metaphase–anaphase transition in eukaryotes and highly regulated its activity by binding with securin and cyclinB-CDK1 complex. Those bindings prevent proteolytic activity of separase until the onset of anaphase. Chromosome missegregation and aneuploidy are frequently observed in malignancies. However, there are some difficulties for biochemical examinations due to instability of separase in vitro and a few spatiotemporal resolution approaches monitoring live separase activity throughout mitotic processes. Here we have developed FRET-based molecular sensors including GFP variants with separase cleavable sequences as donor and covalently attached fluorescent dye as acceptor molecules applicable to conventional live cell imaging and flow cytometric analysis because of efficient live cell uptake. We investigated performance of equivalent molecular sensors localized or not localized inside nucleus under cell cycle control using flow cytometry. Synchronized cell cycle progression rendered significant separase activity detections in both molecular sensors. We obtained consistent outcomes with localized molecular sensor introduction and cell cycle control by fluorescent microscopic observations. We thus established live cell separase activity monitoring systems specifically or statistically that could lead to elucidate separase properties in detail.

Theoretical and experimental approaches have been applied to study the polymer physics under-lying compaction of DNA in the bacterial nucleoid. Knowledge of the compaction mechanism is necessary to obtain a mechanistic understanding of the process of segregation of replicating chromosome arms (replichores) during the cell cycle. In the first part of this review light microscope observations are discussed that have demonstrated that the nucleoid has a lower refractive index and thus a lower density than the cytoplasm. A polymer-physical explanation for this phenomenon was given by the theory of Theo Odijk pro-posed in 1998. By assuming a phase separation between nucleoid and cytoplasm and by imposing equality of osmotic pressure and chemical potential between the two phases, a minimal energy situation is obtained in which soluble proteins are depleted from the nucleoid, thus explaining its lower density. The theory is compared with recent views for DNA compaction that are based on mere exclusion of polyribosomes from the nucleoid or on the transcriptional activity of the cell. These new views raise the question of whether they can still explain the lower refractive index or density of the nucleoid. In the second part of this review the question is discussed how DNA segregation occurs in Esche-richia coli, in the absence of the so-called active ParABS system, present in the majority of bacteria. How is entanglement prevented of nascent chromosome arms, generated at the origin in the pa-rental network of the E. coli nucleoid? The observations of the groups of Sherratt and Hansen in 2006, that the four nascent chromosome arms synthesized in the initial replication bubble, segre-gate to opposite halves of the sister nucleoids implies that extensive intermingling of daughter strands does not occur. Based on the hypothesis that leading and lagging replichores synthesized in the replication bubble, fold into micro-domains that do not intermingle, a passive "four-excluding-arms model" for segregation is proposed. This model implies that the key for seg-regation already lies in the structure of the replication bubble at the very start of DNA replication; it explains the different patterns of chromosome arms as well as the segregation distances between replicated loci as experimentally observed.

Circulating tumor cells (CTCs) are cells released from the primary tumor and intravasate into the blood or lymphatic vessels, where they are transported to distant sites and act as seeds that initiate cancer metastases. Recent advances in CTC research have shown their relevance as prognostic markers for early and metastatic disease detection, predictive biomarkers for relapse, and response to medical intervention or therapy. The rapidly evolving landscape of CTC biology has opened new avenues for understanding cancer progression, metastasis, and treatment response. Additionally, translating these findings into clinical applications holds promise for improving cancer diagnostics, prognosis, and personalized therapeutic strategies. This review discusses the significance of CTCs in cancer research and their associated challenges. We explore recent developments in the detection and characterization of CTCs and their implications in cancer research and clinical practice.

Multi-rotor drones, a kind of unmanned equipment which is widely used in military, commercial consumption and other fields, has been developed very rapidly in recent years. However, their short flight time has hindered the expansion of their application range. This can be addressed by utilizing hydrogen fuel cells, which exhibit high energy density, strong adaptability to ambient temperature, and no pollution emissions, as the power source. Accordingly, the application of hydrogen fuel cells as the power source in multi-rotor drones is a promising technology that has attracted significant research attention. This paper summarizes the development process of hydrogen fuel cell mul-ti-rotor drones and analyzes the key obstacles that need to be addressed for the further development of hydrogen fuel cell multi-rotor drones, including structural lightweight, hydrogen storage methods, energy management strategies. Additionally, prospects for the future development of hydrogen fuel cell multi-rotor drones are presented.

This paper investigates an innovative photovoltaic cell configuration, denoted as “Au/CuSCN/RbGeI3/CdTe/ZnO/TiO2/FTO", using SCAPS-1D simulation. The research focuses on optimizing device performance by analyzing key components, including ZnO as the electron transport layer (ETL), RbGeI3 as the perovskite absorber layer, CuSCN as the hole transport layer (HTL), and CdTe as the active buffer layer. A comparison is made with the standard “Au/CuSCN/CH3NH3SnI3/CdTe/ZnO/TiO2/FTO" configuration under dark and illuminated conditions. Through an in-depth investigation involving temperature effects, generation rate analysis, RbGeI3 absorber layer thickness, Nd level, and interface defect levels, an optimized design for a unit area is achieved. The proposed solar cell demonstrates outstanding performance metrics, including an open circuit voltage (Voc) of 0.94V, a short circuit current density (Jsc) of 34.52mA/cm2, a fill factor (FF) of 77.77%, and an energy conversion efficiency (η) of 25.40%. These values significantly outperform the reference models with energy conversion efficiencies of 10.11% and 21.09%. Real-world applicability is validated by implementing these optimized characteristics in a photovoltaic system for Pakistan’s geographical location using PVSyst software. The suggested solar cell achieves a remarkable performance ratio (PR) of 85.6%, surpassing the PR of the reference basic solar cell model at 83%. The findings of this research offer a promising and superior solar cell design, incorporating innovative materials and optimization techniques to achieve exceptional energy conversion efficiency and overall performance. This study’s outcomes have the potential to advance photovoltaic technology and contribute to sustainable energy solutions worldwide.

Based on screening in computational biology and biological in vitro assays, five natural products isolated from extracts of the herbal medicine toad skin, such as cinobufagin (CBFi), bufalin (BFi), arenobufagin (ABFi), telocinobufagin (TBFi), bufotalin (BFTi), were subjected to molecular docking calculations with the use of SARS-CoV-2 main protease (PDB 6LU7 and 7BTF) and top-scoring ligand-receptor complexes were obtained. The results showed that the binding energy of ABFi to the 3CL protein was -17.044kcal/mol, which was higher than CBFi and TBFi. However, the binding energy of ABFi to the RdRp protease was -23.250 kcal/mol, which was much lower than that of CBFi and TBFi, EVEN lower than that of ABFi to the 3CL protein. ABFi also has polar interactions with amino acids such as Glu811, Ser814, Ser681 and Thr680 of RdRp enzyme. The results revealed that ABFi had a moderate inhibitory effect on the cell proliferation of SARS-CoV-2 in vitro, with an inhibition rate of 61.12%, even weaker than Remdesivir. This new discovery provides us with new ideas for in-depth studies on the development of natural products with this class of structural generalizations as inhibitors of SARS-CoV-2, and provides an experimental basis for the next step of mechanistic studies.

