Underlaying Mechanisms Research Articles

Thermomechanical Analyses of Alkali-Treated Coconut Husk-Bagasse Fiber-Calcium Carbonate Hybrid Composites

Natural fiber-reinforced composites can contribute to reducing carbon footprint goals due to their ability to reduce overall product weight, bio-diverse feedstocks, and recyclability potential. In this work, natural fiber-based composites containing the reinforcement of coconut husk and bagasse fiber with calcium carbonate (CaCO3) ingredients were prepared and analyzed. The composites were analyzed for mechanical, thermomechanical, and morphological properties. The reinforcements were chemically functionalized using 5% w/v NaOH to enhance their interactions with the epoxy resins. The chemical functionalization created perforation on the fiber surface, improving the interlocking of fibres with the resin material and strengthening the mechanical performance of the composite. The composites developed using modified reinforcement treatment resulted in increased tensile strength (64.8%) and flexural strength (70%). The reinforcement treatment influenced the hydrophilicity, and the water absorption of treated composites was reduced more than five times compared to the unmodified composites. Scanning electron microscopy revealed morphological changes due to fiber modification, the underlaying mechanism of fiber contraction, and enhanced fiber matrix interface interlocking and adhesion strengthening. Thermal analysis confirmed that alkali treatment improves the crystallinity of the fiber and thereto the degradation temperature of treated fiber composites (both bagasse and coconut husk), which is 375.27 °C, the highest amongst the developed hybrid composites.

Multivariate characterization of biochemical and physiological attributes of quinoa (Chenopodium quinoa Willd.) genotypes exposed to nickel stress: implications for phytoremediation.

Nickel (Ni) is an essential element for plants; however, excessive uptake of Ni causes phytotoxicity in plants. The phytotoxic effects of Ni onthe growth of quinoa and the underlaying mechanisms for Ni tolerance and phytoremediation are unknown. Hence, the present study investigated Ni tolerance and accumulation potential of two quinoa genotypes (Puno and Vikinga). Both genotypes were exposed to Ni (0, 100, 200, 300, and 400μM) in half-strength Hoagland nutrient solution for three weeks. Results revealed that shoot and root lengths, biomass, stomatal conductance, and chlorophyll contents were decreased with the increase of Ni concentration. Excessive uptake of Ni resulted in the limited uptake of K by root and its translocation to shoot. Ni caused oxidative stress in plants by overproduction of H2O2 leading to lipid peroxidation of cell membranes. Genotype Puno showed greater tolerance to Ni than Vikinga based on tolerance index, lower bioconcentration factor, and translocation factor. Greater tolerance of Puno was mainly attributed to improved physiological responses and amelioration of oxidative stress by induction of antioxidant enzymes such as peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), and ascorbate peroxidase (APX). It was revealed through multivariate analysis that Ni had strong negative correlations with growth and physiological attributes and positive associations with oxidative stress attributes. The study demonstrated genotypic variation in response to varying Ni concentrations and Puno performed better than Vikinga for phytostabilization of Ni-contaminated soils.

Doping Strategies on Improving the Hydration of Doped-BaZrO3 for Hydrogen Production in Proton-Conducting Solid Oxide Electrolysis Cells (p-SOEC)

The proton-conducting electrolyte is a key component for solid oxide electrochemical cells for delivering high-efficient hydrogen production or electricity generation. BaZrO3-based materials have been widely used due to their high proton conductivity and chemical stability. However, some issues such as low performance and electronic leakage can affect their application. In this work, we introduced a type of B-site dopant to induce higher proton concentration in BaZrO3. The proton conduction and hydration behavior as a function of dopant level are studied and compared with the conventional benchmarking electrolyte, 20 mol% yttrium doped BaZrO3 (BZY20). The underlaying mechanism for achieving a higher level of hydration is investigated by various spectroscopy techniques. The electrochemical performances are also evaluated to compare the electrolysis performance and Faradaic efficiency of p-SOEC at different operating conditions to prove the feasibility of using this new electrolyte composition.

Temperature-Dependent Evolutionary Speed Shapes the Evolution of Biodiversity Patterns Across Tetrapod Radiations.

