Novel biomarkers predict prognosis and drug-induced neuroendocrine differentiation in patients with prostate cancer

BackgroundA huge focus is being placed on the development of novel signatures in the form of new combinatorial regimens to distinguish the neuroendocrine (NE) characteristics from castration resistant prostate cancer (CRPC) timely and accurately, as well as predict the disease-free survival (DFS) and progression-free survival (PFS) of prostate cancer (PCa) patients.MethodsSingle cell data of 4 normal samples, 3 CRPC samples and 3 CRPC-NE samples were obtained from GEO database, and CellChatDB was used for potential intercellular communication, Secondly, using the “limma” package (v3.52.0), we obtained the differential expressed genes between CRPC and CRPC-NE both in single-cell RNA seq and bulk RNA seq samples, and discovered 12 differential genes characterized by CRPC-NE. Then, on the one hand, the diagnosis model of CRPC-NE is developed by random forest algorithm and artificial neural network (ANN) through Cbioportal database; On the other hand, using the data in Cbioportal and GEO database, the DFS and PFS prognostic model of PCa was established and verified through univariate Cox analysis, least absolute shrinkage and selection operator (Lasso) regression and multivariate Cox regression in R software. Finally, somatic mutation and immune infiltration were also discussed.ResultsOur research shows that there exists specific intercellular communication in classified clusters. Secondly, a CRPC-NE diagnostic model of six genes (HMGN2, MLLT11, SOX4, PCSK1N, RGS16 and PTMA) has been established and verified, the area under the ROC curve (AUC) is as high as 0.952 (95% CI: 0.882−0.994). The mutation landscape shows that these six genes are rarely mutated in the CRPC and NEPC samples. In addition, NE-DFS signature (STMN1 and PCSK1N) and NE-PFS signature (STMN1, UBE2S and HMGN2) are good predictors of DFS and PFS in PCa patients and better than other clinical features. Lastly, the infiltration levels of plasma cells, T cells CD4 naive, Eosinophils and Monocytes were significantly different between the CRPC and NEPC groups.ConclusionsThis study revealed the heterogeneity between CRPC and CRPC-NE from different perspectives, and developed a reliable diagnostic model of CRPC-NE and robust prognostic models for PCa

Développement et modélisation de nouveaux matériaux pour piles à combustibles à électrolyte solide

The Solid Oxide Fuel Cell (SOFC) defined by its ceramic and oxide electrolyte, is an electrochemical energy conversion device that produces electricity directly from the chemical reaction of fuel. Nowadays, apatite type rare earths silicates and germaniums attract many interests as the solid electrolyte due to the superior transport properties with high ionic conductivity and low activation energy. They can operate stably at intermediate temperature over a wide oxygen partial pressure range and maintain excellent performances, being considered as a candidate for IT-SOFC electrolytes. Among this series of conductors, the La-Si-O type has a higher conductivity and the performance would be modified by different doping elements.The objective of this thesis is to study the effects of element substitution/doping and synthesis methods on the structural and conductivity properties of apatite type lanthanum silicates. In this study, we use a double approach: a simulation approach and an experimental approach to optimize the electrolyte materials purity and performance.Using simulation approach, a first principle calculation based on DFT (Density Functional Theory) was carried out to investigate the effect on doping positions: Sr dopant at La position and Ge dopant at Si position. The calculation results give a connection to the ionic conductivity obtained by experiments.With experimental approach, we present the synthesis and characterization of Sr-doped La10Si6O27 (LSO) prepared through an optimized water-based sol-gel process. The results show that the ionic conductivity is thermally activated and values lies between 4.5×10-2 and 1×10-6 Scm-1 at 873 K as a function of the composition and powder preparation conditions.Les piles à combustibles à électrolyte solide de type SOFC permettent de transformer directement l’énergie de la réaction chimique de formation de l’eau à partir de l’hydrogène et de l’oxygène, en énergie électrique. De nos jours, les apatites de type silicates de terres rares présentent beaucoup d’intérêt comme électrolyte solide en raison de leurs propriétés de transport élevées avec une forte conductivité ionique et une faible énergie d'activation. Ils peuvent fonctionner de manière stable à une température intermédiaire sur une large plage de pression partielle d'oxygène en maintenant d'excellentes performances. Ils sont ainsi considérés comme de bons candidats pour les électrolytes de piles de type IT-SOFC. Parmi cette série de conducteurs, le type La-Si-O possède une conductivité plus élevée et leur performance serait modifiée par différents éléments dopants.L'objectif de cette thèse est d'étudier les effets des éléments de substitution / dopage ainsi que les méthodes de synthèse sur les propriétés structurales ainsi que sur la conductivité des apatites de type silicates de lanthane. Dans cette étude, nous utilisons une double approche: une approche de simulation et une approche expérimentale pour optimiser la pureté et les performances des matériaux d'électrolyte.Dans l'approche de simulation, le calcul basé sur la DFT (Théorie de la fonctionnelle de la densité) a été réalisée en vue d’étudier l'effet des positions de dopage: dopant Sr à La position de La et dopant Ge à la position de Si. Les résultats obtenus par le calcul concernant la conductivité ionique confirment ceux obtenus par l’expérience.Avec l’approche expérimentale, nous présentons la synthèse et la caractérisation de La10Si6O27 (LSO) dopé par Sr et élaboré par des procédés sol-gel. Les résultats montrent que la conductivité ionique est activé thermiquement et que les valeurs se situent entre 4,5 × 10-2 et 1 x 10-6 S·cm-1 à 873 K et dépend des conditions d’élaboration et de la composition de la poudre