The oral mucosa represents a defense between the external environment and the rest of the body and encompasses several antimicrobial and antiviral mechanisms. Oral mucosal cells are constantly bathed in hypotonic saliva (normally one-third tonicity compared to plasma) and are repeatedly exposed to environmental stresses of tonicity, temperature and pH by the drinks we imbibe (e.g. hypotonic: water, tea, coffee; hypertonic: assorted fruit juices, red wines), as well as of diverse microbial and viral flora. In the mouth, the broad-spectrum antiviral mediator MxA (a dynamin-family large GTPase) is constitutively expressed in healthy periodontal tissues, and also induced by Type III interferons (e.g. IFN-λ1). Endogenously induced human MxA and exogenously expressed human GFP-MxA formed membraneless biomolecular condensates in the cytoplasm of oral carcinoma cells (OECM1 cell line). These condensates likely represent storage granules in equilibrium with antivirally active dispersed MxA. Remarkably, cytoplasmic MxA condensates were exquisitely sensitive sensors of hypotonicity – the condensates in oral epithelium disassembled within 1-2 min of exposure of cells to saliva-like one-third hypotonicity, and spontaneously reassembled in the next 4-7 min. OECM1 cells preloaded with calcein-AM (a reporter of cytosolic “macromolecular crowding”) confirmed unquenching and then requenching of calcein fluorescence during this process. Hypertonicity had little effect on MxA condensates. The spontaneous reassembly of GFP-MxA condensates in oral epithelial cells even under continuous saliva-like hypotonicity was slowed by the protein phosphatase inhibitor cyclosporin A (CsA) and by the K-channel blocker tetraethylammonium chloride (TEA) suggestive of the involvement of the volume-sensitive WNK kinase-protein phosphatase (PTP)-K-Cl cotransporter (KCC) pathway in the regulated volume decrease (RVD) during condensate reassembly in oral cells. Thus, physiologically, hypotonic drinks (water, tea, coffee) trigger a rapid deployment of antiviral MxA throughout the cytoplasm of oral epithelial cells, with subsequent salvage of MxA back into storage granules/condensates.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

The mechanisms underlying the establishment of asymmetric structures during development remain elusive. The wing of Drosophila is asymmetric along the Anterior-Posterior (AP) axis, despite that its growth signals that drive its growth are presumably symmetric. Here, we investigated the contribution of cell recruitment, a process that drives wing fate differentiation in Drosophila, to the asymmetric shape and pattern of the adult wing. Genetic impairment of cell recruitment results in a significant reduction in adult wing asymmetry, primarily affecting the region between longitudinal vein 5 and the wing margin (L5-M). Morphometric analysis reveals that the lack of cell recruitment results in a more symmetric wing with respect to the AP, suggesting a contribution of cell recruitment to the establishment of asymmetry in the adult wing. A close examination of the expression of the wing selector gene vestigial (vg) in wing disc does not support this hypothesis. However, the circularity of the Vg pattern significantly increase in recruitment-impaired wing disc, suggesting that while the decrease of the L5-M region in the adult wing may not be attributed to cell recruitment, it could contribute to the overall asymmetry of the adult wing. We conclude that cell recruitment, a widespread mechanism that participates in growth and patterning of several developing systems, could drive, at least partially, the asymmetric shape of the Drosophila wing.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

Objective: To perform a systematic review of real-world outcomes for anti-CGRP-mAbs. Methods: Following the PRISMA guidelines, we searched PubMed for real-world data of Erenumab, Galcanezumab, Fremanezumab, or Eptinezumab in patients with migraine. Results: We identified 104 publications (73 retrospective), comprising 8 pharmaco-epidemiologic and 63 clinic-based studies, 30 case reports and 3 other articles. None of the clinic-based studies provided follow-up data over more than one year in more than 200 patients. Findings suggest reductions in health insurance claims and days with sick-leave as well as better treatment adherence with anti-CGRP-mAbss. Effectiveness, reported in 59 clinic-based studies, was comparable to randomized controlled trials. A treatment pause was associated with an increase in migraine frequency and switching to another antibody resulted in a better response in some of the patients. Adverse events and safety issues were addressed in 70 papers including 22 single case reports. Conclusion: Real-world data on anti-CGRP-mAbs are limited by retrospective data collection, small patient numbers and short follow-up periods. The majority of papers seem to support good effectiveness and tolerability of anti-CGRP-mAbs in the real-world setting. There is an unmet need for large prospective real-world studies providing long-term follow-up of patients treated with anti-CGRP-mAbs.

Short-term (hours) biological and biogeochemical processes cannot be fully captured by the current suite of polar-orbiting satellite ocean color sensors, as their temporal resolution is limited to potentially one clear image per day. Geostationary sensors, such as the Geostationary Ocean Color Imager (GOCI) from the Republic of Korea, allow the study of these short-term processes because their geostationary orbits permit the collection of multiple images throughout each day. To assess the capability to detect changes in water properties caused by these processes, however, requires an understaning of the uncertainties introduced by the instrument and/or geophysical retrieval algorithms. This work presents a study of the variability during the day over a water region of low-productivity with the assumption that only small changes in the water properties occur during the day over the area of study. The complete GOCI mission data were processed using the SeaDAS/l2gen package. Filtering criteria were applied to assure the quality of the data. Relative differences with respect to the midday value were calculated for each hourly observation of the day. Also, the influence of the solar zenith angle in the retrieval of remote sensing reflectances and derived products was analyzed. We determined that the uncertainties in water-leaving “remote-sensing” reflectance ($R_\text{rs}$) for the 412, 443, 490, 555, 660 and 680 nm bands on GOCI are 8.05$\times10^{-4}$, 5.49$\times10^{-4}$, 4.48$\times10^{-4}$, 2.51$\times10^{-4}$, 8.83$\times10^{-5}$, and 1.36$\times10^{-4}$ sr$^{-1}$, respectively, and 1.09$\times10^{-2}$ mg m$^{-3}$ for the chlorophyll-a concentration (Chl-{\it a}), 2.09$\times10^{-3}$ m$^{-1}$ for the absorption coefficient of chromophoric dissolved organic matter at 412 nm ($a_{\text{g}}(412)$), and 3.7 mg m$^{-3}$ for particulate organic carbon (POC). We consider these to be the floor values for detectable changes in the water properties due to biological, physical or chemical processes.

The diffusion coefficient (D) is a key parameter characterizing gas transport in coal seams. Usually, the D is calculated from the desorption curve of particle coal, which cannot accurately reflect the diffusion characteristics under the stress constraint conditions of in-situ coal seams. In this paper, based on Fick's law of counter diffusion, different metamorphic deformed coals of medium and high coal rank are taken as the research object. The change laws of D under different confining pressure, gas pressure, and temperature conditions are tested and analyzed, and the influencing mechanisms on the D are discussed. The results show that the D of different metamorphic deformed coals decreases exponentially with the increase of confining pressure, and increases exponentially with the increase of gas pressure and temperature. There is a limit diffusion coefficient. The influence of confining pressure on the D is essentially determined by the change of effective stress, and the D has a negative effect of effective stress similar to permeability. The effect of gas pressure on the D involves two mechanisms, namely, mechanical and adsorption effects, which are jointly restricted by effective stress and coal particle shrinkage and expansion deformation. The effect of temperature on the D is mainly achieved by changing the root mean square speed and average free path of gas molecules. Under the same temperature and pressure conditions, the D increases first and then decreases with the increase of deformation degree, and the D of fragmented coal is the largest. Under similar deformation conditions, the D of high-rank anthracite is greater than that of medium-rank fat coal. It is considered that porosity is the key factor affecting the change of D in different metamorphic deformed coals.

