Early reports demonstrated the presence of cells with stem-like properties in bone marrow, with these cells having both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multi-lineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and potential, MSCs are leveraged in many applications including medicine, oncology, bioprinting and as recent as treatment of COVID-19. To date, reports indicate mesenchymal stromal/stem cells have varied differentiation capabilities into different cell types and demonstrate immunomodulating and anti-inflammatory properties. Reports indicate that different MSCs microenvironments or niche and the resulting heterogeneity may influence their behavior and differentiation capacity. The potential clinical applications of mesenchymal stromal/stem cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. The future looks bright and promising for mesenchymal stem cell research with many clinical trials under way to prove their utility in many applications and in the clinic. This report provides an update on the potential broader use of mesenchymal stromal/stem cells, review early observations of the presence of these cells in the bone marrow and their magnificent differentiation capabilities and immunomodulation.

Microbial symbioses exhibit astounding adaptations, yet all symbionts face the problem of how to reliably associate with host offspring every generation. A common strategy is vertical transmission, in which symbionts are directly transmitted from the female to her offspring. The diversity of symbionts and vertical transmission mechanisms is as expansive as the diversity of eukaryotic host taxa that house them. However, there are several common themes among these mechanisms based on the degree to which symbionts associate with the host germline during transmission. In this review, we detail three distinct vertical transmission strategies, starting with associations that are transmitted from host somatic cells to offspring somatic cells, either due to lacking a germline or avoiding it. A second strategy involves somatically-localized symbionts that migrate into the germline during host development. The third strategy we discuss is one in which the symbiont maintains continuous association with the germline throughout development. Unexpectedly, the vast majority of documented vertically inherited symbionts rely on the second strategy: soma-to-germline migration. Given that not all eukaryotes contain a sequestered germline and instead produce offspring from somatic stem cell lineages, this soma-to-germline migration is discussed in the context of multicellular evolution. Lastly, as recent genomics data have revealed an abundance of horizontal gene transfer events from symbiotic and non-symbiotic bacteria to host genomes, we discuss their impact on eukaryotic host evolution.

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

Recent evidence indicates that the risk of being diagnosed with cancer in a tissue is strongly correlated (0.80) with the number of stem cell divisions accumulated by the tissue. Since cell division can generate random mutations during DNA replication, this correlation has been used to propose that cancer is largely caused by the accumulation of unavoidable mutations in driver genes. However, no correlation between the number of gene mutations and cancer risk across tissues has been reported. Because many somatic mutations in cancers originate prior to tumor initiation and the number of cell divisions occurring during tumor growth is similar among tissues, here I use whole genome sequencing information from 22,086 cancer samples and incidence data from the largest cancer registry in each continent to study the relationship between the number of gene mutations and the risk of cancer across 33 tissue types. Results show a weak positive correlation (mean = 0.14) between these two parameters in each of the five cancer registries. The correlation became stronger (mean = 0.50) when gender-related cancers were excluded. Results also show that 1,003 samples from 29 cancer types have zero mutations in genes. These data suggest that cancer etiology can be better explained by the accumulation of stem cell divisions than by the accumulation of gene mutations. Possible mechanisms by which the accumulation of cell divisions in stem cells increases the risk of cancer are discussed.

Regeneration is a fundamental process much attributed to functions of adult stem cells. In last decades delivery of suspended adult stem cells is widely adopted in regenerative medicine as a leading mean of cell therapy. However, adult stem cells can not complete the task of human body regeneration effectively by themselves as far as they need a receptive microenvironment (the niche) to engraft and perform properly. Understanding of mechanisms underlying mammalian regeneration lead us to an assumption that improved outcomes of cell therapy requires a specific microenvironment generated in damaged area prior to stem cell delivery. To certain extent it may be achieved by delivery of mesenchymal stromal cells (MSC), not in dispersed form, but rather self-organized in cell sheets (CS) – tissue-like structures comprising of viable cells and microenvironment components: extracellular matrix and soluble factors deposited in the matrix. In this communication we highlight a potential role of mesenchymal stromal cells (MSC) as regeneration organizers and speculate that this function emerges in CS. This concept shifts our understanding of therapeutic mechanism underlying a widely known CS-based delivery method for regenerative medicine.

Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population as well as an economic load to the health care system, yet treatments of these preventable cancers remain ineffective. Although primary prevention is possible through minimising sunlight exposure, the World Health Organisation estimates that between 2 and 3 million new cases of NMSCs are diagnosed each year, accounting for 1 in 3 of all newly diagnosed cancers. Furthermore, studies have estimated there has been a 2-fold increase in the incidence of NMSCs between 1960s and 1980s. The increase in cases of NMSCs as well as the lack of effective treatments makes the need for novel therapeutic approaches all the more necessary. To rationally develop more targeted treatments for NMSCs, a better understanding of the cell of origin, in addition to the underlying pathophysiological mechanisms that govern the development of these cancers, is urgent. NMSCs are generally thought to arise from specific types of stem cells that become the source of clonal expansion of tumourigenic cells. Previous research on SCC has alluded to these stem cells being localised in the basal compartment of the skin, which ordinarily houses the progenitor cells that contribute towards wound healing and normal cell turnover of overlying epidermal skin layers. More recent research has suggested that commitment to differentiation, which requires exiting the basal, progenitor-cell compartment, is a reversible mechanism. Genetic modifications engage differentiated cells into dedifferentiation, converting them into cancer-initiating cells (CICs) and thereby promoting a tumourigenic environment. Here we explore the most recent developments in the understanding of skin SCC cell of origin, and discuss a case study illustrating the loss of the Grainy-head like 3 (GRHL3) transcription factor in suprabasal layers, which confers a tendency towards tumour development and thereby challenging the “stem cell” theory of tumourigenesis.

In the paper, by the Faά di Bruno formula, several identities for the Bell polynomials of the second kind, and an inversion theorem, the authors simplify coefficients of two families of nonlinear ordinary differential equations for the generating function of the Catalan numbers and discover inverses of fifteen closely related lower triangular integer matrices.

The current work addresses the control of two-input two-output (TITO) Wood and Berry model of a binary distillation column. The controller design problem is formulated in terms of multivariable H_∞ control synthesis. The controller structure takes the form of simplest static output feedback (SOF) control. The controller synthesis is performed using a hybrid approach of blending linear matrix inequalities (LMI) and genetic algorithm (GA). The performance of the static output feedback controller is compared with three other controllers designed for Wood and Berry model available in the literature. The first simulation study is performed for the case of tracking a unit step command in the presence of a step change in output disturbance. A second simulation study is performed for rejecting a change in sinusoidal output disturbance.

Synthesis of new series of 1-phenyl-3-(4-(pyridin-3-yl) phenyl) urea derivatives and its in vitro antiproliferative activities against NCI-60 human cancer cell lines of nine different cancer types are described. Fourteen compounds 5a-n have been synthesized with three different hydrogen bondable moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure 1-phenyl-3-(4-(pyridin-3-yl) phenyl) urea. Different substituents with different π and σ values were added on the terminal phenyl group. Compounds with 4-hydroxymethylpiperidine moiety showed higher mean percentage inhibition values over the 60-cell line panel at 10-µM concentration. They showed broad-spectrum antiproliferative activity over many cell lines of different cancer types. For instance, compound 5a elicited some lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line by 146.1, 108.7, 136.2, 134.8, 116.6 % at 10 µM, respectively. Compounds 5a-e exhibited superior antiproliferative activity than Paclitaxel and Gefitinib against the most sensitive cell lines. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose testing mode to determine their IC₅₀ values. The data revealed that 5a and 5d urea compounds are the most active derivatives with significant efficacies and superior potencies than Paclitaxel in 21 different cancer cell lines, belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than Gefitinib in 38 and 34 cancer cell lines, respectively; belonging particularly to colon cancer, breast cancer and melanoma cell lines.

Passiflora cincinnata Mast is a plant popularly used in traditional medicine in northeastern Brazil. The present study aimed to evaluate the anti-lipoperoxidative and anti-α-amylase properties, and cytotoxicity of an extract and fraction of passion fruit leaves (P. cincinnata Mast), as well as the antihyperglecemiant activity of the fraction rich in glycosylated flavonoids and showing low cytotoxicity in rats with a postprandial hyperglycaemia condition. The ethyl acetate fraction (F.ACT) of the P. cincinnata leaves presented the best anti-lipoperoxide properties with TBARs 81.49%, 95.48% and 75.62% lower than AAPH, FeSO₄ and H₂O₂ induced controls, respectively, at 200 μg.mL-1. In addition, it presented an anti-α-amylase potential, with a better ability to inhibit the α-amylase enzyme in comparison to the acarbose control (IC₅₀ 6.49 ± 0.11 and 12.01 ± 0.4 μg.mL-1, respectively). The hydroalcoholic extract of P. cincinnata (ExEt) presented high content of total tannins, flavonoids and flavonols. However, F.ACT had the highest concentration of flavonoids among the fractions studied. HPLC analysis of this fraction revealed the presence of the flavonoids isovitexin, orientin and isoorientin. F.ACT showed low to no cytotoxicity below 150 μg.mL-1. Regarding the post-prandial antihyperglycaemic activity of F.ACT, it was observed at 50 and 100 mg.kg-1.

Abstract: DNA fragmentation factors 40 and 45 (DFF40 and DFF45) and B-cell lymphoma 2 (Bcl-2) expression were evaluated in the normal human endometrium and myometrium. DFF40, DFF45, and Bcl-2 expression was assessed via immunohistochemistry in the proliferative, secretory, and atrophic endometrium and myometrium collected postmenopausally and premenopausally during the proliferative and secretory phases of the menstrual cycle. The endometrium showed significantly higher DFF40 and DFF45 expression than that in the uterine myometrium; compared to the stroma, endometrial glands showed the highest expression in pre- and postmenopausal specimens. Glandular expression of DFF45 was dependent on the menstrual cycle, reaching its highest level in the secretory endometrium. The glandular expression of DFF40 and DFF45 was significantly lower in postmenopausal specimens than that in premenopausal tissue. No cycle-dependent changes were reported for stromal or myometrial DFF40 or DFF45 expression. Compared to the endometrial stroma and myometrium, Bcl-2 showed the highest expression in the glandular proliferative endometrium and the lowest expression in the stromal secretory endometrium and myometrium during the secretory phase of the cycle. DFF45 and Bcl-2 showed menstrual cycle-dependent expression, which was limited to the glandular layer of the endometrium.

This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, PDIP46 and PDIP38, both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the splicesosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, Mdm2 alternative splicing and the regulation of the Nox4 NADPH oxidase.

High-performance poly(1,4-butylene terephthalate (PBT) nanocomposites have been developed via the consideration of phosphorus-containing agents and amino-carbon nanotube (A-CNT). One-pot functionalization method has been adopted to prepare functionalized CNTs via the reaction between A-CNT and different oxidation state phosphorus-containing agents, including chlorodiphenylphosphine (DPP-Cl), diphenylphosphinic chloride (DPP(O)-Cl), and diphenyl phosphoryl chloride (DPP(O3)-Cl). These functionalized CNTs, DPP(Ox)-A-CNTs (x = 0, 1, 3), were respectively mixed with PBT to obtain the CNTs-based polymer nanocomposites through a melt blending method. SEM observations demonstrated that DPP(Ox)-A-CNT nano-additives were homogeneously distributed within PBT matrix compared to A-CNT. The incorporation of DPP(Ox)-A-CNT improved the thermal stability of PBT. Moreover, PBT/DPP(O3)-A-CNT showed the highest crystallization temperature and tensile strength, due to the superior dispersion and interfacial interactions between DPP(O3)-A-CNT and PBT. PBT/DPP(O)-A-CNT exhibited the best flame retardancy resulting from the excellent carbonization effect. The radicals generated from decomposed polymer were effectively trapped by DPP(O)-A-CNT, leading to the reduction of heat release rate, smoke production rate, carbon dioxide and carbon monoxide release during cone calorimeter tests.