Biodiversity varies predictably with environmental energy around the globe, but the underlaying mechanisms remain incompletely understood. The evolutionary speed hypothesis predicts that environmental kinetic energy shapes variation in speciation rates through temperature- or life history-dependent rates of evolution. To test whether variation in evolutionary speed can explain the relationship between energy and biodiversity in birds, mammals, amphibians, and reptiles, we simulated diversification over 65 myr of geological and climatic change with a spatially explicit eco-evolutionary simulation model. We modeled four distinct evolutionary scenarios in which speciation-completion rates were dependent on temperature (M1), life history (M2), temperature and life history (M3), or were independent of temperature and life-history (M0). To assess the agreement between simulated and empirical data, we performed model selection by fitting supervised machine learning models to multidimensional biodiversity patterns. We show that a model with temperature-dependent rates of speciation (M1) consistently had the strongest support. In contrast to statistical inferences, which showed no general relationships between temperature and speciation rates in tetrapods, we demonstrate how process-based modeling can disentangle the causes behind empirical biodiversity patterns. Our study highlights how environmental energy has played a fundamental role in the evolution of biodiversity over deep time. [Biogeography; diversification; machine learning; macroevolution; molecular evolution; simulation.].

Ca2+ waves and the arrhythmogenicity paradigm: role of SERCA stimulation in a CPVT mouse model

Channelopathies of the cardiac ryanodine receptor (RyR2) can predispose to life threatening catecholaminergic polymorphic ventricular tachycardias (CPVTs) during exercise or stress, however the underlaying mechanism involving complex signaling pathways is not yet fully understood. Furthermore, the resulting arrhythmogenic events on the cellular level are most likely quite diverse, depending on the mutated residue on the RyR2. Obvious possibilities are the phosphorylation of the mutated RyR2s or the stimulation of the SR Ca2+ pump (SERCA), which could increase SR Ca2+ loading.

Antisolvent Engineering to Optimize Grain Crystallinity and Hole‐Blocking Capability of Perovskite Films for High‐Performance Photovoltaics

With potential commercial applications, inverted perovskite solar cells (PSCs) have received wide-spread attentions as they are compatible with tandem devices and processed at low-temperature. Nevertheless, their efficiencies remain unsatisfactory due to insufficient film quality on hydrophobic hole transport layer and limited hole-blocking capability of the electron transport layer. Herein, 1,3,5-Tris(1-phenyl-1H-benzimidazol-2-yl)benzene (TPBi), an n-type semiconductor, is incorporated into the antisolvent to simultaneously regulate the grain growth and charge transport of perovskite films. TPBi facilitates the crystallization of perovskites along (100) orientation. Besides, TPBi is mainly distributed near the top surface of perovskite film and enhances the hole-blocking capability of the area adjacent to the surface. The superior properties of this film lead to a remarkable improvement in the open-circuit voltage of inverted PSCs. The champion device achieves a high power conversion efficiency of 21.79% while keeping ≈92% of its initial value after 1000 h storage in the ambient atmosphere. This work provides an effective way to evidently promote the performance of inverted PSCs and illustrates its underlaying mechanism.

Celecoxib repurposing in cancer therapy: molecular mechanisms and nanomedicine-based delivery technologies.

While cancer remains a significant global health problem, advances in cancer biology, deep understanding of its underlaying mechanism and identification of specific molecular targets allowed the development of new therapeutic options. Drug repurposing poses several advantages as reduced cost and better safety compared with new compounds development. COX-2 inhibitors are one of the most promising drug classes for repurposing in cancer therapy. In this review, we provide an overview of the detailed mechanism and rationale of COX-2 inhibitors as anticancer agents and we highlight the most promising research efforts on nanotechnological approaches to enhance COX-2 inhibitors delivery with special focus on celecoxib as the most widely studied agent for chemoprevention or combined with chemotherapeutic and herbal drugs for combating various cancers.

Cable Tensile Forces Associated to Winch Design in Tethered Harvesting Operations: A Case Study from the Pacific North West

Cable tensile forces in winch-assist harvesting have been investigated in order to assess the safety concerns of the technology. However, the literature is lacking, particularly in regards to the impact of winch design. In this study, a Summit Winch Assist tethering a feller-director on ground slopes up to 77% was monitored for four days. The cable tensile forces were simultaneously recorded at the harvesting and anchor machine at a frequency of 100 Hz. Cameras and GNSS devices enabled a time study of the operations and the recording of machine positions. Winch functionality and design were disclosed by the manufacturer and used for the interpretation of the results. The cable tensile forces reached 296 kN at the harvesting machine and 260 kN at the anchor machine. The slow negotiation of obstacles while moving downhill recorded the highest peaks, mainly due to threshold settings of the winch in the brake system activation. Lower but significant peaks were also recorded during stationary work tasks. The peaks, however, were limited to a few events and never exceeded the endurance limit of the cable. Overall, the study confirmed recent findings in cable tensile force analysis of active winch-assist operations and provided evidence of the underlaying mechanisms that contribute to cable tensile forces.