An interesting anomaly of the diffusion process with an apparently negative diffusion coefficient defined through the mean-square displacement in a one-dimensional quantum molecular chain model is shown. Nevertheless, the system satisfies the H-theorem, so that the second law of thermodynamics is satisfied. The reason why the “diffusion constant” becomes negative is due to the effect of the phase mixing process, which is a characteristic result of the one-dimensionality of the system. We illustrate the situation where this negative “diffusion constant” appears.

African swine fever (ASF) is a viral infection of pigs and represents a major threat to animal health and trade. Due to the high tenacity of the causative virus also in carcasses of wild boar, contacts of wild boar with infectious carcasses are regarded an important driver of the so-called habitat cycle. The latter is believed to play a major role in maintaining the present ASF situation in wild boar in Europe. Therefore, search campaigns and timely removal and disposal of carcasses are considered important disease control approaches. If timely disposal is not feasible due to logistic reasons, deterrence of wild boar could be a provisionary option. The performance of seven deterrents (physical and chemical) was tested in a forest near Greifswald, Germany. Carcasses as entities of attraction for wild boar were substituted by luring sites. It could be demonstrated that certain physical (LED-Blinkers, aluminum stripes) and chemical (Wildschwein-Stopp™, Hukinol™) deterrents are capable of reducing significantly the odds of wild boar contacts to one third. It is recommended to carry a choice of the aforementioned, reasonable and easy to apply deterrents, when carcass search campaigns are launched in case of an outbreak of ASF in wild boar.

Diffusion bonding is often used on pre-machined parts to generate internal cavities, e.g. for cooling injection molding tools close to the mold cavity. Only then, the workpieces are finished to their final dimensions. In the case of micro-process devices, however, it is essential to precisely control the deformation, as otherwise uncontrollable pressure losses will occur with channel cross-sections in the sub-millimeter range. Post-processing is not possible. The most important process parameters for diffusion bonding are temperature, dwell time and contact pressure, with the bonding temperature and contact pressure acting in opposite directions and showing a strong non-linear dependence on deformation. In addition, the deformation is influenced by a number of other factors such as the absolute size of the cross-section and the aspect ratio of the parts, the dimensions and distribution of the internal cross sections and the overall percentage of the cross-section to be bonded. In micro process engineering, small material cross-sections in the range of the materials microstructure can facilitate additional deformation mechanisms such as grain boundary sliding, which are not relevant at all for larger structures. For parts consisting of multiple layers, tolerances in thickness and roughness of multiple surfaces must be levelled, contributing to the percentaged deformation. This makes it difficult, especially in micro process engineering and in single or small series production, to determine suitable joining parameters in advance, which on the one hand do not cause unforeseen large deformations, but on the other hand reliably produce highly vacuum-tight components. Hence, a definition of a fixed percentaged deformation does not work for all kinds of components. This makes it difficult to specify parameters for surely obtain high-vacuum tight parts. For successful diffusion bonding, atoms must diffuse over the bonding planes, forming a monolithic part in which the original layers are no longer visible. Only then, mechanical properties identical to those of the base material, which has been subjected to identical heat treatment, can be achieved. In this paper, the impacts of different material cross section widths as well as of the aspect ratio on deformation were investigated. By accident, it was found that also accuracy of the temperature measurement may have a serious impact in terms of deformation.

It is shown by numerical modelling that anisotropic diffusion can compensate and even overcome diffusion broadening - the main limiting factor of devices working at atmospheric pressure. The thickness of ion clouds coming out of the ionisation chamber is reduced ~ 1000 times in the ADMA inlet increasing the resolution. This finding has a great potential that enables construction of a device with resolution close to that of currently available desktop ion separation devices – high pressure mass spectrometers, but with much lower cost of manufacture and with smaller dimensions. Comprehensive numerical modelling along with mathematical analysis of physical concepts enables reduction of the footprint and manufacturing costs. Modelling determined that the resolving power (RP) potential of the ADMA is greater than the RP of currently available on the market devices for the airport security market. The ADMA technology enables very fast detection of threats; at least 100 times faster than currently used in Ion Mobility Spectrometers (IMS). This potentially allows an increase in passenger throughput in airports.

A set of programs for the numerical simulation of the diffusion decomposition processes was developed by using simulation methods, kinetic and particle method. The complex has been validated on the model system Ni-Al by the growth of -phase separations. The results on the evolution of the distribution function and other characteristics of the ensemble, which in the zero volume fraction approximation are asymptotically in good agreement with the theory and the experiment, have been obtained. The peculiarity of the created program complex is the possibility of its adaptation to the description of the decomposition of multicomponent multiphase systems. Fig. 6, list of references - 19 titles.

This article is devoted to Feller's diffusion equation which arises naturally in probabilities and physics (e.g. wave turbulence theory). If discretized naively, this equation may represent serious numerical difficulties since the diffusion coefficient is practically unbounded and most of its solutions are weakly divergent at the origin. In order to overcome these difficulties we reformulate this equation using some ideas from the Lagrangian fluid mechanics. This allows us to obtain a numerical scheme with a rather generous stability condition. Finally, the algorithm admits an elegant implementation and the corresponding Matlab code is provided with this article under an open source license.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

Addressing the pressing challenge of global warming, reducing greenhouse gas emissions in the transportation sector is a critical imperative. Battery and fuel-cell electric vehicles have emerged as promising solutions for curbing emissions in this sector. In this study, we conducted a comprehensive life cycle assessment (LCA) for typical passenger vehicles, heavy duty trucks and city buses using either proton-exchange membrane fuel cells or Li-ion batteries with different cell chemistries. To ensure accuracy, we supplemented existing studies with data from the literature, particularly for the recycling phase, as database limitations were encountered. Our results highlight that fuel cell and battery systems exhibit large emissions in the production phase. Recycling can significantly offset some of these emissions, but a comparison of the technologies examined revealed considerable differences. Overall, battery electric vehicles consistently outperform fuel cell electric vehicles regarding absolute greenhouse gas emissions. Hence, we recommend prioritizing battery electric over fuel cell vehicles. However, deploying fuel cell electric vehicles could become attractive in a hydrogen economy scenario where other factors, e. g. the conversion and storage of surplus renewable electricity via electrolysis, become important.