Corneal ulcer (CU) is an ophthalmopathy characterized by depression of the corneal surface with at least one stromal loss. CU is common in canine and feline species and is usually caused, among others, by trauma, infections, toxic contamination and endocrine disorders. They usually result from an increased inflammatory response and are associated with some clinical signs such as blepharospasm, photophobia, epiphora, pain and loss of corneal transparency. Despite advances in conventional and pharmacological therapy, in many cases indolent and recurrent ulcer treatments still lead to loss of visual acuity of the animal. This paper aims to report the effect of topical application of canine adipose tissue-derived mesenchymal stem cell (cATMSCs) as treatment of recurrent CU in a Poodle dog breed that showed clear difficulty in the healing process associated with diabetes. The animal was submitted to two applications of cATMSCs and showed improvement in the blepharospasm, conjunctival hyperemia, mucopurulent ocular secretion, photophobia, corneal opacity, chemosis, pigmentation, neovascularization, and pain parameters. Besides, Fluorescein test, Schirmer test and ocular fundus exam also showed improvement in their values concomitantly with lesion resolution. Due this, we showed that cATMSC therapy contribute to the regeneration of corneal tissue in CU and may contribute to the treatment to others ophthalmopathies.

Background: Renal cancers are among the top ten causes of cancer-specific mortality, of which the ccRCC subtype is responsible for most cases. The grading of ccRCC is important in determining tumour aggressiveness and clinical management. Objectives: The objectives of this research were to predict the WHO/ISUP grade of ccRCC pre-operatively and characterise the heterogeneity of tumour sub-regions using radiomics and ML models, including comparison with pre-operative biopsy-determined grading in a sub-group. Methods: Data were obtained from multiple institutions across two countries, including 391 patients with pathologically proven ccRCC. For analysis, the data were separated into four cohorts. Cohorts 1 and 2 included data from the respective institutions from the two countries, cohort 3 was the combined data from both cohort 1 and 2, and cohort 4 was a subset of cohort 1, for which both the biopsy and subsequent histology from resection (partial or total nephrectomy) were available. 3D image segmentation was carried out to derive a voxel of interest (VOI) mask. Radiomics features were then extracted from the contrast-enhanced images, and the data were normalised. The Pearson correlation coefficient and the XGBoost model were used to reduce the dimensionality of the features. Thereafter, 11 ML algorithms were implemented for the purpose of predicting the ccRCC grade and characterising the heterogeneity of sub-regions in the tumours. Results: For cohort 1, the 50% tumour core and 25% tumour periphery exhibited the best performance, with an average AUC of 77.9% and 78.6%, respectively. The 50% tumour core presented the highest performance in cohorts 2 and 3, with average AUC values of 87.6% and 76.9%, respectively. With the 25% periphery, cohort 4 showed AUC values of 95.0% and 80.0% for grade prediction when using internal and external validation, respectively, while biopsy histology had an AUC of 31.0% for the classification with the final grade of resection histology as a reference standard. The CatBoost classifier was the best for each of the four cohorts with an average AUC of 80.0%, 86.5%, 77.0% and 90.3% for cohorts 1, 2, 3 and 4 respectively. Conclusion: Radiomics signatures combined with ML have the potential to predict the WHO/ISUP grade of ccRCC with superior performance, when compared to pre-operative biopsy. Moreover, tumour sub-regions contain useful information that should be analysed independently when determining the tumour grade. Therefore, it is possible to distinguish the grade of ccRCC pre-operatively to improve patient care and management.

This paper extends the concept of weighted graphs to matrix weighted graphs. The consensus algorithms dictate that all agents reach consensus when the weighted graph is connected. However, it is not always the case for matrix weighted graphs. The conditions leading to different types of consensus have been extensively analysed based on the properties of matrix-weighted Laplacians and graph theoretic methods. However, in practice, there is concern on how to pick matrix-weights to achieve some desired consensus, or how the change of elements in matrix weights affects the consensus algorithm. By selecting the elements in the matrix weights, different clusters may be possible. In this paper, we map the roles of the elements of the matrix weights in the systems consensus algorithm. We explore the choice of matrix weights to achieve different types of consensus and clustering. Our results are demonstrated on a network of three agents where each agent has three states.

COVID-19 sepsis immune response remains unclear. Here we propose a new perspective in host response against pathogenic proteins that may lead to a vaccine design by polymerization of antigens of <70 kDa. In COVID-19, initial Th1 response kills infected cells releasing viral proteins. SARS-CoV-2 viral structural proteins are Spike (140 kDa), Nucleocapsid (50 kDa), Membrane (25 kDa) and Envelope (10 kDa). B cell receptor cannot capture antigens >70 kDa. The Spike protein (140 kDa) cannot be captured by B cells and triggers inflammatory Th1 response via the macrophages. Only proteins with a size <70 kDa can activate B cell receptor and trigger Th2 adaptative humoral response. Moreover, M-25 kDa and E-12 kDa glycoproteins can activate IgM-BCR like oligovalent or monovalent antigens. The sustained infected cells lysis overfeeds high levels of viral proteins <70 kDa, increases B cells activation and, in the shift from Th1 to Th2 immune response, triggers the cytokine storm. The continuous BCR activation increases IL-10 releasing and may lead to immune paralysis.

A critical quality attribute of therapeutic monoclonal antibodies (mAbs) is the terminal sugar molecules of the N-linked glycan attached to the fragment crystalizable (Fc) region. There exists naturally-occurring heterogeneity in the N-linked glycan structure of mAbs, and such heterogeneity has a significant influence on the clinical safety and efficacy of mAb drugs. We previously proposed a constraint-based modeling method called glycosylation flux analysis (GFA) to characterize the rates (fluxes) of intracellular glycosylation reactions and applied the method to examine the N-linked glycosylation of immunoglobulin G (IgG) in fed-batch Chinese hamster ovary (CHO) fed-batch cultivations. In this work, we significantly improved the computational efficiency of the GFA, and employed the method to analyze the glycosylation of IgG in continuous perfusion CHO cultivations. Perfusion cell cultures have several advantages over the traditional (fed-)batch operation, including higher productivity per unit volume of reactor and more consistent product quality. The GFA showed that as in the fed-batch cultivation, the dynamical changes of IgG glycan heterogeneity in the perfusion culture are mainly attributed to alterations in the galactosylation flux activity. Furthermore, a regression analysis of the galactosylation flux activity using random forest regression linked the dynamics of galactosylation activity with the cell-specific productivity of IgG and the extracellular ammonia concentration.

Though the cancer research community has used mouse xenografts for decades more than zebrafish xenografts, zebrafish have much to offer: they are cheap, easy to work with, and the embryonic model is relatively easy to use in high-throughput assays. Zebrafish can be imaged live, allowing us to observe cellular and molecular processes in vivo in real time. Opponents dismiss the zebrafish model due to the evolutionary distance between zebrafish and humans, as compared to mice, but proponents argue for the zebrafish xenograft’s superiority to cell culture systems and its advantages in imaging. This review places the zebrafish xenograft in the context of current views on cancer and gives an overview of how several aspects of this evolutionary disease can be addressed in the zebrafish model. Zebrafish are missing homologs of some human proteins and (of particular interest) several members of the matrix metalloproteinase (MMP) family of proteases, which are known for their importance in tumour biology. This review draws attention to the implicit evolutionary experiment taking place when the molecular ecology of the xenograft host is significantly different than that of the donor.

Transfer factor is the name given to material derived from activated lymphocytes that is probably composed of a complex of a peptide and a short segment of RNA and which has the reported ability to transfer specific T cell immunity to uncommitted lymphocytes. Many independent groups around the world reported isolating transfer factors between 1955 and 1990 and demonstrating their ability to transfer passive immunity from one animal or individual to another, often within 24 hours of inoculation. Such activity is potentially revolutionary both in making T cell vaccines readily manufacturable and also because the existence of transfer factors would undermine the basic assumptions of the clonal selection theory, which currently dominates immunological theory. Unfortunately, lack of the microanalytical and synthetic techniques required to properly identify transfer factors, combined with safety factors associated with it derivation from blood sources susceptible to HIV and prion infections, put an end to transfer factor research after 1990. This paper reviews the evidence supporting transfer factor activity and suggests that this potentially revolutionary concept be resurrected and subjected to renewed scrutiny in light of CRISPR-Cas mechanisms and because of its potential to make possible T cell vaccination and provide a novel basis for understanding immunological function.

The cell’s capacity to integrate and respond to spatial information is a crucial feature of morphogenesis and development. The Planar Cell Polarity (PCP) pathway is a signaling mechanism, widely conserved across metazoans, providing spatial orientation along the plane of an epithelium in morphogenic processes ranging from insect wing patterning to mammalian cochleae. Although the core genes involved in the PCP pathway have been molecularly identified in the 1990s, the PCP signaling mechanism remains controversial. In this article I discuss the main players and previous models of PCP signaling reported in the literature, and propose a new model. According to it PCP is established through an homophobic signal by transmembrane protein Frizzled (Fz): 1) a Fz signal in one cell repeals Fz itself in the adjacent cell, thereby generating symmetry breaking; 2) the instructive PCP signal is conveyed through Fz interaction with atypical cadherin Flamingo (Fmi). More broadly, homophobic signaling may represent a novel mechanism for cell-cell signaling of spatial information through modulation of cell adhesion rather than canonical ligand-receptor binding.

Natural carotenoids are secondary metabolites that exhibit antioxidant, anti-inflammatory and anti-cancer properties. These types of compounds are in high demand by pharmaceutical, cosmetic, textile and food industries, leading to the search for new natural sources of carotenoids. In recent years, the production of carotenoids from bacteria has become of great interest for industrial applications. In addition to carotenoids with C40-skeletons, some bacteria have the ability to synthesize characteristic carotenoids with C30-skeletons. In this regard, a great variety of methodologies for the extraction and identification of bacterial carotenoids has been reported and this is the first review that condenses much of this information. To understand the diversity of these carotenoids, we present their biosynthetic origin in order to focus on the methodologies employed in their extraction and characterization. Special emphasis has been made on high-performance liquid chromatography-mass spectrometry (HPLC-MS) for the analysis and identification of bacterial carotenoids. We end up this review showing their potential commercial use of bacterial carotenoids. This review is proposed as a guide for the identification of these metabolites, which are frequently reported in new bacteria strains.

This paper deals with a generic methodology to evaluate the magnetic parameters of contactless power transfer systems. Neumann's integral has been used to create a matrix method that can model the magnetics of single coils (circle, square, rectangle). The principle of superposition has been utilised to extend the theory to multi-coil geometries such as double circular, double rectangle and double rectangle quadrature assuming linearity of magnetics. Numerical and experimental validation has been performed to validate the analytical models developed. A rigorous application of the analysis has been carried out to study misalignment and hence the efficacy of various geometries to misalignment tolerance. Comparison of single-coil and multi-coil shapes considering coupling variation with misalignment, power transferred and maximum efficiency is carried out.

Psoriasis (PS) is an autoimmune skin disease mediated by immune cells that typically presents inflammatory erythematous plaques, and it is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature and reside in vascularized tissues. They can be activated by antigen provoking overexpression of pro-inflammatory cytokines and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophage to release IL-36, a powerful pro-inflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic pro-inflammatory diseases such as psoriasis. Suppressing IL-36 results in a noticeable improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra which binds on to IL-36 receptor ligand, but suppression can also occur by binding IL-38 to the IL-36R receptor. IL-38 specifically binds only to IL-36R and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs, a process that activates macrophages to secrete pro-inflammatory IL-36 inhibited by IL-38. In this article we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis and hold promise of an innovative therapeutic tool.

Brain cancer is the tenth leading cause of death in the U.S. Glioblastoma multiforme (GBM) is the most lethal primary malignant central nervous system tumor in adults. The present study employed samples from 1985-2014 to discover the difference in prognosis among glioblastoma subtypes after the evolution of treatment modalities over the past few years. The current study aims to find the differences between Glioblastoma multiforme (GBM) and giant cell glioblastoma (GCG) in terms of prognosis among adults and elderly patients in the U.S. This study is a historical cohort type of study and is conducted on adults and elderly individuals with GBM or GCG from the years 1985-2014 in the U.S. Data were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database. The study exposure was GBM or GCG and the outcome was mortality. The potential confounders were age, sex, race, ethnicity, year of diagnosis, primary site, and surgery. A chi-square test was used for categorical data. A univariate analysis was used for variables having a p-value < 0.05. Potential confounders were selected and evaluated using multivariate logistic regression models to calculate the odds ratio with stepwise selection. The study sample was 25,117. The incidences of GBM and GCG were not similar in relation to age group. Also, Spanish-Hispanic ethnicity was independently protective of GBM and GCG as compared to Non-Spanish-Hispanic ethnicity patients with GBM have a higher mortality rate than do GCG patients. The mortality rate was higher among patients diagnosed before 2010. In conclusion, GCG was not statistically significant in association to reduced mortality. Non-Spanish-Hispanics with GBM or GCG had a higher mortality rate than did Spanish-Hispanics. Factors such as being female, being age >59, and having a year of diagnosis before 2010 were independently associated with increased mortality.