Relation between depression and dyslipidemia in Geriatric patients attending Family medicine Outpatients clinics, Kasralainy hospital: A cross sectional study

Background: Aging is a worldwide phenomenon. The elderly in Egypt is expected to rise to 10.9% by 2026. Prevalence of depression and cardiovascular diseases are common among the elderly population. Objective: This study was conducted to estimate the prevalence of depression among the elderly and to determine its relationship with their lipid profile. Methods: A cross-sectional descriptive study was conducted in family medicine clinics at Kasralainy hospital. One hundred and 50 elderly patients were included. Screening for depression using the short form of the Arabic version of the Geriatric Depression Scale. Levels of total cholesterol (TC), triglycerides (TG), high-density and low-density lipoprotein cholesterol (HDL and LDL) are assessed. Results: The mean age of the studied group was 73.51±8.24 years, the females represent 53.3%. More than three-fourth of the studied population had depressive symptoms with score >5. There was a statistically significant difference between normal and those with depressive symptoms regarding mean levels of cholesterol, LDL and TG with higher levels in the depression group. Also, there was a significant correlation between GDS score and levels of cholesterol, LDL and triglycerides. Conclusion: Depressive symptoms are associated with dyslipidemia characterized by high total cholesterol, high triglycerides, high LDL. Further studies assessing this relationship and its underlaying mechanism are needed. Keywords: Depressive symptoms, Dyslipidemia, Geriatrics.

Molecular Basis of Atrial Fibrillation Initiation and Maintenance

Atrial fibrillation (AF) is the most common cardiac arrhythmia, largely associated to morbidity and mortality. Over the past decades, research in appearance and progression of this arrhythmia have turned into significant advances in its management. However, the incidence of AF continues to increase with the aging of the population and many important fundamental and translational underlaying mechanisms remain elusive. Here, we review recent advances in molecular and cellular basis for AF initiation, maintenance and progression. We first provide an overview of the basic molecular and electrophysiological mechanisms that lead and characterize AF. Next, we discuss the upstream regulatory factors conducting the underlying mechanisms which drive electrical and structural AF-associated remodeling, including genetic factors (risk variants associated to AF as transcriptional regulators and genetic changes associated to AF), neurohormonal regulation (i.e., cAMP) and oxidative stress imbalance (cGMP and mitochondrial dysfunction). Finally, we discuss the potential therapeutic implications of those findings, the knowledge gaps and consider future approaches to improve clinical management.

Cardiopulmonary Exercise Testing to Assess Persistent Symptoms at 6Months in People With COVID-19 Who Survived Hospitalization: A Pilot Study.

ObjectiveThe aim of this pilot study was to assess physical fitness and its relationship with functional dyspnea in survivors of Covid-19, 6 months after their discharge from the hospital.MethodsData collected routinely from people referred for cardiopulmonary exercise testing (CPET) following hospitalization for Covid-19 were retrospectively analyzed. Persistent dyspnea was assessed using the modified Medical Research Council dyspnea (mMRC) scale.ResultsTwenty-three people with persistent symptoms were referred for CPET. Mean mMRC dyspnea score was 1 (SD = 1) and was significantly associated with VO2peak (%) (rho = −0.49). At 6 months, those hospitalized in the general ward had a slightly reduced VO2peak (87% [SD = 20]), whereas those who had been in the intensive care unit (ICU) had a moderately reduced VO2peak (77% [SD = 15]). Of note, the results of the CPET revealed that, in all patients, respiratory equivalents were high, power-to-weight ratios were low, and those who had been in the ICU had a relatively low ventilatory efficiency (mean VE/VCO2 slope = 34 [SD = 5]). Analysis of each individual showed that none had a breathing reserve <15% or 11 L/min, all had a normal exercise electrocardiogram, and 4 had a heart rate above 90%.ConclusionAt 6 months, persistent dyspnea was associated with reduced physical fitness. This study offers initial insights into the mid-term physical fitness of people who required hospitalization for Covid-19. It also provides novel pathophysiological clues about the underlaying mechanism of the physical limitations associated with persistent dyspnea. Those with persistent dyspnea should be offered a tailored rehabilitation intervention, which should probably include muscle reconditioning, breathing retraining, and perhaps respiratory muscle training.ImpactThis study is the first to show that a persistent breathing disorder (in addition to muscle deconditioning) can explain persistent symptoms 6 months after hospitalization for Covid-19 infection and suggests that a specific rehabilitation intervention is warranted.