Studies on the possible association between bacteria and oral squamous cell carcinoma (OSCC) remain inconclusive, largely due to methodological variations/limitations. The objective of this study was to characterize the species composition as well as functional attributes of the bacteriome associated with OSCC. DNA obtained from 20 fresh OSCC biopsies (cases) and 20 deep-epithelium swabs (matched control subjects) were sequenced for the V1-V3 region using Illumina’s 2x300 bp chemistry. High quality, non-chimeric merged reads were classified to species level using a prioritized BLASTN-algorithm. Downstream analyses were performed using QIIME, PICRUSt, and LEfSe. Fusobacterium nucleatum subsp. polymorphum was the most significantly overrepresented species in the tumors followed by Pseudomonas aeruginosa and Campylobacter sp. Oral taxon 44, while Streptococcus mitis, Rothia mucilaginosa and Haemophilus parainfluenzae were the most significantly abundant in the controls. Functionally, genes involved in bacterial mobility, flagellar assembly, bacterial chemotaxis and LPS synthesis were enriched in the tumors while those responsible for DNA repair and combination, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, ribosome biogenesis and glycolysis/gluconeogenesis were significantly associated with the controls. This is the first epidemiological evidence for association of F. nucleatum and P. aeruginosa with OSCC. Functionally, an “inflammatory bacteriome” is enriched in OSSC.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Growing interest has accrued in the co-existence of cardiac amyloidosis and valvular heart disease. Amyloid infiltration from either transthyretin (ATTR) or light chain (AL) origin may affect any structure of the heart, including the valves. Recent literature has mainly focused on aortic stenosis and cardiac amyloidosis, improving our understanding of epidemiology, diagnosis, treatment and prognosis of this dual pathology. Even though of high clinical relevance, data on mitral/tricuspid regurgitation and cardiac amyloidosis is rather scarce and mostly limited to case reports and small cases series. It is the aim of this review article to summarize the current evidence of concomitant valvular heart disease and cardiac amyloidosis including epidemiology, diagnostic approaches, screening possibilities, therapeutic management, and prognostic implications.

Naturally fermented dairy products are an important component of the human diet. They are a valuable source of nutrients as well as vitamins and minerals. Their importance as a source of probiotic bacterial strains should not be overlooked. A number of studies highlights the positive effects of species of the Lactobacillacea on the intestinal microbiota, the overall homeostasis of the body, as well as a complementary treatment for some diseases. However, data on the effects on intestinal epithelial cells of postmetabolites released by bacteria are incomplete. This is likely due to the fact that these effects are species and strain specific. In the present study, we investigated the effects of postmetabolites produced by a pre-selected candidate probiotic strain Limosilactobacillus fermentum on HT-29 intestinal epithelial cells. Our data showed a pronounced proliferative effect, evaluated by flow cytometry, quantification of cell population, and determination of mitotic index. This was accompanied by stabilization of the cell monolayer, measured by increase of TEER (trans epithelial electric resistance) and reorganization of actin filaments. The data obtained are a clear indication of the positive effects, that the products secreted by L. fermentum strain 53 have on the intestinal epithelial cells.

Our results demonstrated that SWT stimulates osteoblastogenesis and increase the cell number of osteoblasts, suggesting positive regulatory effects on osteoblast differentiation. However, the effect of SWT on bone formation need further examination, since the expression of alp gene is downregulated. On the other hand, SWT appears to negatively regulate osteoclast differentiation and bone resorption, as number of osteoclasts and the expression of critical bone resorptive genes are all downregulated. Collectively, SWT might change the equilibrium of bone remodeling and increase the bone mass. Our data provided supportive evidences that this medicine formulation can be applied to treat osteoporosis or bone destructive diseases.

Visceral leishmaniasis is a disease caused by protozoa of the species Leishmania (Leishmania) infantum (syn=Leishmania chagasi) and Leishmania (Leishmania) donovani, which are transmitted by hematophagous in-sects of the genera Lutzomyia and Phlebotomus. The domestic dog (Canis familiaris) is considered the main ur-ban reservoir of the parasite due to the high parasite load on its skin, serving as a source of infection for sand-fly vectors and, consequently, perpetuating the disease in the urban environment. Some factors are consid-ered important in the perpetuation and spread of canine visceral leishmaniasis (CVL) in urban areas, such as stray dogs with their errant behavior and houses that have backyards with trees, shade, and organic materi-als, creating an attractive environment for sandfly vectors. CVL is found in approximately 50 countries with the number of infected dogs reaching millions and, due to the difficulty of controlling and diagnosing the disease, the number of infected animals could be even greater. In the four continents endemic for CVL there are reports of disease expansion in endemic countries such as Brazil, Italy, Morocco, and Tunisia, as well as in areas where CVL is not endemic, for example, Uruguay. Socio-environmental factors, such as migration, drought, deforestation, and global warming, have been pointed out as one of the reasons for expansion to ar-eas where it had been absent. Thus, the objective of this review is to address (i) the distribution of CVL in endemic areas (ii) the role of the dog in the visceral leishmaniasis epidemiology and the factors that influence dog infection and spread of the disease, and (iii) the challenges faced in the control of CVL.

Background: Metastatic tumors to the oro-facial tissues are rare, with an incidence ranging between 1% and 8% of all oral malignant tumors. Generally reported with a peak of incidence in the 5th–7th decades, but possibly occurring at any age, metastases may represent the first sign of an occult cancer or manifest in patient with an already known history of a primary carcinoma, mostly from the lungs, kidney, prostate, and colon-rectum in males, or uterus, breast, lung, and ovary in females. In the oro-facial tissues the sites mostly involved are the oral mucosa, gingiva/jawbones, tongue, and the salivary glands. Methods: A systemic Review of the literature on the oro-facial metastases from Renal Cell Carcinoma has been conducted by searching the most used databases, also focusing the attention on the Clear Cell histological variant, representing the most frequent one. Results: Among the 160 analyzed studies, 211 cases of oral metastases of renal cancer were found (148 in males, 70.1%; 63 in females, 29.8%), with an average age of 59.8 years. In almost 40% of cases, metastasis represented the first clinical manifestation of the primary tumor and 122 were histologically diagnosed as ccRCCs (57.8%). The tongue was involved in most of the cases (26% - 55 cases), followed by mandible (18.9% - 40 cases), gingiva (18.4% - 39 cases), maxilla (10.9% - 23 cases), parotid gland (10.4% - 22 cases), buccal mucosa (5.2% - 11 cases), lips (3.3% - 7 cases), hard palate (2.8% - 6 cases), soft palate, masticatory space and submandibular gland (0.9% - 2 cases), lymph nodes, tonsil and oral floor (0.4% - 1 case). Among the 122 ccRCCs (84 were males, 68.8 %; 38 females, 31.1%), with an average age of 60.8 years and representing in 33.6% the first clinical manifestation, the tongue remained the most involved site (25.4% - 31 cases), followed by the gingiva (17.2% - 21 cases), parotid gland (13,1% - 16 cases), mandibular bone (12.2% - 15 cases), maxillary bone (11.4% - 14 cases), buccal mucosa and lips (4.9% - 6 cases), hard palate (4% - 5 cases), submandibular gland and soft palate (1.6% - 2 cases), lymph nodes, tonsil, oral floor and masticatory space (0.8%. 1 case). The clinical presentation in soft tissues was represented by a fast-growing exophytic mass, sometimes accompanied by pain. Instead inn bone appeared as radiolucent lesions, with ill-defined borders and cortical erosion. Conclusions: Our data focus the attention on the incidence of Renal cancer Metastases in the oro-facial tissues. Their early identification surely represents a diagnostic challenge, especially when the clinical work-up is limited to the cervico-facial region. Nevertheless, early diagnosis and recently introduced adjuvant therapies may represent the key for better outcomes. Therefore, general guidelines about clinical and radiological identification of oro-facial potentially malignant lesions should be part of the cultural background of any dentists.