The epidermis is the outermost layer of skin and provides a protective barrier against environmental insults. It is a rapidly renewing tissue undergoing constant regeneration, maintained by several types of stem cells. Hedgehog (HH) ligands activate one of the fundamental signaling pathways that contribute to epidermal development, homeostasis and repair. The HH pathway interacts with other signal transduction pathways such as those activated by Wnt and bone morphogenetic protein. Furthermore, aberrant activation of HH signaling is associated with various tumors, including basal cell carcinoma. Therefore, an understanding of the regulatory mechanisms of the HH signaling pathway is important to elucidate fundamental mechanisms underlying both organogenesis and carcinogenesis. In this review, we discuss the role of the HH signaling pathway in skin development, homeostasis and basal cell carcinoma formation, providing an update of current knowledge in this field.

Energy harvesting from wind turbines has been explored by researchers for more than a century from conventional turbines up to the latest bladeless turbines. Amongst these bladeless turbines, vortex bladeless wind turbine (VBT) harvests energy from oscillation of a turbine body. Due to the novelty of this science and the widespread researches around the world, one of the most important issues is to optimize and predict produced power. To enhance the produced output electrical power of VBT, the fluid-solid interactions (FSI) were analyzed to collect a dataset for predicting procedure. Long short-term memory (LSTM) method has been used to predict the produced power of VBT from the collected data. The reason of choosing LSTM from various artificial neural network methods is that the parameters of VBT study are all time- dependent and the LSTM is one of the most accruable algorithms for predicting time series data. In order to find the relationship between the parameter and the variables used in this research, a correlation matrix was presented. According to the value of 0.3 for the root mean square error (RMSE), a comparative analysis between the simulation results and its prediction shows that the LSTM method is very accurate for these types of research. Furthermore, the LSTM method has significantly reduced the computation time so that the prediction time of desired values has been reduced from an average of 2 and a half hours to two minutes. Also, one of the most important achievements of this study is to suggest a mathematical relation of VBT output power which helps to extend it in a different size of VBT with a high range of parameter variations.

The present Feature Paper highlights the application of bacterial surface (S-) layer proteins as versatile components for the fabrication of biosensors. One technologically relevant feature of S‑layer proteins is their ability to self-assemble on many surfaces and interfaces to form a crystalline 2D protein lattice. The S-layer lattice on the surface of a biosensor becomes part of the interface architecture, linking the bioreceptor to the transducer interface, which may cause signal amplification. The S-layer lattice as ultrathin, highly porous structure with functional groups in a well-defined special distribution and orientation and an overall anti-fouling characteristics can significantly raise the limit in terms of variety and ease of bioreceptor immobilization, compactness of bioreceptor molecule arrangement, sensitivity, specificity, and detection limit for many types of biosensors. The present paper discusses and summarizes examples for the successful implementation of S-layer lattices on biosensor surfaces in order to give a comprehensive overview on the application potential of these bioinspired S-layer protein-based biosensors.

The aim of this article is to evaluate and compare, retrospectively, the efficacy of two regenerative periodontal procedures in patients suffering from aggressive periodontitis (AgP). Twenty-eight patients were diagnosed with AgP, suffering from multiple intra-bony defects (IBD); that were treated by one of two regenerative modalities of periodontal therapy randomly assigned to each patient: a. guided tissue regeneration (GTR) or b. an application of enamel matrix derivatives (EMD) combined with DBX. The monitoring of the treated sites included recordings of probing depth (PD), clinical attachment level (CAL), and gingival recession. Pre-treatment and follow-up (up to 10 years from the surgery) recordings were analyzed statistically within and between groups. A significant reduction was shown at time on PD and CAL values, however, not between subject groups. CAL values decreased in all sites. At EMD group (44 sites) CAL gain was 1.92 mm (±1.68) from pre-treatment to follow-up (p<0.001) and at the GTR group (12 sites) CAL gain of 2.27 (±1.82) mm. In conclusion, 1-10 years observations have shown that surgical treatment of AgP patients by either GTR or by application of EMD/DBX results in similar successful clinical results.

Background: As noninvasive prenatal screening usage grows in the general obstetrics setting, proper patient education on the screen’s benefits and limitations is needed. Objective: Describe the use of a technology platform designed for large-scale dissemination of noninvasive prenatal screening information and results. Study Design: The technology platform functioned as follows: Patients were emailed a link to an noninvasive prenatal screening general-education video upon laboratory receipt of a test requisition. Providers were then notified upon availability of patients’ results. If noninvasive prenatal screening results were negative, the patient was sent an automated email with instructions to access results through a secure portal where she could watch tailored informational videos, request “on-demand” or scheduled genetic counseling, or decline any further services. If genetic counseling was elected, a summary of the session was sent to the ordering provider and patient upon completion. If noninvasive prenatal screening results were positive, either the ordering provider or a board-certified genetic counselor contacted the patient directly to communicate test results and provide counseling. The number and type of results issued through the platform, the number and type of genetic counseling consultations completed, and factors associated with requesting laboratory-delivered genetic counseling were tracked and analyzed for a 39-month period. Results: Over the study period, 67,122 noninvasive prenatal screening results were issued through the platform, and 4,673 patients elected genetic counseling consultations; 95.2% (n=4,450) of consultations were for patients receiving negative results. Over 70% (n= 3,370) of consultations were on-demand rather than scheduled. Median consultation time was 14 minutes for positive results and six minutes for negative results. A positive screen, advanced maternal age, family history, previous history of a pregnancy with a chromosomal abnormality, and other high-risk pregnancy were associated with the greatest odds of electing laboratory-delivered genetic counseling. Conclusions: By combining web education, automated notifications, and genetic counseling, we implemented a service that effectively facilitates results disclosure for ordering providers. These data demonstrate the capability to deliver noninvasive prenatal screening results, education, and counseling—congruent with management guidelines—to a large population, which is imperative to quality care as uptake increases.

Due to low working temperature, high energy density and low pollution, proton exchange fuel cells have been investigated under different operating conditions in different applications. Using platinum catalysts in methanol fuel cells leads to increasing the cost of this kind of fuel cell which is considered as a barrier to the commercialism of this technology. For this reason, a lot of efforts have been made to reduce the loading of the catalyst required on different supports. In this study, carbon black (CB) and carbon nanotubes (CNT) have been used as catalyst supports of the fuel cell as well as using the double-metal combination of platinum-ruthenium (PtRu) as anode electrode catalyst and platinum (Pt) as cathode electrode catalyst. The performance of these two types of electro-catalyst in the oxidation reaction of methanol has been compared based on electrochemical tests. Results showed that the carbon nanotubes increase the performance of the micro-fuel cell by 37% at maximum power density, compared to the carbon black. Based on thee-electrode tests of chronoamperometry and voltammetry, it was found that the oxidation onset potential of methanol for CNT has been around 20% less than CB, leading to the kinetic improvement of the oxidation reaction. The current density of methanol oxidation reaction increased up to 62% in CNT sample compared to CB supported one, therefore the active electrochemical surface area of the catalyst has been increased up to 90% by using CNT compared to CB which shows the significant rise of the electrocatalytic activity in CNT supported catalyst. Moreover, the resistance of the CNT supported sample to poisonous intermediate species has been found 3% more than CB supported one. According to the chronoamperometry test results, it was concluded that the performance and sustainability of the CNT electro-catalyst show remarkable improvement compared to CB electro-catalyst in the long term.

Light microscopy is indispensable for analysis of bacterial spatial organization. However, imaging in bacteria is difficult due to their small sizes and the fact that most species are non-spherical, meaning they typically lie horizontally on a microscope coverslip. This is especially problematic when considering that many essential bacterial processes—such as cell division—occur along the short axes of these cells, and so are viewed side-on by standard microscopy. We recently developed a pair of methods to overcome this problem by forcing cells to stand vertically during imaging, named VerCINI (Vertical Cell Imaging by Nanostructured Immobilisation) and µVerCINI (Microfluidic VerCINI). The concept behind both methods is that cells are imaged while confined vertically inside cell traps made from a nanofabricated mould. By doing so, the short axes of the cells are rotated parallel to the microscope imaging plane and are imaged with high resolution. μVerCINI combines the vertical cell confinement with microfluidics so that vertical imaging can be done during fluid exchange, such as during antibiotic perturbations. Here, we provide a practical guide to implementing both VerCINI and µVerCINI, with detailed protocols and experience-based tips so that interested researchers can easily use one or both imaging methods to complement their current approaches.

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses concerning SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear IgG B-cell epitopes in its Spike glycoprotein with a SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. Bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA assay for anti-SARS-CoV-2 antibodies. Higher reactivity indices were often measured in individuals with a pre-pandemic dengue infection than those with COVID-19. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infection of monocytes was observed with pre-pandemic dengue-positive sera. A significant increase in viral load was measured compared to controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. This study highlights the importance of identifying the epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future conditions on disease. Vaccine development and optimization strategies should be mindful of the potential for A.D.E. that could differ geographically due to endemic biological risks.

Importance: The COVID-19 pandemic is currently accelerating. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) may require treatment in locations where resources are limited and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk for severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Observation: We present expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are to reduce the number of visits to a healthcare facility, reduce the risk of SARS-CoV-2 exposure, and attenuate the immunocompromising effects of lung cancer therapies. Patients with resectable disease can be treated with definitive non-operative management if surgical resources are limited or the risks of perioperative care are high. Non-operative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules. The order of treatments may be based on patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually cancer therapies may be withheld until symptoms have resolved with negative viral test results. Conclusions and Relevance: The risk of severe treatment-related morbidity and mortality is significantly elevated for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.

A multiscale (micro-macro) approach is proposed for the establishment of the full thermal and induced stress fields in cracked composites that are subjected to heat flow. Both the temperature and stresses distributions are determined by the solution of a boundary value problem with one-way coupling. In the micro level and for combined thermomechanical loading, a micromechanical analysis is employed to determine the effective moduli, coefficients of thermal expansion and thermal conductivities of the undamaged composite. In the macro level, the representative cell method is employed according to which the periodic damaged composite region is reduced, in conjunction with the discrete Fourier transform, to a finite domain problem. As a result, a boundary value problem is obtained in the Fourier transform domain which is appropriately discretized and solved. The inverse transform and an iterative procedure provide the full thermal and stress fields. The proposed method is verified by comparisons with exact solutions. Applications are given for the determination of the thermal and stress fields in cracked fiber-reinforced polymeric composite, cracked porous ceramic material and cracked periodically layered ceramic composite caused by the application of heat flow. The presented formulation admits however the application of a combined mechanical and heat flux on cracked composites.

Understanding the evolutionary role of environmentally-induced phenotypic variation (i.e., environmental plasticity) is an important issue in developmental evolution. One of the major physiological responses to environmental changes is cellular stress, which is counteracted by a generic stress reaction that detoxifies the cell, refolds proteins, and repairs DNA damage. In this paper, we elaborate on a previous finding suggesting that the cell differentiation cascade of human decidual stromal cells, a cell type critical for embryo implantation and the maintenance of pregnancy, evolved from a cellular stress reaction. We hypothesize that the stress reaction in these cells was elicited ancestrally through the inflammation caused by embryo attachment and invasion. We describe a model, Stress-Induced Evolutionary Innovation (SIEI), whereby ancestral stress reactions and their corresponding pathways can be transformed into novel structural components of body plans, such as new cell types. After reviewing similarities and differences between SIEI and the “plasticity first hypothesis” (PFH) of evolution, we argue that SIEI is a distinct form of plasticity-based evolutionary change because it leads to the origin of novel structures rather than the adaptive transformation of a pre-existing character.

Equal-Channel Angular Pressing (ECAP) is a method used to introduce severe plastic deformation into a metallic billet without changing its geometry. In special cases strain localization occurs and a pattern consisting of regions with high and low deformation (so-called shear and matrix bands) can emerge. This paper studies this phenomenon numerically adopting two-dimensional finite element simulations of one ECAP pass. The mechanical behavior of aluminum is modeled using phenomenological plasticity theory with isotropic or kinematic hardening. The effects of the two different strain hardening types are investigated numerically by systematic parameter studies: While isotropic hardening only causes minor fluctuations in the plastic strain fields, a material with high initial hardening rate and sufficient strain hardening capacity can exhibit pronounced localized deformation after ECAP. The corresponding finite element simulation results show a regular pattern of shear and matrix bands. This result is confirmed experimentally by ECAP-processing of AA6060 material in a severely cold worked condition, where microstructural analysis also reveals the formation of shear and matrix bands. Excellent agreement is found between the experimental and numerical results in terms of shear and matrix band width and length scale. The simulations provide additional insights regarding the evolution of the strain and stress states in shear and matrix bands.

