Degradation of OLEDs devices: study methods and solutions

2014 - 2015The fast technological evolution of our world requests the necessity to make this development sustainable. In order to achieve this goal more relevance has been given to the energy consumption and environmental impact of the modern society consumerism. These considerations point out the need to increase the effort in research of unconventional materials, new concept and system architecture for devices that could help to overcome these challenges. Nanotechnologies offer the best chance for this innovation and particularly organic electronics has been encouraged thanks to new attractive properties and promising applications. Organic materials could be processed in thin film accommodating the issue of preservation of manufacturing energy usage despite from bulky and costly processes of inorganic industries. Fabrication techniques, including spin or spray coating, ink-jet or roll-to-roll printing, can be applied at low-temperature and over large area substrates. This is promising to maximize production throughput and to reduce costs. Also many other advances have been reached in the electronic applications of organic materials such as the spread of light-weight, transparent, flexible and disposable devices. Particularly, in recent years, OLEDs (Organic Light Emitting Diode) have been successful commercialized both for display applications and light source. OLED-based displays are nowadays commercialized both for high performances cell displays and TVs, becoming the major competitors of other well established technologies, like LCD or LED. In imaging application, very often Active Matrix approach is used to supply the display. In recent years the use of another Organic Electronics device, Organic TFT (OTFT), has been exploited as Active Matrix driver with encouraging results. In the last years also OLED-based light source have been introduced on the market. OLED panel technology allows overcoming some of the more critical issues of the preceding technologies such as very low energy conversion, as for incandescence source light, lack of good colors and the use toxic elements as for fluorescent tube and costly manufacturing processes and point light source as for the more recent LED technology. Despite all these amazing results, important drawbacks still remain in the field of organic electronic devices. Low charge carrier mobilities or still expensive manufacturing cost, but the more critical is extreme sensitivity to ambient conditions, temperature, light, and particularly oxygen and moisture, which could degrade their optical and electrical characteristics. This work of thesis sets in this scenario and the aim of this research is the study of degradation phenomena through methodology that leads to the identification of the different mechanisms of degradation involved, responsible of device short life time. The present work has been developed focusing the attention on the various degradation mechanisms in OLED and the possibility to use their nature to develop innovative analysis methods. For this purpose has been exploited both extrinsic and intrinsic degradation. Critical issues in this field are the complexity of the involved phenomena and the relatively recent interest of the scientific community in the intrinsic degradation topic. In the organization of the thesis work, after a brief presentation of the main features of organic electronics, an overview of the basic principles of permeation and typical encapsulation solutions are presented. In particular, specific attention has been paid on barrier requirements and solutions presented to protect the devices. These solutions, besides being the way to control extrinsic degradation, are also used to isolate other degradation components becoming a tool for studying the intrinsic degradation in organic devices. It has been also pointed out the importance to evaluate the barrier characteristic in terms of WVTR and here has been presented some solution to evaluate ultra-high barrier permeation. The study has been then centered on the design and development of a Calcium corrosion test for the evaluation of ultra-high barrier. It has been investigated all the aspect of layout and setup to achieve a higher sensitivity level. This measurement method has been employed for the design and optimization of both a glass to glass and Thin Film Encapsulation barrier permeation system. In the first case (glass to glass) the developed encapsulated system has been used in an effective way to estimate lifetime of a simple OLED structure and validate the system performances. Afterwards, the investigations have been focused on intrinsic degradation process. For this purpose the glass to glass encapsulation system has been also used to neglect external agents within the development of an innovative method based on accelerated environmental aging conditions for the study of intrinsic degradation phenomena components. Thus an innovative methodology to study this issue has been proposed and tested on a case study. In order to reach this goal resulted very important to separate extrinsic degradation component from the intrinsic one so in this thesis we worked on the following topics reaching very satisfying results: • reliable evaluation of permeation barriers using the electrical calcium corrosion test • glass to glass and thin film encapsulation permeation barrier system • devices (OLED) lifetime under accelerated aging conditions • intrinsic degradation study: methodology and application Regarding the first topic a measurement system