For the first time, the effect of a significant change in the resistance of the aquatic environment of a population of protozoan microorganisms under the influence of radiofrequency electromagnetic radiation from cell phones has been experimentally studied. The results of the experiment demonstrate the biological nature of the changes occurring in the “water population of protozoa” system, which indicates that the impact of radiation directly affects the cell. This conclusion is confirmed by the same order of magnitude time of information exchange between individual individuals of the population in the calculation and in the experiment. An extremely low concentration of protozoa in the experiment was established, equal to 1000 pcs./liter, at which the indicated effect is observed.An unambiguous dependence of the biological effect in the “water – amoeba population” system on the average power of electromagnetic radiation of cell phones, both in standby mode and in talk mode, has been established. It is concluded that the presented method of changing the physical properties of the aquatic environment of a population of protozoa under the influence of electromagnetic fields can be a model experiment in identifying the mechanisms of interaction of biological systems with electromagnetic radiation, determining the response time of biological systems to external electromagnetic influence, and establishing the degree of influence of radiation in the 4G, 5G ranges.

Tinnitus is a complex and heterogeneous psycho-physiological disorder responsible for causing a phantom ringing or buzzing sound albeit the absence of an external sound source. It has a direct influence on affecting the quality of life of its sufferers. Despite being around for a while, there hasn’t been a cure for tinnitus, and the usual course of action for its treatment involves use of tinnitus retaining and sound therapy, or Cognitive Behavioral Therapy (CBT). One positive aspect about these therapies is that they can be administered face-to-face as well as delivered via internet or smartphone. Smartphones are especially helpful as they are highly personalized devices, and offer a well-established ecosystem of apps, accessible via respective marketplaces of differing mobile platforms. Note that current therapeutic treatments such as CBT have shown to be effective in suppressing the tinnitus symptoms when administered face-to-face, their effectiveness when being delivered using smartphones is not known so far. A quick search on the prominent market places of popular mobile platforms (Android and iOS) yielded roughly 250 smartphone apps offering tinnitus-related therapies and tinnitus management. As this number is expected to steadily increase due to high interest in smartphone app development, a contemporary review of such apps is crucial. In this paper, we aim to review scientific studies validating the smartphone apps, particularly to test their effectiveness in tinnitus management and treatment. We use the PRISMA guidelines for systematic identification of studies on major scientific literature sources and delineate the outcomes of identified studies.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2,500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72h of cultivation. The analysis of mean PI showed significant differences between 45,X and 46,XN lineages; however there were no intraindividual differences. On the other hand, mean SCE frequencies showed no differences between the two lineages, but there were intraindividual differences in 5 patients. The absence of mean SCE frequency differences between 45,X and 46,XN lineages may indicate that both were equally unstable, as more than 70% of the 46,XN lineages had an anomalous karyotype. However, 46,XN had a higher mean PI, suggesting that the amount of cells with a karyotype distinct from 45,X may increase with time in mosaic TS women.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

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

An algorithm for the treatment of images affected by both blurring and salt&pepper noise is proposed with a cost only proportional to the number of pixels. The methodology uses a discretization scheme for the Laplace operator multiplied by a suitable nonlinear term depending on the gradient. Even if this approach resembles a diffusion type algorithm, only one step of the procedure is applied, leading to significant time savings. The procedure is successfully tested on some standard black&white natural images.

Pulsed-field gradient (PFG) diffusion experiments can be used to measure anomalous diffusion in many polymer or biological systems. However, it is still complicated to analyze PFG anomalous diffusion, particularly the finite gradient pulse width (FGPW) effect. In practical applications, the FGPW effect may not be neglected such as in clinical diffusion magnetic resonance imaging (MRI). Here, two significantly different methods are proposed to analyze PFG anomalous diffusion: the effective phase shift diffusion equation (EPSDE) method and an observing the signal intensity at the origin method. The EPSDE method describes the phase evolution in virtual phase space, while the method to observe the signal intensity at the origin describes the magnetization evolution in real space. However, these two approaches give the same general PFG signal attenuation including FGPW effect, which can be numerically evaluated by a direct integration method. The direct integration method is fast and without overflow. It is a convenient numerical evaluation method for Mittag-Leffler function type PFG signal attenuation. The methods here provide a clear view of spin evolution under field gradient, and their results will help the analysis of PFG anomalous diffusion.

Enormous quantities of softwood and hardwood tree bark are generated yearly in the pulp and woodworking industry. Chemical compounds which can be found in bark extracts have important biological properties and therefore a high potential for using in the production of special formulations. In the present study, extraction of Picea abies bark with organosolv solvents was investigated to achieve a high yield of desirable compounds. For the extraction four different solvent ratios of ethanol and water were applied. The temperature range of extraction was set between 40 and 100 °C and stirring velocity of 400 rpm. Extractions were performed with a solid/liquid ratio of 1:20. Yields of phenolics, flavonoids and tannins were determined using gallic acid for total phenolic content (TPC), quercetin for total flavonoid content (TFC) and tannic acid for total tannins content (TTC) as calibration compounds. Qualitative analysis of phenolic constituents was performed after their derivatization, by gas chromatography coupled with mass spectrometry identification. The total yield of bark extract of 14.75 wt.% was achieved by using an ethanol/water ratio of 50% (v/v) and a temperature of 100 °C. Gas chromatography results show 9 aromatic carboxylic acids as phenolic acids and quercetin and (+)-catechin as flavonoid compounds. Highest concentrations of TPC = 3.21 mg gallic acid equivalent/g, TCF = 0.62 mg quercetin equivalent/g and TTC = 0.84 tannic acid equivalent/g were determined at the same process conditions by photometric method. This study determined the conditions for organosolv extraction of useful compounds and suggests that some of extractives, e.g., taxifolin and rhamnetin presented in the spruce bark extracts, have antiviral (SARS-CoV-2) effects. Therefore, this warrants further evaluation of the antiviral properties of spruce bark constituents.

: Oscillation synchronization through diffusion-based communication of active materials can lead to emergence of diverse patterns and collective behaviors. A detailed general description of the formation process of synchronization or resynchronization dynamics is a challenging task. We employ a photosensitive Belousov-Zhabotinsky reaction-diffusion model (within a gel media) to investigate the recovery process of oscillation synchronization between a pair of gel patches. The recovery time for oscillation resynchronization can be modulated by patch-distance, species of signaling molecules, intensity and duration of illumination. Analysis reveals that the “switch effect” of the gel-distance and the “promotion effect” from illumination on the oscillation resynchronization originate from the competition between processes of photo-promotion of oscillation, diffusion of signaling molecules (HBrO2 and Br-) and disproportionation of HBrO2. These results will benefit studies on bio-inspired active materials and soft motors.

The focus of this paper is on analyzing the role and the choice of parameters in sociophysics diffusion models, by leveraging the potentialities of sociophysics from a mathematical programming perspective. We first present a generalised version of Galam’s opinion diffusion model (see, e.g. , ). For a given selection of the coefficients in our model, this proposal yields the original Galam’s model. The generalised model suggests guidelines for possible alternative selection of its parameters that allow to foster diffusion. Examples of the parameters selection process as steered by numerical optimisation, taking into account various objectives, are provided.

