Human fetal brain self-organizes into long-term expanding organoids.

Human brain development involves an orchestrated, massive neural progenitor expansion while a multi-cellular tissue architecture is established. Continuously expanding organoids can be grown directly from multiple somatic tissues, yet to date, brain organoids can solely be established from pluripotent stem cells. Here, we show that healthy human fetal brain in vitro self-organizes into organoids (FeBOs), phenocopying aspects of in vivo cellular heterogeneity and complex organization. FeBOs can be expanded over long time periods. FeBO growth requires maintenance of tissue integrity, which ensures production of a tissue-like extracellular matrix (ECM) niche, ultimately endowing FeBO expansion. FeBO lines derived from different areas of the central nervous system (CNS), including dorsal and ventral forebrain, preserve their regional identity and allow to probe aspects of positional identity. Using CRISPR-Cas9, we showcase the generation of syngeneic mutant FeBO lines for the study of brain cancer. Taken together, FeBOs constitute a complementary CNS organoid platform.

Albumin Protein Impact on Early-Stage In Vitro Biodegradation of Magnesium Alloy (WE43).

Mg and its alloys are promising biodegradable materials for orthopedic implants and cardiovascular stents. The first interactions of protein molecules with Mg alloy surfaces have a substantial impact on their biocompatibility and biodegradation. We investigate the early-stage electrochemical, chemical, morphological, and electrical surface potential changes of alloy WE43 in either 154 mM NaCl or Hanks' simulated physiological solutions in the absence or presence of bovine serum albumin (BSA) protein. WE43 had the lowest electrochemical current noise (ECN) fluctuations, the highest noise resistance (Zn = 1774 Ω·cm2), and the highest total impedance (|Z| = 332 Ω·cm2) when immersed for 30 min in Hanks' solution. The highest ECN, lowest Zn (1430 Ω·cm2), and |Z| (49 Ω·cm2) were observed in the NaCl solution. In the solutions containing BSA, a unique dual-mode biodegradation was observed. Adding BSA to a NaCl solution increased |Z| from 49 to 97 Ω·cm2 and decreased the ECN signal of the alloy, i.e., the BSA inhibited corrosion. On the other hand, the presence of BSA in Hanks' solution increased the rate of biodegradation by decreasing both Zn and |Z| while increasing ECN. Finally, using scanning Kelvin probe force microscopy (SKPFM), we observed an adsorbed nanolayer of BSA with aggregated and fibrillar morphology only in Hanks' solution, where the electrical surface potential was 52 mV lower than that of the Mg oxide layer.

Organoid models of fibrolamellar carcinoma mutations reveal hepatocyte transdifferentiation through cooperative BAP1 and PRKAR2A loss.

Fibrolamellar carcinoma (FLC) is a lethal primary liver cancer, affecting young patients in absence of chronic liver disease. Molecular understanding of FLC tumorigenesis is limited, partly due to the scarcity of experimental models. Here, we CRISPR-engineer human hepatocyte organoids to recreate different FLC backgrounds, including the predominant genetic alteration, the DNAJB1-PRKACA fusion, as well as a recently reported background of FLC-like tumors, encompassing inactivating mutations of BAP1 and PRKAR2A. Phenotypic characterizations and comparisons with primary FLC tumor samples revealed mutant organoid-tumor similarities. All FLC mutations caused hepatocyte dedifferentiation, yet only combined loss of BAP1 and PRKAR2A resulted in hepatocyte transdifferentiation into liver ductal/progenitor-like cells that could exclusively grow in a ductal cell environment. BAP1-mutant hepatocytes represent primed cells attempting to proliferate in this cAMP-stimulating environment, but require concomitant PRKAR2A loss to overcome cell cycle arrest. In all analyses, DNAJB1-PRKACAfus organoids presented with milder phenotypes, suggesting differences between FLC genetic backgrounds, or for example the need for additional mutations, interactions with niche cells, or a different cell-of-origin. These engineered human organoid models facilitate the study of FLC.

Detection of Listeria monocytogenes in foods with a textile organic electrochemical transistor biosensor.

Foods contaminated by pathogens are responsible for foodborne diseases which have socioeconomic impacts. Many approaches have been extensively investigated to obtain specific and sensitive methods to detect pathogens in food, but they are often not easy to perform and require trained personnel. This work aims to propose a textile organic electrochemical transistor-based (OECT) biosensor to detect L. monocytogenes in food samples. The analyses were performed with culture-based methods, Listeria Precis™ method, PCR, and our textile OECT biosensor which used poly(3,4-ethylenedioxythiophene) (PEDOT):polystyrene sulfonate (PSS) (PEDOT:PSS) for doping the organic channel. Atomic force microscopy (AFM) was used to obtain topographic maps of the gold gate. The electrochemical activity on gate electrodes was measured and related to the concentration of DNA extracted from samples and hybridized to the specific capture probe immobilized onto the gold surface of the gate. This assay reached a limit of detection of 1.05 ng/µL, corresponding to 0.56 pM of L. monocytogenes ATCC 7644, and allowed the specific and rapid detection of L. monocytogenes in the analyzed samples. KEYPOINTS: • Textile organic electrochemical transistors functionalized with a specific DNA probe • AFM topographic and surface potential maps of a functionalized gold gate surface • Comparison between the Listeria monocytogenes Precis™ method and an OECT biosensor.

Corrosion Stiction in Automotive Braking Systems.