based on Calcium corrosion test has been first studied, designed and developed taking into account every detail leading to a result alteration. Then first a glass to glass and later a thin film encapsulation system has been designed and developed in the same way. The Calcium corrosion test measurement system was then used to measure the barrier performances of the developed encapsulation systems revealing values of WVTR in line with literature results obtained through the selected techniques. Particularly had been detected a WVTR value of 4 10-6 g m-2 day-1 and approximately 10-2 g m-2 day-1 respectively for glass to glass and Thin Film Encapsulation system. Regarding OLED lifetime, using simple devices, experiments were conducted for one OLED-structure processed on glass. The structure used an ITO bottom contact as well as an aluminum top contact. The realized devices after 3000 hours have lost only a 20% in luminance from the initial value validating the performances of the developed encapsulation solution for devices realized on glass substrate in the same time of observation. This result if from one side is very encouraging for lifetime issue on the other side is the key element that allows neglecting external effect during further degradation study. The results achieved on these topics results precious to focus on the last aspect faced during this work. In fact using our encapsulation system and applying different experimental techniques, typically not employed, has been possible to put in light single intrinsic degradation mechanism involved. Particularly has been decided to focus on possible phenomena that can occur during OFF-time periods (without electrically stressing the samples). Experiments have been conducted at different storage conditions on two types of blue OLEDs representing the worst stability case. This study revealed , in condition that allow to neglect other degradation source, that physical aging occurs for both types of devices, leading to irreversible time-dependent luminance loss. The proposed method in this case study (accelerated environmental aging conditions) coupled with other more common used analysis conditions allows to study the degradation topic in a more complete way. [edited by author]Il rapido sviluppo tecnologico dell’era contemporanea richiede la necessità di rendere questo processo evolutivo sostenibile. Per raggiungere questo obiettivo una grande rilevanza è stato assegnata al consumo energetico e all'impatto ambientale del moderno consumismo della nostra società. Queste considerazioni sottolineano la necessità di aumentare gli sforzi nella ricerca di materiali non convenzionali, di nuova concezione e architetture di sistema per i dispositivi che possano aiutare a superare queste sfide. Il campo delle nanotecnologie offre le migliori possibilità per rendere attuabile questo tipo di innovazione ed in particolare l’elettronica organica si è messa in luce grazie alle sue interessanti proprietà e promettenti applicazioni. I materiali organici possono essere processati sotto in film sottili mitigando così il problema del consumo di energia di produzione, a differenza dei processi complessi e costosi usati dalle industrie di produzione di materiali inorganici. I dispositivi organici inoltre possono essere realizzati impiegando tecniche di fabbricazione innovative che comprendono il rivestimento a spruzzo, la stampa a getto d'inchiostro o la stampa roll-to-roll; tali tecniche richiedono basse temperature e offrono la possibilità di realizzare dispositivi su larga scala. Anche questo aspetto risulta promettente nell’ottica della massimizzazione del throughput di produzione e della riduzione dei costi. Molti altri vantaggi sono stati raggiunti con l’applicazione all’elettronica di materiali organici come ad esempio la diffusione di dispositivi leggeri, trasparenti, flessibili e smaltibili più facilmente rispetto a quelli classici. In particolare, negli ultimi anni, gli OLED (Organic Light Emitting Diode) hanno avuto un enorme successo commerciale sia per applicazioni nei display sia come sorgente luminosa. I display OLED sono oggi utilizzati sia in schermi ad alte prestazioni per cellulari che per televisori, diventando i principali concorrenti di altre tecnologie consolidate, come LCD o LED. In applicazione di questo tipo, molto spesso l'approccio a matrice attiva è utilizzato per alimentare il display stesso. Negli ultimi anni l'uso di un altro dispositivo elettronico basato su materiali organici, il TFT organico (OTFT), è stato sfruttato per polarizzare circuiti a matrice attiva con risultati incoraggianti. Negli ultimi anni anche sorgenti di luce OLED sono state introdotte sul mercato. Questo tipo di tecnologia infatti permette di superare alcuni dei problemi più critici delle tecnologie precedenti, come la bassa conversione di energia tipica delle lampadine ad incandescenza, la mancanza di buoni colori e l'uso di elementi tossici tipiche dei tubi a fluorescenza e processi produttivi costosi e sorgenti di luce puntiformi tipici della più recente tecnologia LED. Nonostante tutti questi risultati sorprendenti, esistono ancora alcune problematiche aperte nel campo dei dispositivi elettronici organici. La scarsa mobilità dei portatori o i costi di produzione ancora oggi piuttosto elevati ne limitano per ora la diffusione massiccia, ma l’aspetto più critico riguarda l’estrema sensibilità alle condizioni ambientali, temperatura, luce, e in particolare l'ossigeno e l'umidità, che possono modificare sensibilmente le caratteristiche ottiche ed elettriche di questi materiali. Questo lavoro di