High-temperature treatments of niobium under high vacuum, dilute air- and nitrogen-atmospheres as investigated by in situ X-ray absorption spectroscopy.

Niobium metal foils were heat-treated at 900°C under different conditions and in situ investigated with time-resolved X-ray absorption fine-structure (EXAFS and XANES) measurements. The present study aims to mimic the conditions usually applied for heat treatments of Nb materials used for superconducting radiofrequency cavities, in order to better understand the evolving processes during vacuum annealing as well as for heat treatments in controlled dilute gases. Annealing in vacuum in a commercially available cell showed a substantial amount of oxidation, so that a designated new cell was designed and realized, allowing treatments under clean high-vacuum conditions as well as under well controllable gas atmospheres. The experiments performed under vacuum demonstrated that the original structure of the Nb foils is preserved, while a detailed evaluation of the X-ray absorption fine-structure data acquired during treatments in dilute air atmospheres (10-5 mbar to 10-3 mbar) revealed a linear oxidation with the time of the treatment, and an oxidation rate proportional to the oxygen (air) pressure. The structure of the oxide appears to be very similar to that of polycrystalline NbO. The cell also permits controlled exposures to other reactive gases at elevated temperatures; here the Nb foils were exposed to dilute nitrogen atmospheres after a pre-conditioning of the studied Nb material for one hour under high-vacuum conditions, in order to imitate typical conditions used for nitrogen doping of cavity materials. Clear structural changes induced by the N2 exposure were found; however, no evidence for the formation of niobium nitride could be derived from the EXAFS and XANES experiments. The presented results establish the feasibility to study the structural changes of the Nb materials in situ during heat treatments in reactive gases with temporal resolution, which are important to better understand the underlaying mechanisms and the dynamics of phase formation during those heat treatments in more detail.

Codonopsis pilosula polysaccharide attenuates Aβ toxicity and cognitive defects in APP/PS1 mice.

Codonopsis pilosula Polysaccharides (CPPs), a traditional Chinese medicine used for thousands of years, is a potential neuroprotective polysaccharide via a relatively poorly understood mechanism. We previously reported that CPPs attenuated tau pathology in hTau transfected mice and therefore in the current work investigated the effect of CPPs on Aβ toxicity and cognitive defects in APP/PS1 mice model. It was found that one-month intragastric administration of CPPs significantly ameliorated cognitive defects in APP/PS1 mice. In addition, CPPs treatment mitigated the loss of the synaptic plasticity and increased the synaptic proteins including synaptotagmin and PSD95. The expression of Aβ42 and Aβ40 was remarkably decreased in the hippocampus of APP/PS1 mice after CPPs treatment. We also found that CPPs coincubation significantly reduced the amount of APPβ and Aβ42 expression in cells. Intriguingly, the activity of BACE1 was decreased following CPPs treatment in both the hippocampus of APP/PS1 mice and in vitro experiments. Collectively, these results indicated that CPPs attenuated Aβ pathology in APP/PS1 mice, and down-regulating BACE1 might be the underlaying mechanism which could be a therapeutic target for alleviating cognitive defects in AD pathology.

Hypothermia-Induced Ubiquitination of Voltage-Dependent Anion Channel 3 Protects BV2 Microglia Cells From Cytotoxicity Following Oxygen-Glucose Deprivation/Recovery.