Dynamics of human populations can be affected by various socio-economic factors through their influence on the natality and mortality rates, and on the migration intensity and directions. In this work we study an economic-demographic model which takes into account the dependence of the wealth production rate on the available resources. In the case of nonlocal consumption of resources the homogeneous in space wealth-population distribution is replaced by a periodic in space distribution for which the total wealth increases. For the global consumption of resources, if the wealth redistribution is small enough, then the homogeneous distribution is replaced by a heterogeneous one with a single wealth accumulation center. Thus, economic and demographic characteristics of nonlocal and global economies can be quite different in comparison with the local economy.

Master equations define the dynamics that govern the time evolution of various physical processes on lattices. In the continuum limit, master equations lead to Fokker-Planck partial differential equations that represent the dynamics of physical systems in continuous spaces. Over the last few decades, nonlinear Fokker-Planck equations have become very popular in condensed matter physics and in statistical physics. Numerical solutions of these equations require the use of discretization schemes. However, the discrete evolution equation obtained by the discretization of a Fokker-Planck partial differential equation depends on the specific discretization scheme. In general, the discretized form is different from the master equation that has generated the respective Fokker-Planck equation in the continuum limit. Therefore, the knowledge of the master equation associated with a given Fokker-Planck equation is extremely important for the correct numerical integration of the latter, since it provides a unique, physically motivated discretization scheme. This paper shows that the Kinetic Interaction Principle (KIP) that governs the particle kinetics of many body systems, introduced in [G. Kaniadakis, Physica A 296, 405 (2001)], univocally defines a very simple master equation that in the continuum limit yields the nonlinear Fokker-Planck equation in its most general form.

Almost all modern inorganic light-emitting diode (LED) designs are based on double heterojunctions (DHJs) whose structure and current injection principle have remained essentially unchanged for decades. Although highly efficient devices based on the DHJ design have been developed and commercialized for energy-efficient general lighting, the conventional DHJ design requires burying the active region (AR) inside a pn-junction. This has hindered the development of emitters utilizing nanostructured ARs located close to device surfaces such as nanowires or surface quantum wells. Modern DHJ III-N LEDs also exhibit resistive losses which arise from the DHJ device geometry. The recently introduced diffusion-driven charge transport (DDCT) emitter design offers a novel way to transport charge carriers to unconventionally placed ARs. In a DDCT device, the AR is located apart from the pn-junction and the charge carriers are injected into the AR by bipolar diffusion. This device design allows the integration of surface ARs to semiconductor LEDs and offers a promising method to reduce resistive losses in high power devices. In this work, we present a review of the recent progress in gallium nitride (GaN) based DDCT devices, and an outlook of potential DDCT has for opto- and microelectronics.

Here, we present a staged approach for an innovative repurposing of a portable infant humidicrib into a live cell growth, observation, and imaging system. Furthmore, humidicrib can support different variations of “umbilical” bioreactors, and can be used to conduct electrophysiology experiments and in situ immunohistochemistry. Modifications incorporate a closed loop carbon dioxide (CO₂) concentration control system with umbilical CO₂ and heating support for tailored bioreactors. The repurposing cost is inexpensive and allows for the continued observation and imaging of cells. This prototype unit has been used to continuously observe and image live primary neurons for up to 21 days. This demonstrates the repurposed units’ suitability for use in tissue culture based research, particularly where modifications to microscopes are required or where sensitive manipulation outside of a standard incubator is needed.

This study aimed to evaluate the impact of Candida albicans on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between control and test conditions. The biofilm developed with C. albicans at 72 h had a higher bacterial biomass, with a significantly higher cell viability (p &lt; 0.05). After both 48 and 72 h of incubation, in the presence of C. albicans, there was a significant increase in counts of Fusobacterium nucleatum and Porphyromonas gingivalis and in the cell viability of Streptococcus oralis, Aggregatibacter actinomycetemcomitans, F. nucleatum, and P. gingivalis. Using a dynamic in vitro multispecies biofilm model, C. albicans exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.

Glioblastoma (GBM) still presents as one of the most aggressive tumors in the brain, which despite enormous research efforts remains incurable until today. As many theories evolve around the persistent recurrence of this malignancy the assumption of a small population of cells with a stem-like phenotype remains as a key driver of its infiltrative nature. In this article we research Chordin-like 1 (CHRDL1), a secreted protein, as a potential key regulator of the glioma stem-like cell (GSC) phenotype. It has been shown that CHRDL1 antagonizes the function of Bone Morphogenic Protein 4 (BMP4), which induces GSC differentiation and hence reduces tumorigenicity. We therefore employed two previously described GSCs spheroid cultures and depleted them of CHRDL1 using stable transduction of a CHRDL1-targeting shRNA. We show with in vitro cell based assays (MTT, limiting dilution and sphere formation assays), western blots, irradiation procedures and quantitative real-time PCR that depletion of the secreted BMP4 antagonist CHRDL1 prominently decreases functional and molecular stemness traits resulting in enhanced radiation sensitivity. As a result, we postulate CHRDL1 as an enforcer of stemness in GSCs and find additional evidence that high CHRDL1-expression might also serve as a marker protein to determine BMP4-susceptibility.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Functional genomics, a multidisciplinary subject, investigates the functions of genes and their products in biological systems to better understand diseases and find new drugs. Drug repurposing is an economically efficient approach that entails discovering novel therapeutic applications for already-available medications. Genomics enables the identification of illness and therapeutic molecular characteristics and interactions, which in turn facilitates the process of drug repurposing. Techniques like gene expression profiling and Mendelian randomization are helpful in identifying possible medication candidates. Progress in computer science allows for the investigation and modelling of gene expression networks that involve large amounts of data. The integration of data from DNA, RNA, and protein activities has resemblance to pharmacogenomics, which is of utmost importance in the development of cancer drugs. Functional genomics in drug discovery, particularly for cancer, is still not thoroughly investigated, despite the existence of a significant amount of literature on the subject. Next-generation sequencing and proteomics present highly intriguing opportunities. Publicly available databases and mining techniques facilitate the development of cancer treatments based on functional genomics. Expanding the study and application of functional genomics has great promise to advance the process of discovering and repurposing drugs, especially in the field of oncology.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

A harmful impact of climate change and global warming has concerned various sectors of the international community. Numerous energy policies aiming at climate change mitigation have been implemented on a national and global scale. Renewable Energy Technologies (RET) play a critical role in enhancing sustainable solutions that significantly limit greenhouse gases (GHG) emissions. Such innovative technologies can facilitate energy transition through providing e.g. energy security, sustainable development, or effective usage of indigenous resources. However, the commercialization of RET becomes extremely challenging. The barriers can be of a different nature, although in this study the focus has been put on socio-economic and regulatory issues. In fact, there is ample evidence that energy policies play a central role in supporting renewables adoption. It is also claimed that RET require the whole ecosystem to support their successful diffusion. In this study, we explore multifarious barriers for a widespread RET diffusion in two European Union countries: Finland and Poland, indicating the most common barriers existing in the literature as well as analyzing major bottlenecks in the viewpoint of renewable energy companies’ executives. We also present statistics of the most commonly used RET in these countries in order to express the diffusion issues more appropriately. The outcomes of this study provide useful insight for the researchers in the energy transition field as well as practical managerial and regulatory implications aimed at overcoming these challenges.