tesi si sviluppa in questo contesto con lo scopo di studiare i fenomeni di degrado mediante metodologie che portino all'identificazione dei diversi meccanismi di degrado coinvolti, responsabili del breve tempo di vita dei dispositivi. Il presente lavoro è stato sviluppato focalizzando l'attenzione sui vari meccanismi di degrado nei dispositivi OLED e sulla possibilità di utilizzare la loro natura per sviluppare metodi di analisi innovativi. A questo scopo è stato studiato sia il degrado estrinseco che quello intrinseco. Le criticità di questo studio sono la complessità dei fenomeni coinvolti e l’interesse relativamente recente che la comunità scientifica ha rivolto allo studio del degrado intrinseco. Nel lavoro di tesi, dopo una breve presentazione delle caratteristiche principali dell’ elettronica organica, è stata presentata dapprima una panoramica dei principi di base dei processi di permeazione e successivamente tipiche soluzioni di incapsulamento. In particolare, l’attenzione è stata focalizzata sui requisiti di barriera e sulle soluzioni per proteggere i dispositivi. Queste soluzioni, oltre ad essere il modo per controllare la degrado estrinseca, vengono anche utilizzati per isolare altre componenti di degrado diventando uno strumento per studiare il degrado intrinseco in dispositivi organici. È stata poi sottolineata l'importanza di poter valutare le prestazioni di materiali barriera in termini di WVTR e sono state presentate alcune soluzioni per la caratterizzazione di alte barriere alla permeazione di gas. Lo studio è stato poi centrato sulla progettazione e lo sviluppo di un Calcium Test per la valutazione di barriere alla permeazione di vapor d’acqua tenendo in conto tutti gli elementi che potessero garantire un livello maggiore di sensibilità. Questo metodo di misura è stato poi impiegato per la progettazione e ottimizzazione sia di un sistema di incapsulamento rigido su vetro e sia di un sistema di incapsulamento flessibile con la tecnica Thin Film Encapsulation. Nel primo caso (vetro su vetro) il sistema incapsulato sviluppato è stato utilizzato in in modo efficace per stimare il tempo di vita di una semplice struttura OLED e convalidare le prestazioni del sistema stesso. In seguito, le indagini si sono concentrate sul processo di degradazione intrinseca. A questo scopo il sistema di incapsulamento rigido è stato utilizzato anche per trascurare agenti esterni nell'ambito dello sviluppo di un metodo innovativo per lo studio dei vari fenomeni che concorrono al degrado intrinseco basato su condizioni ambientali di invecchiamento accelerato. Infine è stata proposta e testata su un caso studio una metodologia innovativa per studiare questo problema. Per raggiungere questo obiettivo è risultato molto importante separare la componente di degrado estrinseca da quella intrinseca così in questa tesi abbiamo lavorato sui seguenti argomenti raggiungendo risultati molto soddisfacenti: • valutazione attendibile delle barriere di permeazione tramite Calcium test elettrico • sistemi di incapsulamento rigido e flessibile • tempo di vita di dispositivi OLED in condizioni di invecchiamento accelerato • studio del degrado intrinseco: metodologia e applicazioni Per quanto riguarda il primo argomento un sistema di misura basato sul Calcium test elettrico è stato dapprima studiato, progettato e sviluppato tenendo conto ogni dettaglio che potesse portare ad un'alterazione risultato. Successivamente sono stati progettati e sviluppati sia un sistema di incapsulamento rigido su vetro sia un sistema di incapsulamento flessibile. Il sistema di misura tramite Calcium test è stato poi utilizzato per valutare le proprietà barriera dei sistemi di incapsulamento sviluppati rivelando valori di WVTR in linea con i risultati di letteratura ottenuti con le tecniche selezionate. In particolare è stato rilevato un valore di WVTR pari a 4 10-6 g m-2 day-1 e circa 10-2 g m-2 day-1 rispettivamente per il sistema vetro-vetro e quello flessibile. Riguardo al tempo di vita di dispositivi OLED, sono stati realizzati, incapsulati e caraterizzati nel tempo dispositivi su vetro utilizzando semplici strutture. I dispositivi realizzati dopo 3000 ore hanno perso solo 20% di luminanza rispetto al valore iniziale validando le prestazioni della soluzione di incapsulamento rigido sviluppata. Questo risultato se da un lato è molto incoraggiante per il tempo di vita dei dispositivi dall'altra parte rappresenta l'elemento chiave che permette di trascurare gli effetti esterni durante gli ulteriori studi sul degrado. I risultati ottenuti su questi argomenti sono risultati indispensabili per concentrarsi sul degrado intrinseco. Infatti utilizzando il nostro sistema di incapsulamento e l'applicazione di diverse tecniche sperimentali, non convenzionali, è stato possibile mettere in luce un singolo meccanismo di degrado intrinseco. In particolare, è stato deciso di concentrarsi su eventuali fenomeni che possono verificarsi durante i periodi di OFF-time (senza sollecitare elettricamente i campioni). Gli esperimenti sono stati condotti in diverse condizioni di conservazione su due tipi di OLED blu che rappresentano il caso peggiore in termini di stabilità. Questo studio ha rivelato, in condizioni che permettono di trascurare le altre fonti di degrado, che entrambi i tipi di dispositivi soffrono di un degrado di tipo fisico. Il metodo proposto in questo caso studio (condizioni ambientali di invecchiamento accelerato) combinato con altre condizioni di analisi (anche utilizzate comunemente) consente di studiare l'argomento degrado in modo più completo. [a cura dell'autore]XIV n.s