Background: Hypothermia attenuates microglial activation and exerts a potential neuroprotective effect against cerebral ischemic-reperfusion (I/R) injury. However, the underlying mechanism remains to be elucidated. In this in vitro study, a model of oxygen-glucose deprivation, followed by recovery (OGD/R), was used to investigate whether hypothermia exerts anti-inflammatory and anti-apoptosis properties via enhanced ubiquitination and down-regulation of voltage-dependent anion channel 3 (VDAC3) expression.Methods: BV2 microglia were cultured under OGD for 4 h following reperfusion with or without hypothermia for 2, 4, or 8 h. M1 and M2 microglia markers [inducible nitric oxide synthase (iNOS) and arginase (Arg)1] were detected using immunofluorescence. The levels of pro-inflammatory cytokines [tumor necrosis factor (TNF) α, interleukin (IL)-1β], and anti-inflammatory factor (IL-10) were determined using enzyme-linked immunosorbent assay (ELISA). Mitochondrial membrane potential (ΔΨm) was assayed by JC-1 staining using a flow cytometer. Expression of caspase-3, cleaved caspase-3, and VDAC3 were assessed using western blot analysis. The cellular locations and interactions of ubiquitin and VDAC3 were identified using double immunofluorescence staining and immunoprecipitation (IP) assay. Also, the level of the VDAC3 mRNA was determined using a quantitative polymerase chain reaction (qPCR).Results: Hypothermia inhibited the OGD/R–induced microglia activation and differentiation into the M1 type with pro-inflammatory effect, whereas it promoted differentiation to the M2 type with anti-inflammatory effect. Hypothermia attenuated OGD/R-induced loss of Δψm, as well as the expression of apoptosis-associated proteins. Compared to normothermia, hypothermia increased the level of ubiquitinated VDAC3 in the BV2 microglia at both 2 and 8 h of reperfusion. Furthermore, hypothermia did not attenuate VDAC3 mRNA expression in OGD/R-induced microglia.Conclusions: Hypothermia treatment during reperfusion, attenuated OGD/R-induced inflammation, and apoptosis in BV2 microglia. This might be due to the promotion of VDAC3 ubiquitination, identifying VDAC3 as a new target of hypothermia.

Reproductive success in the European shag is linked to annual variation in diet and foraging trip metrics

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 619:137-147 (2019) - DOI: https://doi.org/10.3354/meps12949 Reproductive success in the European shag is linked to annual variation in diet and foraging trip metrics Svein-Håkon Lorentsen1,*, Jenny Mattisson1, Signe Christensen-Dalsgaard1,2 1Norwegian Institute for Nature Research, 7485 Trondheim, Norway 2Department of Biology, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway *Corresponding author: shl@nina.no ABSTRACT: Seabird populations have declined worldwide, and several of the potential threats are of anthropogenic origin. To understand how changes in seabird populations relate to environmental conditions it is important to know the functional relationships between prey availability and foraging behaviour, prey choice and breeding performance over several years. This was studied by linking breeding success of European shag Phalacrocorax aristotelis to variation in diet composition, and investigating the underlaying mechanism driving this variation, primarily based on behavioural costs associated with foraging, such as foraging range and diving effort. We obtained demographic data and foraging trip metrics (using GPS-loggers and time-depth recorders) from a shag colony at Sklinna, Central Norway, during the 2011-2016 breeding seasons. Breeding population size was closely and positively correlated with breeding success, which in turn was positively correlated with the proportion of saithe Pollachius virens in the diet. When the dietary proportion of uncommon prey species increased, breeding success decreased. Breeding success was negatively influenced by increasing distance travelled and accumulated dive depths on an annual basis. Summed dive depths were greatest when prey species other than saithe dominated the diet. We found that in years with low availability of saithe fewer shags bred, and those that did had lower breeding success. This indicates that in years with poor feeding conditions, there might not be sufficient resources in the foraging area to support the whole breeding population of shags. KEY WORDS: Phalacrocorax aristotelis · Seabird diet · Saithe · Pollachius virens · Foraging range · Trip length · Dive depth Full text in pdf format Supplementary material PreviousNextCite this article as: Lorentsen SH, Mattisson J, Christensen-Dalsgaard S (2019) Reproductive success in the European shag is linked to annual variation in diet and foraging trip metrics. Mar Ecol Prog Ser 619:137-147. https://doi.org/10.3354/meps12949 Export citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 619. Online publication date: June 04, 2019 Print ISSN: 0171-8630; Online ISSN: 1616-1599 Copyright © 2019 Inter-Research.