Abstract Traditional plants are known to contain a wide array of secondary metabolites with important biological activity, including anticancer activity. One of such metabolites is saponin; a steroidal or triterpenoid glycoside that is distinguished by its soap forming nature. Different saponins have been characterized and purified so far, and are gaining attention in cancer chemotherapy. Saponins possess incredible structural diversity which has been linked to their activity. They have been implicated in cancer chemoprevention and chemotherapy. Several studies have reported the role of saponins in cancer and their mechanism of actions including cell cycle arrest, antioxidant, cellular invasion inhibition, induction of apoptosis and autophagy. Despite the extensive research and significant anticancer effect of saponins there are no known FDA approved saponin based anticancer drugs due to a number of limitations including toxicities and drug likeness properties. Recent studies have explored options such as structural optimization, combination therapy and drug delivery systems to design saponins with increased efficacy and decreased toxicities. This review discussed the current knowledge on different saponins, their anticancer activity, mechanism of action as well as the current promising research on saponins within the last two decades and recommendations for future studies.

Gymnema sylvestre is a pharmacological plant which has a rich source of bioactive compounds specifically gymnemic acid (GA) and phenolic compounds (PC) that used for pharmaceutical industries. Sources for naturally occurring bioactive compounds are limited, due to geographical and seasonal variations; on the other hand, it is commercially in demand. Biosynthesis of G. sylvestre phytochemicals through in vitro culture often enhanced by elicitation. The use of cell suspension cultures (CSC) has interested serious attention on the production of essential phytochemicals. The current study is aimed at improving the contents of GA and PC in G. sylvestre CSC using the copper oxide nanoparticles (CuO NPs). Callus was obtained on MS medium with 2.0 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D), 0.1 mg/L kinetin (KIN), phytoagar (8.0 g/L), and sucrose (30 g/L). The above medium devoid of agar was used for the initiation of CSC. The CSC was treated with three levels of CuO NPs (1, 3 or 5 mg/L) to enhance the production of GA and PC. The greatest amount of GA (89.25 mg/g dry cell mass, DCM), total phenolic (245.10 mg/g), and flavonoid (4.57 mg/g) in CSC were achieved when G. sylvestre cells were treated for 48 h with 3 mg/L CuO NPs. Also, the biomedical potential (antioxidant, antidiabetic, anti-inflammatory, antibacterial, antifungal and anticancer activities) were also high in the CuO NPs (3 mg/L) treated CSC extracts of G. sylvestre. CuO NPs elicitation of CSC significantly increased production of GA (9-fold), and PC than non-elicited CSC in G. sylvestre.

The focus of this research is to improve the performance of dye-sensitized solar cells (DSSC) through the adoption of high-quality FTO thin films and incorporation of graphene with DSSC photoanode to enhance its electrical transport. In this research, nanostructured FTO films were first grown with homemade Streaming Process for Electroless and Electrochemical Deposition technology (SPEED) using Tin (II) chloride dihydrate and ammonium fluoride and other chemical formulations. The FTO structural property was measured by X-ray diffraction (XRD); the films’ optical property was determined with transmittance spectra to curve over the wavelength range of 200-1000 nm measured with a spectrophotometer while scanning electron microscope (SEM) was used to determine the morphological properties of the samples. The electrical transport was evaluated by Hall Effect measurements at room temperature with a four-point probe. The FTO samples with the best structural, optical and electrical properties were employed as electrodes and counter electrodes of DSSC along with titanium dioxide. Thus, effect of graphene on the efficiency of DSSC was investigated. It was shown that a graphene-based DSSC showed an efficiency of 7.98% which is slightly higher than that of DSSC prototype without graphene (6.02%). The higher efficiency obtained with graphene can be credited to the ultrahigh surface area and thermal conductivity of graphene which tend to enhance the charge mobility and photovoltaic performance of DSSC. More research is however required to determine the exact amount of graphene that could achieve optimal DSSC performance. Further studies will also offer an adequate clarification for starting point of the better incorporation of graphene in DSSCs.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs), including docosahexaenoic acid (DHA), have been shown to exert anticancer effects by inducing apoptotic cell death. However, the mechanism for DHA-induced cell death in lung cancer is not fully understood. Here, we show that DHA induces apoptosis in two human EGFR mutant non-small cell lung cancer (NSCLC) cell lines, and that DHA-induced cell death is accompanied by SIRT6 activation and attenuated Hedgehog (Hh) signaling. Knockdown of SIRT6 using siRNAs inhibited DHA-induced apoptosis, whereas SIRT6 overexpression increased apoptotic cell death. DHA-induced SIRT6 activation was associated with downregulation of Hh signaling, and knockdown of SIRT6 resulted in augmentation of Hh signaling. Pretreatment of NSCLC cells with a Smoothened agonist prevented DHA-induced decreases in the levels of Hh signaling proteins and increases in cleaved PARP levels. Moreover, endogenous production of ω3-PUFAs in PC9 cells via fat-1 expression resulted in elevated SIRT6 levels and reduced levels of Hh signaling molecules, including Gli, following DHA treatment. Overall, these results implicate that ω3-PUFAs induce apoptosis by downregulating Hh signaling via SIRT6 activation in human EGFR mutant NSCLC cells. These findings suggest that ω3-PUFAs potentially represent an effective therapy for the chemoprevention and treatment of NSCLC.

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

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

Energy is a fundamental ingredient in economic development and energy consumption is an index of prosperity and the standard of living. The consumption of energy has increased significantly in the last number of decades, as the standard of living has improved. Renewable energy is a sustainable and clean source of energy derived from nature. Renewable energy technology is one of the solutions, which produces energy by transforming natural resources into useful energy forms. When you do something for the first time in the world, you never attain a perfect product or solution from the start. In Central Greece Lamia city, we are the first to design and implement an off-grid energy system using hydrogen energy storage technology and phase change materials for a house residence. The action plan for energy efficiency, a series of directives and incentive mechanisms, mandatory energy certification of buildings, indicate the urgent need to reduce energy consumption in buildings, which results in a more comfortable living, long service life of buildings, which in turn preserves the environment.

The performance in terms of minimal Bayes’ error probability for detection of a high-dimensional random tensor is a fundamental under-studied difficult problem. In this work, we consider two Signal to Noise Ratio (SNR)-based detection problems of interest. Under the alternative hypothesis, i.e., for a non-zero SNR, the observed signals are either a noisy rank-R tensor admitting a Q-order Canonical Polyadic Decomposition (CPD) with large factors of size Nq  R, i.e, for 1  q  Q, where R, Nq ! ¥ with R1/q/Nq converge towards a finite constant or a noisy tensor admitting TucKer Decomposition (TKD) of multilinear (M1, . . . ,MQ)-rank with large factors of size Nq  Mq, i.e, for 1  q  Q, where Nq,Mq ! ¥ with Mq/Nq converge towards a finite constant. The detection of the random entries (coefficients) of the core tensor in the CPD/TKD is hard to study since the exact derivation of the error probability is mathematically intractable. To circumvent this technical difficulty, the Chernoff Upper Bound (CUB) for larger SNR and the Fisher information at low SNR are derived and studied, based on information geometry theory. The tightest CUB is reached for the value minimizing the error exponent, denoted by s?. In general, due to the asymmetry of the s-divergence, the Bhattacharyya Upper Bound (BUB) (that is, the Chernoff Information calculated at s? = 1/2) can not solve this problem effectively. As a consequence, we rely on a costly numerical optimization strategy to find s?. However, thanks to powerful random matrix theory tools, a simple analytical expression of s? is provided with respect to the Signal to Noise Ratio (SNR) in the two schemes considered. A main conclusion of this work is that the BUB is the tightest bound at low SNRs. This property is, however, no longer true for higher SNRs.

An accumulating body of evidence suggests that physiological reactive oxygen species (ROS) generated by NADPH oxidases act as a redox signal to re-establish homeostasis, a capacity that progressively declines during aging, but is maintained in long-lived animals to promote healthy aging. In the model organism Caenorhabditis elegans, ROS generated by dual oxidases (Duox) are important for extracellular matrix integrity, pathogen defense, oxidative stress resistance, and longevity. The Duox enzymatic activity is tightly regulated and under cellular control. Developmental molting cycles, pathogen infections, toxins, mitochondrial-derived ROS, drugs, and small GTPases (RHO-1) can activate Duox (BLI-3) to generate ROS, whereas NADPH oxidase inhibitors and negative regulators, such as MEMO-1, can inhibit Duox to generate ROS. Three mechanisms-of-action have been discovered for the Duox/BLI-3-generated ROS: 1) enzymatic activity to catalyze cross-linking of free tyrosine ethyl ester in collagen bundles to stabilize extracellular matrices, 2) high ROS bursts/levels to kill pathogens, and 3) Redox signaling activating downstream kinase cascades to transcription factors orchestrating oxidative stress- and immunity responses to re-establish homeostasis. Although Duox function at the cell surface is well established, recent genetic and biochemical data also suggests a novel role for Duoxs at the endoplasmic reticulum membrane to control redox signaling. Evidence underlying these mechanisms initiated by ROS from NADPH oxidases and their relevance for human aging are discussed in this review. Appropriately controlling NADPH oxidase activity for local and physiological redox signaling to maintain cellular homeostasis might be a therapeutic strategy to promote healthy aging.

A series of novel asymmetrical mono-carbonyl analogs of curcumin (AMACs) were synthesized and evaluated for cytotoxic activity using the brine shrimp lethality test (BSLT) and the methyl thiazolyl tetrazolium assay against Vero, HeLa, and MCF7 cell lines. The structures of the synthesized compounds were confirmed by Fourier transform infrared spectrophotometry (FTIR), ¹H-nuclear magnetic resonance (NMR), ¹³C-NMR, and mass spectral data. The results of the cytotoxicity evaluation showed that the synthesized compounds exhibited moderate to very high toxic activity in BSLT, requiring a concentration of 13.06–714.49 µg/mL to kill half the population. Most of the compound exhibited cytotoxic activity against HeLa cell lines, comparable to the activity of cisplatin with a concentration of the synthesized compounds required to inhibit 50% of the growth of the cell lines (IC₅₀) value of 40.65–95.55 µM, and most of the compounds tested against MCF7 cell lines exhibited moderate to very high cytotoxic activity (IC₅₀ value 7.86–35.88 µM). However, the selectivity index of the compounds was low, less than 1–1.96. Among the synthesized compounds, compound 1b showed the highest cytotoxicity and selectivity against MCF7 cell lines. Compound 1b could be considered for further development to obtain more active and selective chemotherapeutic agents against breast cancer.

With an estimated 3 to 5 million human cases annually and the potential to infect domestic and wild animal populations, influenza viruses are one of the greatest health and economic burdens to our society [1] and pose an ongoing threat of large-scale pandemics. Despite our knowledge of many important aspects of influenza virus biology, there is still much to learn about how influenza viruses replicate in infected cells, for instance how they use entry receptors or exploit host cell trafficking pathways. These gaps in our knowledge are due, in part, to the difficulty of directly observing viruses in living cells. In recent years, advances in light microscopy, including super-resolution microscopy and single-molecule imaging, have enabled many viral replication steps to be visualised dynamically in living cells. In particular, the ability to track single virions and their components, in real time, now allows specific pathways to be interrogated providing new insights to various aspects of the virus-host cell interaction. In this review, we discuss how state-of-the-art imaging technologies, notably quantitative live-cell and super-resolution microscopy, are shedding new nanoscale and molecular insights into influenza virus replication and revealing new opportunities for developing antiviral strategies.

Collisions of low energy electrons with molecules are important for understanding many aspects of the environment and technologies. Understanding the processes that occur in these types of collisions can give insights into plasma etching processes, edge effects in fusion plasmas, radiation damage to biological tissues and more. A radical update of the previous expert system for computing observables relevant to these processes, Quantemol-N, is presented. The new Quantemol Electron Collision (QEC) expert system simplifyies the user experience, improving reliability and implements new features. The QEC GUI interfaces the Molpro quantum chemistry package for molecular target setups and to the sophisticated UKRmol+ codes to generate accurate and reliable cross-sections. These include elastic cross-sections, super elastic cross-sections between excited states, electron impact dissociation, scattering reaction rates, dissociative electron attachment, differential cross-sections, momentum transfer cross-sections, ionization cross sections and high energy electron scattering cross-sections. With this new interface we will be implementing dissociative recombination estimations, vibrational excitations for neutrals and ions, and effective core potentials in the near future.