Ab initio study of La10_xSrx(Si,Ge)6O27_0.5x apatite for SOFC electrolyte

International audienceApatite structure materials have outstanding performances as electrolytes for SOFC. Among them,La10_xSrx(Si,Ge)6O27_0.5x (LSO) series have attracted more attention for a higher ionic conductivity. Twodoping positions have been investigated, Sr dopant at La position and Ge dopant at Si position. DopedLSO conductivity was studied using first principle density functional theory (DFT) calculations. Withthe increase of Sr-doped ratio, the DOS (density of states) peaks above Fermi level shift to a higher energylevel. Furthermore, the electron energy gap broadening reduces the electron migration, while ion migrationwas limited. However, few changes of DOS with Ge substitution can be observed. The activationenergies of these two dopants are simulated by the energy barriers of the migration channel. We haveobserved that the two dopant positions affect the apatite ionic conductivities with different mechanisms.Indeed, La doped position change the electron energy level and activation energy. However, the Siposition can affect the density of electrons since it is surrounded by the oxygen and away from themigration channel. The calculation results of ionic conductivity are also consistent with those obtainedby experiments

Study on seismic behaviour of K-eccentrically braced steel frame with dog-bone reduced flexural link

In order to improve the plastic deformation capacity of flexural links, a K-eccentrically braced steel frame structure with the dog-bone reduced flexural link was proposed. The effects of the key parameters, such as the weakening starting point a and the weakening depth c, as well as the link spacing of the stiffeners on the seismic performance of the K-eccentrically braced steel frame structure were investigated by numerical simulations. The load carrying capacity, stiffness and energy dissipation capacity between the weakened model and the Base model were compared. The result shows that the weakening starting point a is in the range of 2hf to 3hf, the weakening depth c is in the range of 2tf to 4tf, and the spacing between stiffener is about 0.7bf, indicating that the difference between the performance of the weakened model and the Base model is not significant. The proposed dog-bone reduced design and the link spacing of the stiffeners can lead to bending plastic deformation in a larger area of the link, so that the energy-dissipating capacity of link is improved, which has some reference value for further study of flexural eccentrically braced steel frame in seismic performance

New Structural Carbons via Industrial Gas Explosion for Hybrid Cathodes in Li-S Batteries

New Structural Carbons via Industrial Gas Explosion for Hybrid Cathodes in Li-S Batterie

Synthesis of apatite type La10−xSrxSi6O27−0.5x powders for IT-SOFC using sol–gel process

International audienceApatite-type lanthanum silicates draw researchers' attention due to their good performance as electrolyte materials for IT-SOFC (intermediate temperature solid oxide fuel cells). In this paper we present the synthesis of Sr-doped La10Si6O27 obtained by optimizing a water-based sol–gel process. The relevant synthesis parameters have been investigated to get pure, highly crystalline powders. The mechanisms occurring in the sol–gel reactions are discussed to improve the process of the sol formation. Using this optimized sol–gel process, pure apatite powders have been obtained by calcination from a temperature as low as 800 °C for 2 h and characterized using scanning electron microscopy and X-ray diffraction. The sintering treatment was performed at the temperature of 1500 °C leading to well-crystallized electrolytes likely to be used in fuel cell applications. Ionic conductivities have been measured in order to investigate the effect of the Sr-doping. The results show that the ionic conductivity is thermally activated and its value lies between 3 × 10−2 and 1 × 10−6 S cm−1 at 873 K as function of the composition and powder preparation conditions