Sarcoidosis: Involvement of Genetic Factors

Sarcoidosis affects people of all racial and ethnic groups and occurs at all ages, although it usually develops before the age of 50 years, with the incidence peaking at 20 to 39 years. The incidence of Sarcoidosis varies widely throughout the world. The modern history of Sarcoidosis disease goes back to 1899 when the pioneering Norwegian dermatologist coined the term to describe skin nodules characterized by compact, sharply defined foci of epithelioid cells with large pale nuclei and also a few giant cells. Thinking this resembled sarcoma, he called the condition “multiple benign sarcoid of the skin”. This review article has focused on the underlaying mechanism which is responsible for occurance of Sarcoidosis. It also involved the genetic factors (genes) that are responsible for Sarcoidosis. Sarcoidosis has no known cause; although none of potential causes has been definitely confirmed, there is increasing evidence to support that one or more infectious agents may cause Sarcoidosis, although this organism may no longer be viable in the patient. The diagnosis of Sarcoidosis has been significantly aided by new technology. This includes the endobronchial ultrasound, which has been shown to increase the yield of needle aspiration of mediastinal and hilar lymph nodes. The positive emission tomography scan has proven useful for selecting possible biopsy sites by identifying organ involvement not appreciated by routine methodology. Emerging technologies and advances in genomics and proteomics will help to find the causes of Sarcoidosis in future, with the better understanding of pathogenesis of Sarcoidosis and to test new therapy for it

FOXO1 regulates oncogenic PKC-ι expression in melanoma inversely to c-Jun in an autocrine manner via IL-17E and ICAM-1 activation

Regardless of abundant efforts to enhance primary prevention and early detection, the number of melanoma cases in the United States has increased steadily over the past 15 years, thus greatly affecting public health and the economy. In previous studies, we demonstrated protein kinase C‑ι (PKC‑ι) to be an oncogene in melanoma, which promotes the activation of nuclear factor (NF)‑κB, thereby supporting survival and progression. In addition, we demonstrated that PKC‑ι induced the metastasis of melanoma cells by activating Vimentin, and PKC‑ι inhibition downregulated epithilial‑mesencymal transition (EMT), while inducing apoptosis. Of note, PKC‑ι specific inhibitors downregulated the expression of both PKC‑ι and phosphorylated PKC‑ι, suggesting that PKC‑ι plays a role in regulating its own expression in melanoma. In this study, we report the underlaying mechanisms of the transcriptional regulation of PKC‑ι (PRKCI gene) expression in melanoma. c‑Jun, interferon‑stimulated gene factor 3 (ISGF3), paired box gene 3 (PAX3), early growth response protein 1 (EGR1) and Forkhead box protein O1 (FOXO1), which bind on or near the promoter sequence of the PRKCI gene, were analyzed for their role in PKC‑ι regulation in SK‑MEL‑2 and MeWo cell lines. We silenced selected transcription factors using siRNA, and the results revealed that the silencing of c‑Jun and FOXO1 significantly altered the expression of PRKCI. The levels of both phosphorylated and total PKC‑ι increased upon FOXO1 silencing and decreased upon c‑Jun silencing, suggesting that c‑Jun acts as an upregulator, while FOXO1 acts as a downregulator of PRKCI expression. We also used a multiplex ELISA to analyze multiple pathways other than NF‑κB that were affected by treatment with PKC‑ι inhibitor. The silencing of NF‑κB p65 and PKC‑ι by siRNA suggested that the regulation of PKC‑ι expression was strongly associated with FOXO1. In addition, we observed a significant decrease in the mRNA levels of both interleukin (IL)‑6 and IL‑8, with a significant increase in the levels of IL‑17E and intercellular adhesion molecule 1 (ICAM‑1) upon the knockdown of expression of PKC‑ι in both cell lines. This suggested that PKC‑ι expression was affected by these cytokines in an autocrine manner. Overall, the findings of this study suggest that PKC‑ι inhibition suppresses its own expression, diminishing oncogenic signaling, while upregulating anti‑tumor signaling, thus rendering it an effective novel biomarker for use in the design of novel targeted therapeutics for melanoma.