Blood Concentrates (BCs) are autologous non-transfusional therapeutical preparations with biological properties applied in tissue regeneration. These BCs differ in the preparation method, in fibrin network architecture, growth factors release as well as in platelet/cell content. Methodological changes result in distinct matrices that can compromise their clinical effectiveness. The present study evaluated the influence of different g-forces and types of tubes in the release of vascular endothelial growth factor (VEGF) from platelet-rich fibrin (PRF) as a function of time. The PRF-like samples were obtained with three g-forces (200, 400, and 800 x g) for 10 minutes in pure glass tubes or in polystyrene-clot activator tubes. Scanning and Transmission electron microscopy was used to morphometric analyzes of PRF’s specimens and flow cytometry was used to quantify VEGF slow release until 7 days. Our results showed that platelets were intact and adhered to the fibrin network, emitting pseudopods and in degranulation. The fibrin network was rough and twisted with exosomic granulations impregnated on its surface. An increase in the concentration of VEGF in the PRF supernatant was observed until 7 days for all g forces (200, 400 or 800 x g), with the highest concentrations observed with 200 x g, in both tubes, glass or plastic. Morphological analyzes showed a reduction in the diameter of the PRF fibers after 7 days. Our results showed that g-force interferes with the shape of the fibrin network in the PRF, as well as affect the release of VEGF stored into platelets. This finding may be useful in applying PRF to skin lesions, in which the rapid release of growth factors can favor the tissue repair process. Our observations point to a greater clarification on the methodological variations related to obtaining PRF matrices, as they can generate products with different characteristics and degrees of effectiveness in specific applications.

Enamel matrix derivative (EMD) is used for periodontal tissue regeneration therapy, and can induce mineralization in dental pulp cells (DPCs). We designed a synthetic peptide (SP) derived from the response of cells to EMD, and investigated the effect of the SP on potentiating osteogenesis in DPCs, which have a critical role of dental pulp homeostasis. DPCs were treated with 0, 10, 100, or 1000 ng/mL SP to determine its effect on cell proliferation, cell migration, cell differentiation, and mineralization. We then examined the molecular effects of the SP, focusing on changes in the mitogen-activated protein kinases (MAPK) signaling pathway in these cells. The SP significantly promoted DPC proliferation and migration. Cultures treated with the SP also showed an enhanced expression of markers of osteogenic differentiation and mineralization. The SP also induced the activation of MAPK signaling pathway components. These results suggest that our SP could promote the dental pulp tissue repair by hard tissue formation and the mineralization through activating MAPK signaling pathway. This study provides the first evidence that SP might be a new material for dental pulp tissue treatment.

In this article, bio-composites derived from starch-glycerol biodegradable matrix reinforced with jute fibers have been fabricated using the wet hand lay-up and compression moulding techniques. Samples having different weight percentages of jute fiber in the starch matrix have been analysed. The fibers surface was chemically treated by alkaline sodium hydroxide for improving the interphase bonding between fiber and matrix. Tensile test for the composites were done and the sample with highest tensile strength was selected for further tests that included water absorption, scanning electron microscopy and thermal analysis. It has been concluded that the ultimate tensile strength was found to be maximum for the composition of 15% fiber by weight composite as 7.547 MPa without epoxy coating and 10.43 MPa with epoxy coating. The major disadvantage of bio-composite is its high water absorption property, which in this study has been inhibited by the epoxy resin layer. Herein, the results of various tests done disclose a noteworthy improvement in the overall properties of bio-composite, in comparison to the neat biodegradable starch matrix.

Different organisms, cell types, and even similar cell lines can dramatically differ in resistance to genotoxic stress. This testifies to the wide opportunities for genetic and epigenetic regulation of stress resistance. These opportunities could be used to increas the effectiveness of cancer therapy, develop new varieties of plants and animals, and search for new pharmacological targets to enhance human radioresistance, for example, for -manned deep space expeditions. Based on the comparison of transcriptomic studies in cancer cells, in this review we propose that there is a high diversity of genetic mechanisms of development of genotoxic stress resistance. This review focused onpossibilities and limitations of the proposed regulation of the resistance of normal cells whole organisms to genotoxic and oxidative stress by overexpressing of stress-response genes. Moreover, the existing experimental data on the effect of such overexpression on the resistance of cells and organisms to various genotoxic agents has been analyzed and systematized. We suggest that the recent advances in the development of multiplex and highly customizable gene overexpression technology that utilizes the mutant Cas9 protein and the wealth of available data on gene functions and their signal networks open new opportunities for research in this field.

Objective: Regeneration of bone defects remains a challenge for maxillofacial and reparative surgeons. The purpose of this histological study was to assess the osteogenic potential of octacalcium phosphate (OCP) and bone matrix gelatin (BMG) alone and in combination in artificially created mandibular bone defects in rats. The quality of the newly formed bone was also evaluated. Methods: Thirty-six male Sprague Dawley rats (6-8 weeks old with 120-150 g weight) were randomly divided into four groups. Defects (3 mm in diameter and 2 mm in depth) were created in the mandible of rats and filled with 6 mg of OCP, BMG or a combination of both (1/4 ratio), respectively. Defects were left unfilled in the control group. To assess osteoinduction and bone regeneration and determine the quality of the newly formed bone, tissue specimens were harvested at seven, 14, and 21 days post-implantation. The specimens were processed, stained with hematoxylin and eosin (H&E) and histologically analyzed under light microscopy. Results: In the experimental groups, new bone formation was initiated at the margins of defects from seventh day after implantation. At the end of the study period, the amount of the newly formed bone increased and the bone was relatively mature. Osteoinduction and new bone formation were greater in OCP/BMG group. In the control group, slight amount of new bone had been formed at the defect margins (next to host bone) on day 21. Conclusion: Combination of OCP/BMG may serve as an optimal biomaterial for treatment of mandibular bone defects.

Aflatoxins, which have been classified as a group-1 carcinogen are the well-known mycotoxins produced by Aspergillus flavus. Aflatoxins have been linked to liver diseases, acute hepatic necrosis, resulting in cirrhosis or hepatocellular carcinomas due to which it incurs a loss of value in international trade for peanuts contaminated with it. The four main aflatoxins are B1, B2, G1, and G2 of which B1 is predominant. In plants, the cell wall is the primary barrier against pathogen invasion. Cell wall fortifications such as deposition of callose, cellulose, lignin, phenolic compounds and structural proteins help to prevent the pathogen infection. Further, the host cell’s ability to rapidly repair and reinforce its cell walls will result in a reduction of the penetration efficiency of the pathogen. Peanut seed coat acts as a physical and biochemical cell wall barrier against both pre and post-harvest pathogen infection. The structure of seed coat and the presence of polyphenol compounds have been reported to inhibit the growth of A. flavus, however, not successfully employed to develop A. flavus resistance in peanut. A comprehensive understanding of peanut seed coat development and biochemistry will provide information to design efficient strategies for the seed coat mediated A. flavus resistance and Aflatoxin contamination.

Microscale surgery on single cells and small organisms have enabled major advances in fundamental biology and in engineering biological systems. Examples of applications range from wound healing and regeneration studies to the generation of hybridoma to produce monoclonal antibodies. Even today, these surgical operations are often performed manually, but they are labor-intensive and lack reproducibility. Microfluidics has emerged as a powerful technology to control and manipulate cells and multicellular systems at the micro- and nanoscale with high precision. Here, we review the physical and chemical mechanisms of microscale surgery, and the corresponding design principles, applications, and implementations in microfluidic systems. We consider four types of surgical operations: 1) Sectioning, which splits a biological entity into multiple parts, 2) ablation, which destroys part of an entity, 3) biopsy, which extracts materials from within a living cell, and 4) fusion, which joins multiple entities into one. For each type of surgery, we summarize the motivating applications and the microfluidic devices developed. Throughout the review, we highlight existing challenges and opportunities. We hope that this review will inspire scientists and engineers to continue to explore and improve microfluidic surgical methods.

Hospital-based programs democratize mRNA therapeutics by facilitating the processes to translate a novel RNA idea from the bench to the clinic. Because mRNA is essentially biological software, therapeutic RNA constructs can be rapidly developed. The generation of small batches of clinical grade mRNA to support IND applications and first-in-man clinical trials, as well as personalized mRNA therapeutics delivered at the point-of-care, is feasible at a modest scale of cGMP manufacturing. Advances in mRNA manufacturing science and innovations in mRNA biology, are increasing the scope of mRNA clinical applications.

MAPLE (matrix assisted pulsed laser evaporation) depositions of Candida Rugosa lipase were carried out from ice matrices whose composition is optimized in order to minimize conformational damage of the protein, which strongly influences its catalytic activity. To induce lid opening and to protect lipase during the MAPLE process, pentane and m-DOPA amino acid were added to the liquid matrix giving a target formed by a frozen water-lipase-pentane microemulsion. FTIR and AFM were used to investigate the structure of MAPLE deposited lipase films. The ability of MAPLE films to promote transesterification was determined by thin layer chromatography. It was shown that m-DOPA has influence on the aggregation but not on the unfolding of lipase induced by MAPLE, while the microemulsion formed by the addition of pentane to the target composition is effective in protecting lipase during the MAPLE process. MAPLE deposited lipases showed a modified specificity.

This study aimed to investigate Coll-I, III, IV and elastin in canine normal prostate and PC, using Picrosirius red (PSR) and Immunohistochemical (IHC) analysis. Eight normal prostates and 10 PC from formalin-fixed, paraffin-embedded samples were used. Collagen fibers area was analyzed with ImageJ software. The distribution of Coll-I and Coll-III was approximately 80% around prostatic ducts and acini, 15% among smooth muscle and 5% surrounding blood vessels, in both normal prostate and PC. There was a higher median area of Coll-III in PC, when compared to normal prostatic tissue (p=0.001 for PSR and p= 0.05 for IHC). Immunostaining for Coll-IV was observed in the basal membrane of prostate acini, smooth muscle, blood vessels, and nerve fibers of normal and PC samples. Although there was no difference in Coll-IV area between normal tissue and PC, tumors with Gleason score 10 showed absence of Coll-IV, when compared to scores 6 and 8 (p=0.0095). Elastic fibers were found in the septa dividing the lobules and around the prostatic acini of normal samples, and was statistically higher in PC, compared to normal tissue (p=0.00229). Investigation of ECM components brings new information and should be correlated with prognosis in future studies.

Cachexia is a complex metabolic syndrome characterized by loss of skeletal muscle, leading to a significant weight loss that impacts patient morbidity and mortality. Given the complexity of gene regulatory networks that control gene expression, our objective was to perform an integrative mRNA and miRNA profiling to identify genetic programs that capture essential mechanistic details that promote muscle atrophy in cancer cachexia. Here, we used RNA sequencing to analyze miRNAs and mRNAs expression profiles in tibialis anterior (TA) muscles of the Lewis lung carcinoma model of cancer cachexia. In addition, we compared these findings with RNA-Seq data from C2C12 myotubes treated in vitro with the cachectic factors tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Extracellular matrix (ECM) alterations were validated by picrosirius staining, western blot, and fractal dimension analyses. We found 1,008 mRNAs and 18 miRNAs differentially expressed in cachectic mice. This set of genes was associated with the ECM, proteolysis, and inflammatory response. Enrichment analysis of transcriptional factor binding sites revealed activation of the atrophy-related transcriptional factors: NF-κB, Stat3, AP-1, and FoxO. Furthermore, the integration of mRNA and miRNA expression profiles identified post-transcriptional regulation by miRNAs of genes involved in ECM organization, cell migration, transcription factors binding, ion transport, and FoxO signaling pathway. C2C12 myotubes treated with TNF-α and IFN-γ similarly down-regulate subsets of ECM genes, including collagens. Our integrative analysis of miRNA-mRNA co-profiles comprehensive characterized regulatory relationships of molecular pathways and revealed miRNAs targeting ECM-associated genes in cancer cachexia. We also confirmed in C2C12 myotubes that changes in ECM-associated genes are dependent on inflammatory signaling of the cytokines TNF-α and IFN-γ.

The CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that regulates cellular proliferation, differentiation, apoptosis and tumorigenesis. Although the pro-oncogenic roles of C/EBPβ have been implicated in various human cancers, how it contributes to tumorigenesis or tumor progression has not been determined. Immunohistochemistry with human non-small cell lung cancer (NSCLC) tissues revealed that higher levels of C/EBPβ protein are expressed compared to normal lung tissues. Knockdown of C/EBPβ by siRNA reduced the proliferative capacity of NSCLC cells by delaying G₂/M transition of the cell cycle. In C/EBPβ-knockdown cells, a prolonged increase in phosphorylation of cyclin dependent kinase 1 at tyrosine 15 (Y15-pCDK1) was displayed with increased Wee1 and decreased Cdc25B expression, simultaneously. ChIP analysis showed that C/EBPβ bound to distal promoter regions of WEE1 and repressed WEE1 transcription through the interaction with histone deacetylase 2. Treatment of C/EBPβ-knockdown cells with a Wee1 inhibitor induced a decrease in Y15-pCDK1 and recovered cells from G₂/M arrest. In the xenograft tumors, the depletion of C/EBPβ significantly reduced tumor growth. Taken together, these results indicate that Wee1 is a novel transcription target of C/EBPβ that is required for the G₂/M phase of cell cycle progression, ultimately regulating proliferation of NSCLC cells.

The major auxin, indole-3-acetic acid (IAA), is associated with a plethora of growth and developmental processes including embryo development, expansion growth, cambial activity, and the induction of lateral root growth. Accumulation of the auxin precursor indole-3-acetamide (IAM) induces stress related processes by stimulating abscisic acid (ABA) biosynthesis. How IAM signaling is controlled is, at present, unclear. Here, we characterize an ami1/rooty double mutant, that we initially generated to study the metabolic and phenotypic consequences of a genetic blockade of the indole glucosinolate and IAM pathways in Arabidopsis thaliana. Our mass spectrometric analyses of the mutant revealed that the combination of the two mutations is not sufficient to fully prevent the conversion of IAM to IAA. The detected strong accumulation of IAM was, however, recognized to substantially impair seed development. We further show by genome-wide expression studies that the double mutant is broadly affected in its translational capacity, and that a small number of cell proliferation and plant growth regulating transcriptional circuits are repressed by the high IAM content in the seed. In accordance with the previously described growth reduction in response to elevated IAM levels, our data support the hypothesis that IAM is a growth repressing counterpart to IAA.

Information molecules of DNA and RNA should obey principles of quantum mechanics where unitary operators in form of unitary matrices have key meanings. Unitary matrices are the basis of calculations in quantum computers. This article presents some author's results, which show that matrix forms of the representation of structured systems of molecular-genetic alphabets can be considered as sets of sparse unitary matrices related with phenomenologic features of the degeneracy of the genetic code. These sparse unitary matrices have orthogonal systems of functions in their rows and columns. A complementarity exists among some unitary genetic matrices in relation each other. Decompositions of numeric genetic matrices into sets of sparse unitary matrices are connected with the logical operation of modulo-2 addition used in quantum computers as well. Tensor (or Kronecker) families of unitary genetic matrices with their fractal-like properties are also considered. The described results are discussed in the frame of development of quantum-information approaches for modeling genetic systems.

Cancer is a leading cause of death worldwide. It is theorized that underlying genetic and epigenetic changes enable cells to proliferate out of control by escaping regulatory mechanisms. The progression of cancer is associated with increased cell proliferation, metabolic modifications, resistance to apoptosis, genetic instability, induction of angiogenesis and augmented migratory capability. Recent developments in DNA and RNA analysis have made it possible to study these genetic changes systematically. These advances have enabled us to possess a deeper knowledge of the signaling pathways and involved processes. In-depth studies of the pathways involved in carcinogenesis have led to the identification of pathways that may be targeted for therapeutic purposes. In this review, we provide an overview of the relevant mechanisms and pathways involved in the development and progression of cancer.

Purpose: Myelodysplastic syndromes (MDS) are caused by a stem cell failure, but the relationship between immune dysregulation and the course of disease has not yet been analyzed in detail. Experimental design: To get insights into the pathophysiologic and clinical relevance of the histotopography of immune cell subpopulations in this process, the immune cell infiltrate with focus on its spatial distribution was determined by multispectral imaging (MSI) in 147 bone marrow biopsies from MDS or secondary acute myeloid leukemia (sAML) patients and healthy controls (HC). In addition, the data were correlated to genetic alterations and clinical features of these patients including therapy response. Results: A high inter-tumoral heterogeneity in the frequency and spatial distribution of CD3⁺CD8⁺, CD3⁺CD8^-, CD3⁺FOXP3⁺ T cell subsets, MUM1p⁺CD3^- post-germinal B/plasma cells and CD34⁺ blasts was found in MDS and sAML samples. In HC only few B cells/plasma cells, but no T cell subpopulations were detected in the proximity to CD34⁺ blasts. In contrast, the frequency of these lymphocytes was increased in proximity to CD34⁺ blasts in both MDS and sAML independent of the karyotype, genetic alterations frequently detected in MDS, clinical risk stratification systems or treatment response to hypomethylating agents. Furthermore, an increased frequency of CD3⁺CD8⁺ T cells and MUM1p⁺ CD3^- B cells was found in responders to epigenetic drugs. Conclusions: Thus, we conclude that (i) T cell subsets do not belong to the normal stem cell niche, (ii) the presence of T and B cell subpopulations not directly affect the course of MDS, (iii) lymphocytes in the proximity to CD34⁺ blasts might indicate defective stem cell properties and (iv) the number of lymphocytes is a predictor of therapy response to hypomethylating agents.

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

To improve the interfacial bonding of sisal fiber reinforced polylactide biocomposites, polylactide (PLA) and sisal fibers (SF) were melt-blended to fabricate bio-based composites via in situ reactive interfacial compatibilization with the addition of an epoxy-functionalized oligomer (ADR). The FTIR analysis and SEM characterization demonstrated that PLA molecular chain was bonded to the fiber surface and epoxy-functionalized oligomer played a hinge-like role between sisal fibers and PLA matrix, which resulted in improved interfacial adhesion between fibers and PLA matrix. The interfacial reaction and microstructures of composites were further investigated by thermal and rheological analyses, which indicated that the mobility of the PLA molecular chain in composites was restricted because of the introduction of ADR oligomer, which in turn reflected the improved interfacial interaction between SF and PLA matrix. These conclusions were further investigated by the calculated activation energies of glass transition relaxation (△Ea) of composites via dynamic mechanical analysis. The mechanical properties of PLA/SF composites were simultaneously reinforced and toughened via addition of ADR oligomer. The interfacial interaction and structure-properties relationship of composites are key points of this study.

There are many species of endemic plants from Mexico, without food or commercial use, but with different applications in traditional medicine and valuable for their content of secondary metabolites. In this sense, we found two species of Cucurbitacea family plants natives of southeast and gulf of México, with traditionally use how soap and laundry agent, control of some pests, and it has also been used how infusion for the treatment of different types of dermatitis and stomachache. In the present work, we evaluate the antiproliferative activity in vitro, of six crude organic extracts, tested against six human tumor cell lines, A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast) and WiDr (colon), the results indicated that at least three extracts from both species presents an interesting antiproliferative activity on five tumor cell lines.

Typhonium flagelliforme is an Indonesian herbal plant used and applied traditionally to treat cancer diseases. Gamma rays have irradiated rodent tuber mutant plant at six doses gray to in-crease the chemical compounds of anticancer activity. The effect of isolated compounds from ro-dent tuber mutant plants has never been studied and published yet. Our study unveiled the poten-tial of stigmasterol as a remarkable cytotoxic agent and the significant contribution of NMR spectroscopy, IR, Mass spectra, QTOF MS towards the isolation and identification of this anti-cancer agent. Stigmasterol was isolated from T. flagelliforme mutant plant. Stigmasterol was more effective against MCF-7 cells with an IC50 value of 0.1623 µM than Cisplatin with IC50 value 13.2 µM. It is the most potential and active fraction in the human breast cancer cell line. The mo-lecular docking study analyzed the chemical profile of stigmasterol to confirm the receptor in agonist binding sites. The prediction of the toxicity of stigmasterol compounds using in silico and analysis of its interaction with the receptor can act as a competitive regulator with a high-affinity binding site on FXR. Stigmasterol has potential as a candidate for an anticancer drug that pro-moting further clinical action.

Photoelectrochemical water splitting is a promising field for sustainable energy production using hydrogen. Development of efficient catalysts is essential for resourceful hydrogen production. The most efficient catalysts reported to date have been extremely precious rare-earth metals. One of the biggest hurdles in this research area is the difficulty of developing highly efficient catalysts comparable to the noble metal catalysts. Here, we report that non-noble metal dichalcogenide (Co₃Se₄) catalysts made using a facile one-pot electrodeposition method, showed highly efficient photoelectrochemical activity on a Si photocathode. To enhance light collection and enlarge its surface area even further, we implemented surface nano-structuring on the Si surface. The nano-structured Si photoelectrode has an effective area greater than that of planar silicon and a wider absorption spectrum. Consequently, this approach exhibits reduced overvoltage as well as increased photo-catalytic activity. Such results show the importance of controlling the optimized interface between the surface structure of the photoelectrode and the electrodeposited co-catalyst on it to improve catalytic activity. This should enable other electrochemical reactions in a variety of energy conversion systems.

The wide range of applications of nanoparticles (NPs) has increased the probability of environmental and occupational exposure. In a previous comparative study on cell line A549, we observed that oxidative stress caused by Co₃O₄ NPs affects the energetic homeostasis and the detoxification capacity, preventing autophagy induced by TiO₂ NPs. In this study, we have investigated the effects of NPs on the cell cycle.Cytofluorimetric analysis showed a slow-down of the cell cycle progression for both NPs, with increases in the percentage of resting cells in the G0/G1. These observations were confirmed by a reduced expression of all cyclins, especially of CCNE1 and CDK2, involved in the late stages of the G1 phase, coupled with a significant increase in the expression of p21 only for Co₃O₄ NP exposure. On the contrary, the effects of TiO₂ NPs were modest. Cell cycle related miRNA-34a, miRNA-126 and miRNA-1290 resulted increased at different early time-points (4-8h) but were down-expressed at 24h-48h only after TiO₂ NP exposure. Our results show that NPs have an antiproliferative effect and deregulate cell cycle on A549 cells. These effects should not be underestimated because regulation of cycle progression is crucial for cell survival and repair of genetic damage.

Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its copy number alteration (CNA) and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2 and 12p13.31 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.

The feasibility of using full ion kinetics, instead of gyrokinetics, in simulating low-frequency Ion-Temperature-Gradient (ITG) instabilities in tokamaks has recently been demonstrated by Sturdevant et al. [Physics of Plasmas 24, 081207 (2017)]. In that work, a variational integrator was developed to integrate the full orbits of ions in toroidal geometry, which proved to be accurate in capturing both the short-time scale cyclotron motion and long time scale drift motion. The present work extends that work in three aspects. First, we implement a relatively simple full orbit integrator, the Boris integrator, and demonstrate that the accuracy of this integrator is also sufficient for simulation of ITG instabilities. Second, the equilibrium magnetic configuration is extended to general toroidal configuration specified numerically, enabling simulation of realistic equilibria reconstructed from tokamak experiments. Third, we extend that work to the nonlinear regime and investigate the nonlinear saturation of ITG instabilities. To verify the new numerical implementation of the orbit integrator and magnetic configuration, the linear electrostatic ITG frequency and growth rate are compared with those given in Sturdevant's work and good agreement is found.

Engineering of drug nanocarriers combining fine-tuned mucoadhesive/mucopenetrating properties is currently being investigated to ensure more efficient mucosal drug delivery. Aiming to improve the transmucosal delivery of hydrophobic drugs, we designed a novel kind nanogel produced by the self-assembly of amphiphilic chitosan graft copolymers ionotropically crosslinked with sodium tripolyphosphate. In this work, we synthesized for the first time chitosan-g-poly(methyl methacrylate) nanoparticles thiolated by the conjugation of N-acetyl cysteine. First, we confirmed that both non-crosslinked and crosslinked nanoparticles in the 0.05-0.1% w/v concentration range display very good cell compatibility in two cell lines that are relevant to oral delivery, Caco2 cells that mimic the intestinal epithelium and HT29-MTX cells that produce mucin. Then, we evaluated the effect of crosslinking, nanoparticle concentration and thiolation on the permeability in vitro utilizing monolayers of (i) Caco2 and (ii) Caco2:HT29-MTX cells (9:1 cell number ratio). Results confirmed that the ability of the nanoparticles to cross Caco2 monolayer was affected by the crosslinking. In addition, thiolated nanoparticles interact more strongly with mucin, resulting in a decrease of the apparent permeability coefficient (Papp) compared to the pristine nanoparticles. Moreover, for all the nanoparticles, higher concentration resulted in lower Papp suggesting indicating that the transport pathways could undergo saturation.