This review paper targets the corrosion-stiction phenomenon that can occur in automotive braking systems under static conditions in aggressive environments. The corrosion of gray cast iron discs can lead to a strong adhesion of the brake pad at the pad/disc interface that can impair the reliability and performance of the braking system. The main constituents of friction materials are initially reviewed in order to highlight the complexity of a brake pad. Corrosion-related phenomena, including stiction and stick-slip, are considered in detail to discuss the complex effect of the chemical and physical properties of friction materials on these phenomena. In addition, testing methods to evaluate the susceptibility to corrosion stiction are reviewed in this work. Electrochemical methods, including potentiodynamic polarization and electrochemical impedance spectroscopy, are useful tools for a better understanding of corrosion stiction. The development of friction materials with low susceptibility to stiction should follow a complementary approach targeting an accurate selection of the constituents, control of local conditions at the pad-disc interface, and the use of specific additives or surface treatments to reduce the corrosion susceptibility of gray cast-iron rotors.

Effect of Thermal Treatment on Corrosion Behavior of AISI 316L Stainless Steel Manufactured by Laser Powder Bed Fusion.

The effect of post-processing heat treatment on the corrosion behavior of AISI 316L stainless steel manufactured by laser powder bed fusion (L-PBF) is investigated in this work. Produced stainless steel was heat treated in a broad temperature range (from 200 °C to 1100 °C) in order to evaluate the electrochemical behavior and morphology of corrosion. The electrochemical behavior was investigated by potentiodynamic and galvanostatic polarization in a neutral and acidic (pH 1.8) 3.5% NaCl solution. The microstructure modification after heat treatment and the morphology of attack of corroded samples were evaluated by optical and scanning electron microscopy. The fine cellular/columnar microstructure typically observed for additive-manufactured stainless steel evolves into a fine equiaxed austenitic structure after thermal treatment at high temperatures (above 800 °C). The post-processing thermal treatment does not negatively affect the electrochemical behavior of additive-manufactured stainless steel even after prolonged heat treatment at 1100 °C for 8 h and 24 h. This indicates that the excellent barrier properties of the native oxide film are retained after heat treatment.

Morphological and Surface Potential Characterization of Protein Nanobiofilm Formation on Magnesium Alloy Oxide: Their Role in Biodegradation.

The formation of a protein nanobiofilm on the surface of degradable biomaterials such as magnesium (Mg) and its alloys influences metal ion release, cell adhesion/spreading, and biocompatibility. During the early stage of human body implantation, competition and interaction between inorganic species and protein molecules result in a complex film containing Mg oxide and a protein layer. This film affects the electrochemical properties of the metal surface, the protein conformational arrangement, and the electronic properties of the protein/Mg oxide interface. In this study, we discuss the impact of various simulated body fluids, including sodium chloride (NaCl), phosphate-buffered saline (PBS), and Hanks' solutions on protein adsorption, electrochemical interactions, and electrical surface potential (ESP) distribution at the adsorbed protein/Mg oxide interface. After 10 min of immersion in NaCl, atomic force microscopy (AFM) and scanning Kelvin probe force microscopy (SKPFM) showed a higher surface roughness related to enhanced degradation and lower ESP distribution on a Mg-based alloy than those in other solutions. Furthermore, adding bovine serum albumin (BSA) to all solutions caused a decline in the total surface roughness and ESP magnitude on the Mg alloy surface, particularly in the NaCl electrolyte. Using SKPFM surface analysis, we detected a protein nanobiofilm (∼10-20 nm) with an aggregated and/or fibrillary morphology only on the Mg surface exposed in Hanks' and PBS solutions; these surfaces had a lower ESP value than the oxide layer.

Effect of Heat Treatment on Microstructure and Selective Corrosion of LPBF-AlSi10Mg by Means of SKPFM and Exo-Electron Emission.

The paper deals with the evolution of the microstructure of AlSi10Mg alloy obtained by laser powder bed fusion (LPBF), as a function of the post-processing heat treatment temperature. This was approached by complementary methods including FE-scanning electron microscopy, scanning Kelvin probe force microscopy and exo-electron emission techniques. The fast cooling rate of the LPBF process as compared to traditional casting produces a very fine microstructure with high mechanical properties and corrosion resistance. However, the LPBF-AlSi10Mg alloy can be susceptible to selective corrosion at the edge of the melt pools generated by the laser scan tracks. Post-process thermal treatments of the Al alloy induce a marked modification of the silicon network at melt pool edges, in particular at high temperature such as 400 °C. It was found that this is associated to a more homogeneous distribution of Volta potential. Analysis of exo-electron emission confirms the silicon diffusion during thermal treatment. The modification of the silicon network structure of the LPBF-AlSi10Mg during thermal treatment reduces the susceptibility to selective corrosion.

The Organoid Era Permits the Development of New Applications to Study Glioblastoma.

Glioblastoma (GB) is the most frequent and aggressive type of glioma. The lack of reliable GB models, together with its considerable clinical heterogeneity, has impaired a comprehensive investigation of the mechanisms that lead to tumorigenesis, cancer progression, and response to treatments. Recently, 3D cultures have opened the possibility to overcome these challenges and cerebral organoids are emerging as a leading-edge tool in GB research. The opportunity to easily engineer brain organoids via gene editing and to perform co-cultures with patient-derived tumor spheroids has enabled the analysis of cancer development in a context that better mimics brain tissue architecture. Moreover, the establishment of biobanks from GB patient-derived organoids represents a crucial starting point to improve precision medicine therapies. This review exemplifies relevant aspects of 3D models of glioblastoma, with a specific focus on organoids and their involvement in basic and translational research.