Transdural Spread of Glioblastoma with Endonasal Growth in a Long-Term Survivor Patient: Case Report and Literature Review.

Glioblastoma (GBM) is the most aggressive primary tumor of the central nervous system (CNS) in adults. Its growth has been always described as locally invasive. This tumor rarely penetrates dura mater and invades extracranial structures. We present a case of GBM, which occurred in a 39-year-old man, with final involvement of the nasal cavity. The patient was operated four times in three years, and a personalized adjuvant chemotherapy regimen was administered in a neo-adjuvant fashion. Histopathological features of the tumor are described. To our knowledge, there are only 9 cases reported in the literature showing this growth pattern and the last case was reported in 1998

Adiabatic dynamics in a spin-1 chain with uniaxial single-spin anisotropy

We study the adiabatic quantum dynamics of an anisotropic spin-1 XY chain across a second order quantum phase transition. The system is driven out of equilibrium by performing a quench on the uniaxial single-spin anisotropy, that is supposed to vary linearly in time. We show that, for sufficiently large system sizes, the excess energy after the quench admits a non trivial scaling behavior that is not predictable by standard Kibble-Zurek arguments for isolated critical points or extended critical regions. This emerges from a competing effect of many accessible low-lying excited states, inside the whole continuous line of critical points.Comment: 17 pages, 8 figures, published versio

O Desenvolvimento Econômico da Venezuela no Governo de Hugo Chávez- 1999-2007

O estudo sobre a Venezuela é importante para compreender como funciona uma economia totalmente dependente de apenas um setor, no caso, o de petróleo, a commodity mais valorizada no mundo. O país possui abundante reserva desse recurso natural, com grande potencial de extração, exportação e enriquecimento, porém, apresenta sinais claros de subdesenvolvimento econômico. O trabalho irá mostrar, após um breve histórico do conturbado cenário político e econômico venezuelano, como o país se apresenta na gestão do presidente Hugo Chávez Frías. Dessa forma, serão mostradas as principais mudanças realizadas durante o seu governo, desde 1999 até 2007, verificando os resultados no campo sócio, político e econômico

Spleen histology in children with sickle cell disease and hereditary spherocytosis: Hints on the disease pathophysiology