A novel stationary phase for affinity separations is presented. This material is based on sintered borosilicate glass readily available as semi-finished filter plates with defined porosity and surface area. The material shows fast binding kinetics and excellent long-term stability under real application conditions due to lacking macropores and high mechanical rigidity. The glass surface can be easily modified with standard organosilane chemistry to immobilize selective binders or other molecules used for biointeraction. In this paper, the manufacturing of the columns and their respective column holders by 3D printing is shown in detail. The model system protein A/IgG was chosen as an example to examine the properties of such monolithic columns under realistic application conditions. Several specifications, such as (dynamic) IgG capacity, pressure stability, long-term performance, productivity, non-specific binding, and peak shape, are presented. It could be shown that due to the very high separation speed, 250 mg antibody per hour and column can be collected, which surpasses the productivity of most standard columns of the same size. The total IgG capacity of the shown columns is around 4 mg (5.5 mg/mL), which is sufficient for most tasks in research laboratories. The cycle time of an IgG separation can be less than 1 minute. Due to the glass material's excellent pressure resistance, these columns are compatible with standard HPLC systems. This is usually not the case with standard affinity columns, limited to manual use or application in low-pressure systems. The use of a standard HPLC system also improves the ability for automation, which enables the purification of hundreds of cell supernatants in one day. The sharp peak shape of the elution leads to an enrichment effect, which might increase the concentration of IgG by a factor of 3. The final concentration of IgG can be around 7.5 mg/mL without the need for an additional nanofiltration step. The purity of the IgG was > 95% in one step and nearly 99% with a second polishing run.

Plasma medicine is a new field focusing on biomedical and clinical applications of cold physical plasmas, including their anticancer effects. Cold plasmas can be applied directly or indirectly as plasma activated liquids (PAL). The effect of plasma activated cell growth medium (PAM) and plasma activated phosphate buffered saline (PAPBS) were tested using a plasma pen generating streamer corona discharge in ambient air, on different cancer cell lines (melanoma A375, glioblastoma LN229 and pancreatic cancer MiaPaCa-2) and normal cells (human dermal fibroblasts HDFa). The viability reduction and apoptosis induction were detected in all cancer cells after incubation in PAL. In melanoma cells we focused on detailed insights to the apoptotic pathways. The anticancer effects depend on the plasma treatment time or PAL concentration. The first 30 minutes of incubation in PAL were enough to start processes leading to the cell death. In fibroblasts, no apoptosis induction was observed, only PAPBS, activated for longer time, slightly decreased their viability. Anticancer effects of PAM and PAPBS on cancer cells showed selectivity compared to normal fibroblasts, depended on correctly chosen activation time and PAL concentration. This selectivity, supported by optimum ratio of hydrogen peroxide and nitrites in PAL, is very promising for potential clinical applications.

Multiple unique environmental factors such as space radiation and microgravity (µG) pose a serious threat to human gene stability during space travel. Recently, we reported that simultaneous exposure of human fibroblasts to simulated µG and radiation results in more chromosomal aberrations than in cells exposed to radiation alone. However, the mechanisms behind this remain unknown. The purpose of this study was thus to obtain comprehensive data on gene expression using a 3D clinostat synchronized to a carbon (C)-ion or X-ray irradiation system. Human fibroblasts (1BR-hTERT) were maintained under standing or rotating conditions for 3 or 24 h after synchronized C-ion or X-ray irradiation at 1 Gy as part of a total culture time of 2 days. Among 57,773 genes analyzed with RNA sequencing, we focused particularly on the expression of 82 cell cycle-related genes after exposure to the radiation and simulated µG. The expression of cell cycle-suppressing genes (ABL1 and CDKN1A) decreased and that of cell cycle-promoting genes (MKI67, KPNA2, CCNB1, STMN1, and MCM4) increased after C-ion irradiation under µG. The cell cycle may pass through the G1/S and G2 checkpoints with DNA damage due to the combined effects of C-ions and µG, suggesting that increased genomic instability might occur in space.

The recent Zika virus (ZIKV) outbreak in Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies and Guillain-Barré syndrome. In responding to this global health outcry, unprecedented and world-wide efforts are taking place to study the ZIKV etiology. Much have been learned about this virus in the areas of epidemiology, clinical manifestation, viral sequences and protein structures, as well as effects of ZIKV infection on fetal brain development and microcephaly. However, the molecular mechanism underlying ZIKV-mediated neurologic disorders remains elusive. Some critical questions include: 1) what type of virologic changes has taken place that increased the viral virulence? 2) which ZIKV protein(s) is responsible for the enhanced viral pathogenicity? And 3) how the newly adapted and pathogenic ZIKV strains alter their interactions with host cells leading to neurologic disorders? The goal of this review is to explore the molecular insights into the ZIKV-host interactions with special focuses on host cell receptor usage for viral entry, host cellular and immune antiviral responses, ZIKV counteraction and ZIKV-induced cytopathic effects. Our hope with this literature review is to inspire additional studies focusing on molecular studies of ZIKV-host Interactions.

Recently, we have witnessed a booming development of composites and multi-dopant metal oxides to be employed as novel photocatalysts. Yet the practical application of photocatalysis for environmental purposes is still elusive. Concerns about the unknown fate and toxicity of nanoparticles, unsatisfactory performance in real conditions, mass transfer limitations and durability issues have so far discouraged investments in full-scale applications of photocatalysis. Herein, we provide a critical overview of the main challenges that are limiting large-scale application of photocatalysis in air and water/wastewater purification. We then discuss the main approaches reported in the literature to tackle these shortcomings, such as the design of photocatalytic reactors that retain the photocatalyst, the study of degradation of micropollutants in different water matrices, and the development of gas-phase reactors with optimized contact time and irradiation. Furthermore, we provide a critical analysis of research-practice gaps such as treatment of real water and air samples, degradation of pollutants with actual environmental concentrations, photocatalyst deactivation, and cost and environmental life-cycle assessment.

The investigation of the electromagnetic properties of biological particles in microfluidic platforms may enable wireless monitoring and interaction with functional activity of microorganisms. Of high relevance is the membrane potential as it is one of the most important parameters of living cells. In particular, the complex mechanisms of the cell’s membrane potential are comparable to the dynamics of bacteria membranes, providing a simplified platform for advancing the current techniques and knowledge of general bio-particle dynamics. In this work, we provide a theoretical analysis and experimental results on the microwave detection of bacteria on a microfluidic-based framework for sensing the membrane potential of bacteria. The results enable to further advance the state-of-the-art of electromagnetic bacteria sensing and microfluidic control, and their implication for measuring and interacting with the cell and its membrane potentials, which is of great importance for developing new biotechnological engineered systems and solutions.

It is shown that a Mueller quaternion can be formulated as a quaternion with matrix coefficients, and this Mueller quaternion transforms the Stokes quaternion for depolarizing process as well as for nondepolarizing process. Mueller quaternion keeps track of the phase acquired by the Stokes quaternion and, in general, quaternion states of optical media comprises all properties of Jones, Mueller-Jones and Mueller matrices.

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders. In order to replace the function of the destroyed pancreatic beta cells in diabetes, islet transplantation is the widely practiced treatment; however, it has several limitations. As an alternative approach, human pluripotent stem cells (hPSCs) can provide an unlimited source of pancreatic cells that have the ability to secrete insulin in response to high blood glucose level. However, determination of the appropriate pancreatic lineage candidate for the purpose of cell therapy for treatment of diabetes is still debated upon. While hPSC-derived beta cells are perceived as the ultimate candidate, the efficiency needs further improvement in order to obtain a sufficient number of glucose responsive β-cells for transplantation therapy. On the other hand, hPSC-derived pancreatic progenitors can be efficiently generated in vitro and can further mature into glucose responsive beta cells in vivo after transplantation. Herein, we discuss the advantages and predicted challenges associated with the use of each of the two pancreatic lineage products for diabetes cell therapy. Furthermore, we address co-generation of functionally relevant islet cell subpopulations and structural properties contributing to glucose responsiveness of beta cells, as well as the available encapsulation technology for these cells.

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

The CRISPR/Cas9 gene editing system has enormous potential in the treatment of multiple genetic disorders. To fully harness this potential, it is essential to deliver CRISPR-Cas9 components safely and effectively into the nuclei of target cells. In this study, we tested the amphipathic cell-penetrating peptide LAH5, previously used for DNA delivery, to intracellularly deliver spCas9: sgRNA ribonucleoprotein (RNP) and RNP/single-stranded homology-directed repair (HDR) template. We discovered that the LAH5 peptide effectively formed nanocomplexes with both RNP and RNP/HDR cargo, and that these nanocomplexes were taken up by cells effectively. Peptide/RNP nanocomplexes were characterized for size and charge, and nanocomplexation with RNP and RNP/HDR cargo was demonstrated via an electrophoretic mobility shift assay. Various ratios of peptide/RNP nanocomplexes were functionally screened on fluorescent reporter cell lines for gene editing and HDR-mediated gene correction. Additionally, targeted gene editing of the CCR5 gene was demonstrated in various cell lines. This LAH5-based delivery strategy paves the way for the development of therapeutic delivery systems for CRISPR/Cas-based genomic engineering.

Cell death resistance is a key feature of tumor cells. One of the main anti-cancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD). It has been suggested that ICD inducers are two different types according to their various activities. Here, we review the well-characterized DAMPs and focus on the different types of ICD inducers and recent combination therapies that can augment the immunogenicity of cancer cells.

Complete pathologic response (pCR) predicts the long-term outcome of neoadjuvant treated (NAC) breast cancer (BC) but is reached in <10% of hormone-receptor-positive patients. Biomarkers able to guide adjustment or interruption of an ineffective therapy are desired. Here, we evaluated whether shifts in the serum concentration of thymidine kinase 1 (sTK1) during NAC could be utilized as a biomarker. In the PROMIX trial, women with localized HER2- BC received neoadjuvant epirubicin/docetaxel in six cycles. sTK1 was measured with an ELISA in 54 patients at cycles 1-4 and in a total of 131 patients before and 48h after cycle 1. The prognostic significance of the results was evaluated by log-rank tests of Kaplan–Meier estimates. Treatment resulted in a 2-fold increase of sTK1 before and 3-fold increase 48h after the cycles, except for the first cycle, where half of patients reacted with a decrease (post/pre sTK1- ratio <1.12) and the other half reacted with an increase (ratio >1.12). OS rates in ER+ patients with ratios of >1.12 and <1.12 were 97.7% and 78% (p=0.005), respectively, and DFS rates were 90.7% and 68% (p=0.006), respectively. Thus, response of sTK1 at the first cycle of chemotherapy could be used both as an early biomarker for guidance of chemotherapy and for the study of inherent tumor chemo-sensitivity, which could predict long-term outcome prior to therapy.

This work evaluates the surface water quality in terms of physico-chemical parameters of the Brahmani River, Odisha using statistical analysis involving the calculation of correlation coefficient and regression equation. Besides this, the work also highlights and draws attention towards the “Water Quality Index” in a simplified format which may be used at large and could represent the reliable picture of water quality. Surface water quality data is taken from OSPCB of various location i.e. Panposh D/S, Rourkela D/S, Rengali, Talcher U/S, Kamalanga D/S, Bhuban, Pattamundai and was assessed for summer, monsoon, winter for the years 2011, 2012, 2013, 2014 and 2015. Average of values, minimum of values and maximum of values of water quality parameters were obtained seasonally over the above mentioned years. Besides this, the standard deviation for the water quality parameters was also obtained for water quality parameters namely pH, Temperature, DO, TDS, Alkalinity, EC, Na+, Ca2+, Mg2+, K+, F-, Cl-, NO3-, SO42- and PO42-. Seasonal changes in various physical and chemical parameters were analysed.The values obtained were compared with the guideline values for drinking water by Bureau of Indian Standard (BIS). A systematic correlation and regression study is carried out for three seasons, showed linear relationship among different water quality parameters. This provides an easy and rapid method of monitoring water quality. Highly significant (0.8< r <1.0), moderately significant (0.6< r <0.8) and significant (0.5< r <0.6) correlations between the parameters have been worked out. High correlation coefficient has been observed between TDS,EC-Na+, Ca2+, Cl-, SO42- ; Na+- Cl-. From the collected quantities, certain parameters were selected to derive WQI for the variations in water quality of each designated sampling site. WQI of Brahmani River ranged from 36.7 to 44.1 which falls in the range of good quality of water.Panposh D/S and Rourkela D/S showed poor water quality in summer and winter season. It is shown that WQI may be a useful tool for assessing water quality and predicting trend of variation in water quality at differentlocations in the Brahmani River.