A number of experiments suggest that the elementary particles are non-local entities. A dissipative self-organization, that treats particles as open systems may provide a better understanding of the underlying phenomena than conservative models. The proposed toy model is such an attempt. We found that self-gravitation (although accompanied by self-diffusion) may not only be compatible with the quantum phenomena but is perhaps the major reason for the existence of quantum fields. According to the proposed model, fields/particles (resemble those of the Standard Model) emerge from a dynamic self-organized medium (which we associate with vacuum dust) from competition between self-gravitation and self-diffusion. These forces produce turbulence in the form of vortices (which we call vacuum cells) that serve as the building blocks for fields and particles. Field/particle features and symmetries are based on their internal (intracellular) dynamics and vortex synchronization (intercellular dynamics). This model allows for rough estimations of relative field coupling strengths, the quantity of charges and flavors, the probabilities of quark transmutations, the dimensionality and the topologies of phase spaces, and other Standard Model parameters that came not from the theory but rather determined by experiment.

Heart myocardia are critical to the facilitation of heart pumping and blood circulating around the body. The biaxial mechanical testing of the Left Ventricle (RV) is utilised to build the computa-tional model of the whole heart with little importance given to the unique mechanical properties of Right Ventricle (RV) and Mid-wall (MDW). Most of those studies focussed on the LV of the heart, and then apply the obtained characteristics with a few modifications to the right side of the heart. However, that view has been contested over time with the realisation that the right side of the heart possesses its own unique mechanical properties that are widely distinct from that of the left side of the heart. This paper is aimed at reporting and evaluating the passive mechanical property dif-ferences in the three main walls of the rat heart based on biaxial tensile test data. Fifteen mature Wistar rats weighing 225 ± 25 g were euthanised by inhalation of 5 % halothane. The hearts were excised after which all the top chambers comprising the two atria, pulmonary and vena cava trunks, aorta and valves are all dissected out. Then 5 x 5 mm sections from the middle of each wall were carefully dissected with a surgical knife to avoid over-prestraining the specimens. The specimens were subjected tensile test. The elastic moduli, peak stresses in the toe region and stresses at 40 % strain, anisotropy indices as well as the stored strain energy in the toe and linear region up to 40 % strain are used for statistical significance tests. The following are the main findings of this study: (1) LV and MDW tissues have relatively shorter toe regions of 10 - 15 % strain as compared to RV tissue whose toe region extends up to twice as much as that (2) LV tissues have higher strain energy storage in the linear region despite being lower in stiffness than the RV (3) the MDW has the highest strain energy storage along both directions which might be directly related to its high level of anisotropy. These findings, though for a specific animal species at similar age and around the same body mass, emphasize the importance of application of wall specific material parameters to obtain accurate ventricular hyperelastic models. The findings further enhance our understanding of the desired mechanical behaviour of the different ventricle walls.

Antler is the fastest growing tissue. Because is based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus its extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound testing direct effects in cells of different tumours: glioblastoma (GBM), colorectal and breast cancer, and leukaemia. DVA reduced viability of tumour but not healthy cells. Mobility decreased at least at the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight 66.3% and 61.4% respectively, and also spleen weight. In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related with tumour fighting and down-regulated those related with inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system.

5-(4-aminophenyl )-2-amino -1,3,4-thiadiazole was prepared by reaction of Thiosemicarbazide with 4-amino benzoic acid under reflux condition for 7 hours. The compound which has been synthesized successfully was subjected to addition reaction with 4-(Dimethylamino) benzaldehyde under reflux condition for 6 hours to synthesize Schiff bases. These compounds was characterized by using FTIR) and evaluated for their anticancer activity. The effect of (1, 3, 4-thiadiazole derivative) on the activity of malignant cells was studied by using different types of cell lines [Breast cancer, and human prostate cancer]. And was used the Electron microscope to show that the effect of the derivative on the cancer cells before and after 3 days of the injection time. It was found that the Schiff base of thiadiazole-1,3,4-(Dimethylamino)benzylidineamino]- [4-2-phenyl]amino was effective in reducing the size and density of malignant cells. That of 46.7 while in breast ) 145(DUprostate for growth inhibition produce of equal 85.9 µg/ml.

This paper constituted an extension of two previous studies concerning the mathematical development of the grain boundary grooving in polycrystalline thins films in the cases of the evaporation/condensation and diffusion taken separately. The thermal grooving processes are deeply controlled by the various mass transfer mechanisms of evaporation–condensation, surface diffusion, lattice diffusion, and grain boundary diffusion. This study proposed a new original analytical solution to the mathematical problem governing the grain groove profile in the case of simultaneous effects of evaporation-condensation and diffusion in polycrystalline thin films submitted to thermal and mechanical stress, and fatigue effects; by resolving the corresponding fourth-order partial differential equation ∂y∂t=C∂2y∂x2-B∂4y∂x4 obtained from the approximation y'2≪1. The comparison of the new solution to that of diffusion alone proved an important effect of the coupling of evaporation and diffusion on the geometric characteristics of the groove profile. A second analytical solution based on the series development was also proposed. It was proved that change of the boundary conditions of the grain grooving profile largely affected the different geometric characteristics of the groove profile.

Polymer electrolyte was used as a medium for testing the performance of microband electrodes under conditions of linear diffusion. Cyclic voltammetry and chronoamperometry experiments were performed in such viscous medium, where diffusion rates are much slower than in fluid solutions. Confirmation of the existence of such conditions from the log i vs. log v or log i vs. log t relationships in the current equation always yielded values lower than the expected value of 0.5. This could indicate impure linear diffusion profile, i. e. some contribution from radial diffusion (edge effect). However, performing these tests in monomeric solvents of similar viscosities, such as glycerol or propylene glycol, gave the desired value of 0.5. These results lead to the conclusion that current equations which are based on Fick’s laws may not be applicable for polymer electrolytes, where various obstruction to diffusion make it a more complicated process than in monomeric solvents.

The presence of phase diffusion can lead to the loss of the advantages of quantum measurements. Squeezing is considered to be an effective method to reduce the detrimental effect of phase diffusion on the measurement. The Mach-Zehnder (MZ) interferometer has been exploited as a generic tool for precise phase measurement. Describing the reduction in quantum advantage caused by phase diffusion in an MZ interferometer that can be mitigated by squeezing is not easy to handle analytically, because the input state will change from a pure state to a mixed state after experiencing the diffusion noise in the MZ interferometer. We introduce a truncated MZ interferometer that can achieve the same potential phase sensitivity as the conventional MZ interferometer. This scheme can theoretically explain how phase diffusion reduces phase estimation and why squeezing counteracts in the presence of phase diffusion. Using the Gaussian property of the input state and the characteristic of Gaussian operation in the squeezing, the two orthogonal field quantities of the quantum state are squeezed and anti-squeezed to different degrees, and the analytic results are obtained. The truncated MZ interferometer is simpler to build and operate than the conventional MZ interferometer, and also mitigates the phase diffusion noise by the squeezing operation, thus making it useful for applications in precision metrology.