open2Hereditary spherocytosis (HS) and sickle cell disease (SCD) are associated with splenomegaly and spleen dysfunction in pediatric patients. Scant data exist on possible correlations between spleen morphology and function in HS and SCD. This study aimed to assess the histological and morphometric features of HS and SCD spleens, in order to get possible correlations with disease pathophysiology. In a large series of spleens from SCD, HS and control patients the following parameters were considered: (i) macroscopic features; (ii) lymphoid follicle (LF) density; (iii) presence of peri-follicular marginal zones (MZs); (iv) presence of Gamna-Gandy bodies; (v) density of CD8-positive sinusoids; (vi) density of CD34-positive microvessels; (vii) presence/distribution of fibrosis and SMA-positive myoid cells; (viii) density of CD68-positive macrophages. SCD and HS spleens have similar macroscopic features. SCD spleens had lower LF density and fewer MZs than HS spleens and controls. SCD also showed lower CD8-positive sinusoid density, increased CD34-positive microvessel density and SMA-positive myoid cells, and higher prevalence of fibrosis and Gamna-Gandy bodies. HS had lower LF and CD8-positive sinusoid density than controls. No significant differences were noted in red pulp macrophages. By multivariate analysis, the majority of HS spleens clustered with controls, while SCD grouped separately. A multi-parametric score could predict the degree of spleen changes irrespective of the underlying disease. In conclusion, SCD spleens display greater histologic effacement than HS and SCD-related changes suggest impaired function due to vascular damage. These observations may contribute to guide the clinical management of patients.embargoed_20161128Alaggio, RitaAlaggio, Rita; Gamba, Piergiorgi

A Refined Single Cell Landscape of Haematopoiesis in the Mouse Foetal Liver

During prenatal life, the foetal liver is colonised by several waves of haematopoietic progenitors to act as the main haematopoietic organ. Single cell (sc) RNA-seq has been used to identify foetal liver cell types via their transcriptomic signature and to compare gene expression patterns as haematopoietic development proceeds. To obtain a refined single cell landscape of haematopoiesis in the foetal liver, we have generated a scRNA-seq dataset from a whole mouse E12.5 liver that includes a larger number of cells than prior datasets at this stage and was obtained without cell type preselection to include all liver cell populations. We combined mining of this dataset with that of previously published datasets at other developmental stages to follow transcriptional dynamics as well as the cell cycle state of developing haematopoietic lineages. Our findings corroborate several prior reports on the timing of liver colonisation by haematopoietic progenitors and the emergence of differentiated lineages and provide further molecular characterisation of each cell population. Extending these findings, we demonstrate the existence of a foetal intermediate haemoglobin profile in the mouse, similar to that previously identified in humans, and a previously unidentified population of primitive erythroid cells in the foetal liver

Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study

Atezolizumab; Isatuximab; Solid tumorsAtezolizumab; Isatuximab; Tumores sólidosAtezolizumab; Isatuximab; Tumors sòlidsBackground The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN). Patients and methods Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon’s two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME). Results Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME. Conclusions Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients.This work was sponsored by Sanofi (no grant number)

Inequalities in maternal health and pregnancy outcome among Nigerian women migrated to Italy

Among migrant women, unfavourable health conditions and adverse obstetric events are observed more often than in native-born parturients. This observational retrospective study evaluated selected pregnancy outcomes in a Nigerian population giving birth at the University Hospital of Verona. Compared to national controls, being Nigerian was associated with preterm birth (aOR 1.6, 95% CI 1.1-2.2) and Cesarean section (aOR 2.2, 95% CI 1.5-2.7). No differences were found in rates of instrumental delivery and the immigrant group had half the risk of genital tears (aOR 0.6, 95% CI 1.1-2.2) with a higher likelihood of undamaged genitals (aOR 1.5, 95% CI 1.3-2.1). Perinatal indicators of neonatal distress were increased among Nigerians, namely a low Apgar score (aOR 2.6, 95% CI 1.4-4.9), NICU admission (aOR 1.7, 95% CI 1.1-2.8), and stillbirth (aOR 4.0, 95% CI 1.3-12.8). In conclusion, sub-Saharan African women of Nigerian origin appeared more vulnerable and exposed to several adverse pregnancy outcomes. These disparities call for the improvement of obstetric care in this immigrant group. Parmis les femmes migrantes, des conditions de santé défavorables et des événements obstétricaux indésirables sont observés plus souvent que chez les parturientes natives. Cette étude rétrospective observationnelle a analysé certaines issues de la grossesse sélectionnées dans une population nigériane accouchant à l'Hôpital Universitaire de Vérone. Par rapport aux témoins nationaux, le fait d'être nigérian était associé à la prématurité (aOR 1.6, 95% CI 1.1-2.2) et à la césarienne (aOR 2.2, 95% CI 1.5-2.7). Aucune différence n'a été trouvée dans les taux d'accouchements instrumentaux et le groupe d'immigrants avait la moitié du risque de déchirures génitales (aOR 0.6, 95% CI 1.1-2.2) avec une probabilité plus élevée d'organes génitaux intacts (aOR 1.5, 95% CI 1.3-2.1). Les indicateurs périnatals de détresse néonatale ont été trouvés augmenté chez les nigérians, à savoir un faible score d'Apgar (aOR 2.6, 95% CI 1.4-4.9), l’admission en soins intensifs néonatals (aOR 1.7, 95% CI 1.1-2.8) et la mortinatalité (aOR 4.0, 95% CI 1.3-12.8). En conclusion, les femmes africaines subsahariennes d'origine nigériane semblaient plus vulnérables et exposées à plusieurs issues défavorables de la grossesse. Ces disparités appellent l'amélioration des soins obstétricaux dans ce groupe d'immigré