Nonhost disease resistance is the most common type of plant defense mechanism against potential pathogens. In this study, the metabolic enzyme formate dehydrogenase (FDH1) was identified to be involved in nonhost disease resistance in Nicotiana benthamiana and Arabidopsis thaliana. In Arabidopsis, AtFDH1 was highly upregulated in response to both host and nonhost bacterial pathogens. Arabidopsis Atfdh1 mutants were compromised in nonhost resistance, basal resistance, and gene-for-gene resistance. The expression patterns of salicylic acid (SA) and jasmonic acid (JA) marker genes after pathogen infections in Atfdh1 mutant indicated that SA is most likely involved in the FDH1-mediated plant defense response to both host and nonhost bacterial pathogens. Previous studies reported that FDH1 localizes to only mitochondria, or both mitochondria and chloroplasts. Our results showed that the AtFDH1 localized to mitochondria and the amount of FDH1 localized to mitochondria increased upon infection with host or nonhost pathogens. Interestingly, the subcellular localization of FDH1 was observed in both mitochondria and chloroplasts after infection with a nonhost pathogen in Arabidopsis. We speculate that FDH1 plays a role in cellular signaling networks between mitochondria and chloroplasts to produce coordinated defense responses such as SA-induced reactive oxygen species (ROS) generation and hypersensitive response (HR)-induced cell death against nonhost bacterial pathogens.

Ongoing COVID-19 Pandemic has resulted into massive damage to various platforms of global economy which has caused disruption to human livelihood. Natural Language Processing has been extensively used in different organizations to categorize sentiments, perform recommendation, summarizing information and topic modelling. This research aims to understand the non-medical impact of COVID-19 on global economy by leveraging the natural language processing methodology. This methodology comprises of text classification which includes topic modelling on unstructured COVID-19 media articles dataset provided by Anacode. Like other Natural Language Processing algorithms, Latent Dirichlet allocation (LDA) and Non-negative matrix factorization (NMF) has been proposed to classify the media articles dataset in order to analyze COVID-19 pandemic impacts in the different sectors of global economy. Model Accuracy was examined based on the coherence and perplexity score which came out to be 0.51 and -10.90 using LDA algorithm. Both the LDA and NMF algorithm identified similar prevalent topics that was impacted by COVID-19 pandemic in multiple sectors of economy. Through intertopic distance map visualization produced by LDA algorithm, it can be reciprocated that general industries which includes children schooling, parental care, and family gatherings had the major impact followed by business sector and the financial industry.

Elite camels often suffer from massive injuries. Thus, there is a pivotal need for a cheap and readily available regenerative medicine source. We isolated novel stem-like cells from camel skin and investigated their multipotency and resistance against various stresses. Skin samples were isolated from ears of five camels. Fibroblasts, keratinocytes, and spheroid progenitors were extracted. After separation of different cell lines by trypsinization, all cell lines were exposed to heat shock. Then, fibroblasts and dermal cyst-forming cells were examined under cryopreservation. Dermal cyst-forming cells were evaluated for resistance against osmotic pressure. The results revealed that resistance periods against trypsin were 1.5, 4, and 7 minutes for fibroblasts, keratinocytes, and spheroid progenitors, respectively. Furthermore, complete recovery of different cell lines after heat shock along with the differentiation of spheroid progenitors into neurons was observed. Fibroblasts and spheroid progenitors retained cell proliferation after cryopreservation. Dermal cyst-forming cells regained their normal structure after collapsing by osmotic pressure. The spheroid progenitors incubated in the adipogenic, osteogenic, and neurogenic media differentiated into the adipocytes, osteoblasts, and neurons, respectively. To the best of our knowledge, we isolated different unique cellular differons and stem-like cells from the camel skin and examined their multipotency for the first time.

Fluorescent carbon dots (C-dots) were synthesized by one pot hydrothermal treatment of garlic juice at 180 °C for 7h. The as-prepared C-dots with an average diameter of 2.13±0.71 nm can be well dispersed, and show absinthe fluorescence with a quantum yield of 8.9% in water. The C-dots were fully characterized by TEM, XPS, XRD, and FTIR, respectively. Additionally, the as-prepared C-dots reveal nearly nontoxic to SW480 cells and can be used for cell imaging. The water solution of C-dots show sensitivity to pH values and metal ions, and also have a high selectivity to the Hg²⁺ ion among other transition metal ions, and achieve a high sensitive detection with the detection limit of 0.45 μM. The fluorescent C-dots are expected to be useful for the evaluation of mercury ions in environmental water system.

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of EdU⁺/αMHC-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP^high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP^low cells; however, S-phase synchronization didn’t enhance the polycistronic-MGT reprogramming, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF-5-FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the 1) induction of cell cycle arrest in the S phase and 2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both c-mesenchymal–epithelial transition (MET)/ Kirsten Rat Sarcoma virus (KRAS)/ extracellular signal-regulated kinase (ERK) and c-MET/ phosphatidyl-inositol 3-kinases (PI3K)/ protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/ matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required to validate the results of the present study.

Track-structure Monte Carlo simulations are useful tools to evaluate initial DNA damage induced by irradiation. In the previous study, we have developed a Gean4-DNA-based application to estimate the cell surviving fraction of V79 cells after irradiation, bridging the gap between the initial DNA damage and the DNA-rejoining kinetics by means of the two-lesion kinetics (TLK) model. However, since the DNA repair performance depends on cell line, the same model parameters cannot be used for the different cell lines. Thus, we extended the Geant4-DNA application with an updated TLK model for the evaluation of DNA damage repair performance in HSGc-C5 carcinoma cells which are typically used for evaluating proton/carbon radiation treatment effects. For this evaluation, we also performed experimental measurements for cell surviving fractions and DNA-rejoining kinetics of the HSGc-C5s cells. Concerning fast- and slow-DNA rejoining, the TLK model parameters were adequately optimized with the simulated initial DNA damage. Using the optimized TLK model, the Geant4-DNA simulation is now able to predict cell survival and DNA-rejoining kinetics for HSGc-C5s cells.

This paper proposes a novel model for a PV cell with parameters variance dependency on temperature and irradiance included. The model relies on commercial available data, calculates the cell parameters for standard conditions and then extrapolates them for the whole operating range. An up-to-date review of the PV modeling is also included with series and parallel parasitic resistance values and dependencies discussed. The parameters variance is analyzed and included in the proposed PV model, where the self-heating phenomenon is also considered. Each parameter variance is compared to the results from different authors. The model includes only standard components and can be run on any SPICE-based simulator. Unlike other approaches that consider the internal temperature as a parameter, our proposal relies on air temperature as an input and computes the actual internal temperature accordingly. Finally, the model is validated via experiments and comparisons to similar approaches are provided.

In fuel-cell technological development, one of the most important objectives is to minimize the amount of Pt, the most employed material as oxygen reduction and methanol oxidation electro-catalyst. In this paper we report the synthesis and characterization of Te nanotubes (TeNTs) decorated with Pt nanoparticles, readily prepared from stirred aqueous solutions of PtCl2 containing a suspension of TeNTs and ethanol acting as a reducing agent, avoiding the use of any hydrophobic surfactants as capping stabilizing substance. The as obtained TeNTs decorated with Pt nanoparticles (TeNTs/PtNPs) have been fully characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area diffraction patterns (SAD), X-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV). We demonstrate that the new material can be successfully employed in fuel cell either as anodic (for methanol oxidation reaction) and cathodic (for oxygen reduction reaction) electrode with high efficiency in terms of related mass activities and on-set improvement. Remarkably, the cell operates in aqueous electrolyte buffered at pH 7.0, thus avoiding acidic or alkaline conditions that may lead e. g. to Pt dissolution (at low pH) and paving the way for the development of biocompatible devices and on chip fuel cells.

Since the spread of the deadly virus SARS-CoV2 in late 2019, researchers have restlessly been seeking for unraveling how the virus factually enters the host cells. Some proteins on each side of the interaction between the virus and the host cells are involved as the major contributors to this process: 1- the nano-machine Spike protein on behalf of the virus, 2- angiotensin converting enzyme II, the mono-carboxypeptidase and the key component of renin angiotensin system on behalf of the host cell, 3- some host proteases and proteins exploited by SARS-CoV2, In this review, the complex process of SARS-CoV2 entrance into the host cells with the contribution of the involved host proteins as well as the sequential conformational changes in the Spike protein tending to increase the probability of complexification of the latter with angiotensin converting enzyme II, the receptor of the virus on the host cells, are discussed. Besides, the release of the catalytic ectodomain of angiotensin converting enzyme II as its soluble form in the extracellular space and its positive or negative impact on the infectivity of the virus are considered.

Linear regression is a basic tool in mobile robotics, since it enables accurate estimation of straight lines from range-bearing scans or in digital images, which is a prerequisite for reliable data association and sensor fusing in the context of feature-based SLAM. This paper discusses, extends and compares existing algorithms for line fitting applicable also in case of strong covariances between the coordinates at each single data point, which must not be neglected if range-bearing sensors are used. Besides, particularly the determination of the covariance matrix is considered, which is required for stochastic modeling. The main contribution is a new error model of straight lines in closed form for calculating fast and reliably the covariance matrix dependent on just a few comprehensible and easily obtainable parameters. The model can be applied widely in any case when a line is fitted from a number of distinct points also without a-priori knowledge of the specific measurement noise. By means of extensive simulations the performance and robustness of the new model in comparison to existing approaches is shown.

Poor survival of human pluripotent stem cells (hPSCs) following freezing, thawing, or passaging hinders maintenance and differentiation in stem cell research. Rho-associated kinases (ROCKs) play a crucial role in hPSC survival. To date, a typical ROCK inhibitor, Y-27632, has been the primary agent used in hPSC research. Here, we report that another ROCK inhibitor, fasudil, can be used as an alternative. Fasudil increased hPSC growth due to survival rather than proliferation following thawing and passaging, similar to Y-27632. It did not affect pluripotency and genetic integrity including mitochondrial genome (mtDNA). Notably, the genes related to metabolism, mTORC1, and TP53 have mainly displayed a faster recovery pattern with ROCK inhibitors than control. Furthermore, fasudil was confirmed as useful for the single dissociation of hPSCs and for aggregation. It also increased retinal pigment epithelium (RPE) differentiation and the survival of neural crest cells during differentiation. These findings suggest that fasudil can replace Y-27632 for use in stem cell research.

The development of 3D cerebral brain organoids which accurately resemble aspects of the human brain permits a more accurate characterization of physiological processes and neurological diseases. Cerebral organoids can be grown from stem cell lines with various genetic backgrounds allowing multiple neurodegenerative diseases to be modeled. While dysfunction in neurotransmission of patients with neurodegenerative diseases is expected, the impact of chronic neurodegeneration on the response to viral infection of the CNS is poorly understood. For instance, several mosquito-borne viruses like Dengue virus and West Nile Virus cause post-viral parkinsonism. How CNS infection might impact a host with inherent CNS dysfunction such as Parkinson’s Disease in poorly understood. This preliminary, observational study aimed to understand dysfunction in intrinsic and innate expression of a patient with a neurodegenerative disease and a non-affected individual in relation to potential viral infection in the CNS. Cerebral organoids were generated from human induced pluripotent stem cells with a normal genetic background or with idiopathic Parkinson’s Disease. After differentiation and maturation, organoid size, gene expression and immunofluorescence were evaluated to assess neurotransmission and innate immunity. While there was no significant difference in size of the organoids with a normal or Parkinson’s genetic background, gene expression studies identified multiple differences in innate immunity and neurotransmission. Immunofluorescence also identified differences in protein expression related to neurotransmission and innate immunity. Of note, organoids derived from a Parkinson’s patient exhibited endogenous up-regulation of dopamine and muscarinic acetylcholine receptors, GABA, glycine, and glutamate targets, and the majority of cytokines. This expression pattern suggests a chronic state of neuroexcitation and neuroinflammation in this population of organoids.