FOXO1 regulates oncogenic PKC-ι expression in melanoma inversely to c-Jun in an autocrine manner via IL-17E and ICAM-1 activation

Regardless of abundant efforts to enhance primary prevention and early detection, the number of melanoma cases in the United States has increased steadily over the past 15 years, thus greatly affecting public health and the economy. In previous studies, we demonstrated protein kinase C‑ι (PKC‑ι) to be an oncogene in melanoma, which promotes the activation of nuclear factor (NF)‑κB, thereby supporting survival and progression. In addition, we demonstrated that PKC‑ι induced the metastasis of melanoma cells by activating Vimentin, and PKC‑ι inhibition downregulated epithilial‑mesencymal transition (EMT), while inducing apoptosis. Of note, PKC‑ι specific inhibitors downregulated the expression of both PKC‑ι and phosphorylated PKC‑ι, suggesting that PKC‑ι plays a role in regulating its own expression in melanoma. In this study, we report the underlaying mechanisms of the transcriptional regulation of PKC‑ι (PRKCI gene) expression in melanoma. c‑Jun, interferon‑stimulated gene factor 3 (ISGF3), paired box gene 3 (PAX3), early growth response protein 1 (EGR1) and Forkhead box protein O1 (FOXO1), which bind on or near the promoter sequence of the PRKCI gene, were analyzed for their role in PKC‑ι regulation in SK‑MEL‑2 and MeWo cell lines. We silenced selected transcription factors using siRNA, and the results revealed that the silencing of c‑Jun and FOXO1 significantly altered the expression of PRKCI. The levels of both phosphorylated and total PKC‑ι increased upon FOXO1 silencing and decreased upon c‑Jun silencing, suggesting that c‑Jun acts as an upregulator, while FOXO1 acts as a downregulator of PRKCI expression. We also used a multiplex ELISA to analyze multiple pathways other than NF‑κB that were affected by treatment with PKC‑ι inhibitor. The silencing of NF‑κB p65 and PKC‑ι by siRNA suggested that the regulation of PKC‑ι expression was strongly associated with FOXO1. In addition, we observed a significant decrease in the mRNA levels of both interleukin (IL)‑6 and IL‑8, with a significant increase in the levels of IL‑17E and intercellular adhesion molecule 1 (ICAM‑1) upon the knockdown of expression of PKC‑ι in both cell lines. This suggested that PKC‑ι expression was affected by these cytokines in an autocrine manner. Overall, the findings of this study suggest that PKC‑ι inhibition suppresses its own expression, diminishing oncogenic signaling, while upregulating anti‑tumor signaling, thus rendering it an effective novel biomarker for use in the design of novel targeted therapeutics for melanoma.

Effects of Jaw Periosteal Cells on Dendritic Cell Maturation.

Clinical application of tissue engineering products requires the exclusion of immune responses after implantation. We used jaw periosteal cells (JPCs) as a suitable stem cell source and analyzed herein the effects of JPCs on dendritic cell maturation after co-culturing of both cell types. Peripheral blood mononuclear cells (PBMCs) were differentiated to dendritic cells (DCs) by the addition of differentiation cocktails for 7 days in co-culture with undifferentiated and osteogenically induced JPCs. The effects of JPCs on DC maturation were analyzed at the beginning (day 7), in the middle (day 14), and at the end (day 21) of the osteogenesis process. We detected significantly lower DC numbers after co-culturing with JPCs that have previously been left untreated or osteogenically differentiated for 7, 14, and 21 days. Using gene expression analyses, significantly lower IL-12p35 and -p40 and pro-inflammatory cytokine (IFN-γ and TNF-α) levels were detected, whereas IL-8 mRNA levels were significantly higher in DCs. Furthermore, osteogenic media conditions enhanced significantly IL-10 gene expression. We concluded that undifferentiated and osteogenically differentiated JPCs had an overall inhibiting influence on dendritic cell maturation. Further studies should clarify the underlaying mechanism in depth.

Joint effect of artificial noise and primary interference on security performance of cognitive radio networks

Underlay mechanism allows concurrent communications of primary users and secondary users in cognitive radio networks (CRNs), causing mutual interference between them. However, current literature neglects primary interference or considers it as Gaussian noise. In addition, artificial noise, which is intentionally generated to interfere eavesdroppers, can improve security performance of CRNs. This paper analyzes security performance of CRNs, accounting for artificial noise and considering primary interference as non-Gaussian noise, under maximum transmit power constraint, interference power constraint, and Rayleigh fading channels. The security performance is evaluated through proposed exact expressions of secrecy outage probability, non-zero achievable secrecy rate probability, and intercept probability, which are verified by Monte-Carlo simulations. Various results demonstrate that CRNs suffer security performance saturation in the range of large maximum transmit power or large maximum interference power, and primary interference significantly deteriorates security performance while artificial noise is useful in enhancing this performance.