We present a new mathematical model of disease spread reflecting specialties of covid-19 epidemic by elevating the role social clustering of population. The model can be used to explain slower approaching herd immunity in Sweden, than it was predicted by a variety of other mathematical models; see graphs Fig. \ref{GROWTH2}. The hierarchic structure of social clusters is mathematically modeled with ultrametric spaces having treelike geometry. To simplify mathematics, we consider homogeneous trees with $p$-branches leaving each vertex. Such trees are endowed with algebraic structure, the $p$-adic number fields. We apply theory of the $p$-adic diffusion equation to describe coronavirus' spread in hierarchically clustered population. This equation has applications to statistical physics and microbiology for modeling {\it dynamics on energy landscapes.} To move from one social cluster (valley) to another, the virus (its carrier) should cross a social barrier between them. The magnitude of a barrier depends on the number of social hierarchy's levels composing this barrier. As the most appropriate for the recent situation in Sweden, we consider {\it linearly increasing barriers.} This structure matches with mild regulations in Sweden. The virus spreads rather easily inside a social cluster (say working collective), but jumps to other clusters are constrained by social barriers. This behavior matches with the covid-19 epidemic, with its cluster spreading structure. Our model differs crucially from the standard mathematical models of spread of disease, such as the SIR-model. We present socio-medical specialties of the covid-19 epidemic supporting our purely diffusional model.

With worsening environmental degradation and increasing international demand for human health, plant cell based technology will be more important. The aim of this review is to give an overview regarding key points of current progress and development trend of nature medical and edible plants from the framework of whole plant cell engineering including cell cultures, cell fusion and cell splitting derived biotechnology. Here we sum up three main application trends of medical plants cell cultures covering industrial output, technology upgrading and potential resource development. We also provide classification and typification insights to summarize the development of somatic hybridization in cereal, vegetables crops and other medicinal and edible plants as well as application of artificial polyploidy induction in major medicinal herbs. Development medicinal and edible homologous plants based on modern plant cell engineering will bring us a promising future.

It is known that ammonium has a higher permeability through anion-exchange and bipolar membranes compared to K+ cation that has the same mobility in water. However, the mechanism of this high permeability is not clear enough. We develop a mathematical model based of the Nernst-Planck and Poisson equations for diffusion of ammonium chloride through an anion-exchange membrane; proton exchange reactions between ammonium, water and ammonia are taken into account. It is assumed that ammonium, chloride and OH− ions can only pass through membrane hydrophilic pores, while ammonia can also dissolve in membrane matrix fragments not containing water and diffuse through these fragments. It is found that due to the Donnan exclusion of H+ ions as coions, the pH in the membrane internal solution increases when approaching the membrane side facing distilled water. Consequently, there is a change in the principal nitrogen-atom carrier in the membrane: in the part close to the side facing the feed NH4Cl solution (pH&lt;8.8), it is the NH4+ cation, and in the part close to distilled water, NH3 molecules. The concentration of NH4+ reaches almost zero at a point close to the middle of the membrane cross-section, which approximately halves the effective thickness of the diffusion layer for the transport of this ion. When NH3 takes over the nitrogen transport, it only needs to pass through the other half of the membrane. Leaving the membrane, it captures an H+ ion from water, and the released OH− goes towards the membrane side facing the feed solution to meet the NH4+ ions. The comparison of the simulation with experiment shows a satisfactory agreement.

Li₂MnO₃ is critical component in the well-studied Li-excess cathode materials xLi₂MnO₃•(1- x)LiMO₂ for achieving high lithium storage capacity. In this article, the diffusion of Li ions in Li₂MnO₃ is studied using molecular dynamics (MD) simulation with well-behaved empirical force fields obtained by fitting against the crystal structure from experiment and phonons calculated using Density Function Theory (DFT). We have found two possible tetrahedral hopping channels, 0-TM and 1-TM(Mn⁴⁺) channel, which are differentiated by the face sharing octahedral cations. Simulation results show that the 0-TM channel is active for Li hopping, while 1-TM(Mn4+) channel is inactive. During the delithiation process, the Li ions in the TM layered are firstly removed, then those in the Li layer. However, the Li ions will be trapped in the tetrahedral 0-TM channels as long as the four face sharing octahedral sites are cleared. Up to x=1.0 for Li₂-xMnO₃, almost all the Li ions are located at the tetrahedral sites, forming a regular array along a axis. The de-intercalation of tetrahedral Li ions requires a high voltage (>5.2 V vs. Li/Li+), limiting the practical capacities measured in lab. The diffusion of Mn ions into the Li layers is observed in a deeper delithiated structure (x=1.2 for Li₂-xMnO₃), indicating an initial phase transformation to a spinel-like structure. However, the Mn ions are mainly trapped in the tetrahedral sites in the Li layer, instead of the octahedral sites fin spinel-like structure. A few of Mn ions diffusing into the octahedral sites in Li layers have no face sharing tetrahedral Li ions, revealing a further Li de-intercalation is imperative for the complete phase transformation. Our model is not stable for x≥1.4 in Li₂-xMnO₃. Other charge compensation mechanism should be considered in this high delithiation stage, eg. oxygen release.

The main characteristic of polycystic kidney disease is the development of multiple fluid filled renal cysts. The discovery of mislocated Na,K-ATPase in the apical membrane of cyst lining epithelia alluded to a reversal of polarity as a possible explanation to the fluid secretion. The topic of apical Na,K-ATPase in cysts remains controversial. We investigated the localization of the Na,K-ATPase and assessed the apical-basolateral polarization of cyst lining epithelia by means of immunohistochemistry in kidney tissue from six polycystic kidney disease patients undergoing nephrectomy. The Na,K-ATPase α1 subunit was conventionally situated in the basolateral membrane of all immunoreactive cysts. Proteins of the Crumbs and partitioning defective (Par) complexes were localized to the apical membrane domain in cyst epithelial cells. The apical t-SNARE protein Syntaxin-3 also immunolocalized to the apical domain of cyst lining epithelial cells. Proteins of the basolateral Scribble complex immunolocalized to the basolateral domain of cysts. Furthermore, we confirmed that cysts can originate from virtually any tubular segment with preserved polarity. In conclusion, we find no evidence of a reversal in apical-basolateral polarity in cyst lining epithelia in polycystic kidney disease.

In neonatal equines, pathologies involving umbilical structures are an important cause of morbidity, and surgical removal of urachal remnants is a common procedure in clinical practice. Surgery involving the ventral abdominal wall can cause substantial pain, leading to complications and prolonged recovery. The objectives of this study were to describe a two-point bilateral ultrasound-guided rectus sheath block at the level of the umbilicus and to evaluate the extent of dye distribution in foal cadavers. Ten foal cadavers were included in the study, in which a bilateral two-point ultrasound-guided rectus sheath block was performed—one injection cranially and a second one caudally to the umbilicus. The injectate consisted of a mixture of iodinated contrast medium and blue dye at a volume of 0.25 mL kg-1 per injection point (total 1 mL kg-1). After the injection, computer tomography and subsequent dissection of the ventral abdominal wall were performed. The extension of the contrast medium, the number of stained nerves, and contamination of the abdominal cavity were evaluated. The cranio-caudal extension of the contrast ranged from 0.8 to 1.4 centimeters per milliliter of injectate. The most commonly stained ventral branches of spinal nerves were thoracic (Th) nerves 16, 17, and 18 (95%, 85%, and 80% of the nerves, respectively). Abdominal contamination was found in 4 animals. The results suggest that the block could provide periumbilical analgesia. Further studies with different volumes of injectate and living animals are warranted.