Differential Expression of Kisspeptin System and Kisspeptin Receptor Trafficking during Spermatozoa Transit in the Epididymis

The hypothalamus–pituitary–testis axis controls the production of spermatozoa, and the kisspeptin system, comprising Kiss1 and Kiss1 receptor (Kiss1R), is the main central gatekeeper. The activity of the kisspeptin system also occurs in testis and spermatozoa, but currently the need of peripheral kisspeptin to produce gametes is not fully understood. Hence, we characterized kisspeptin system in rat spermatozoa and epididymis caput and cauda and analyzed the possible presence of Kiss1 in the epididymal fluid. The presence of Kiss1 and Kiss1R in spermatozoa collected from epididymis caput and cauda was evaluated by Western blot; significant high Kiss1 levels in the caput (p < 0.001 vs. cauda) and constant levels of Kiss1R proteins were observed. Immunofluorescence analysis revealed that the localization of Kiss1R in sperm head shifts from the posterior region in the epididymis caput to perforatorium in the epididymis cauda. In spermatozoa-free epididymis, Western blot revealed higher expression of Kiss1 and Kiss1R in caput (p < 0.05 vs. cauda). Moreover, immunohistochemistry revealed that Kiss1 and Kiss1R proteins were mainly localized in the secretory epithelial cell types and in contractile myoid cells, respectively. Finally, both dot blot and Elisa revealed the presence of Kiss1 in the epididymal fluid collected from epididymis cauda and caput, indicating that rat epididymis and spermatozoa possess a complete kisspeptin system. In conclusion, we reported for the first time in rodents Kiss1R trafficking in spermatozoa during the epididymis transit and Kiss1 measure in the epididymal fluid, thus suggesting a possible role for the system in spermatozoa maturation and storage within the epididymis

The isoprenoid end product N6-Isopentenyladenosine inhibits inflammation in bronchial epithelial cells through modulating the NFκB pathway

N6-Isopentenyladenosine (iPA) is a cytokinin identified in plants but also present in a free form or as a modified nucleoside bound to selenocysteine tRNA in human cells. It is an adenosine modified by an isopentenyl chain which derives from dimethylallil pyrophosphate (DMAPP), an intermediate of the mevalonate pathway. iPA is required for efficient translational decoding of selenoproteins, and can modulate a variety of biological processes including cell cycle progression, DNA synthesis and apoptosis (1). Recently, it has been shown that iPA can exhibit immunomodulatory and anti-inflammatory properties by activating NK cells and modulating cytokine production in a way depending on the concentration used (2). In order to further investigate the anti-inflammatory properties of iPA and its possible mechanisms of action, we analyzed its ability to inhibit TNFα-induced inflammation, either in normal human bronchial epithelial cells or in a model of exacerbated inflammation represented by bronchial cells derived from a Cystic Fibrosis (CF) patient bearing the ΔF508 mutation. Results showed that iPA inhibited IL-8 and RANTES release in both type of cells in a different manner. The analysis of the key enzymes of the STAT3 and NF-κB signalling pathways showed that iPA decreased the phosphorylation of STAT3 enzyme and markedly increased the expression of the direct NF-κB inhibitor, IκBα. These results were corroborated analyzing directly the NF-κB activity in HEK 293/T cells transfected with a NF-κB reporter plasmid. In these cells, iPA was also able to decrease IκBα levels. Of interest, we found that iPA also increased the expression of the antioxidant selenoprotein glutathione peroxidase only in CF cells. Altogether these data suggest that iPA can negatively regulate inflammation with a general mechanism of action involving the inhibition of NF-κB pathway but also propose that, in the presence of an altered inflammatory response such as in CF disease, iPA might act by modulating expression and/or synthesis of glutathione peroxidase