Structure-function analysis of time-resolved immunological phases in metabolic dysfunction-associated fatty liver disease (MASH) comparing the NIF mouse model to human MASH.

Metabolic dysfunction-associated steatohepatitis (MASH) is a common but frequently unrecognized complication of obesity and type 2 diabetes. The association between these conditions is multifaceted and involves complex interactions between metabolic, inflammatory, and genetic factors. Here we assess the underlying structural and molecular processes focusing on the immunological phase of MASH in the nonobese inflammation and fibrosis (NIF) mouse model and compare it to the human disease as well as other murine models. Histopathology together with synchrotron-radiation-based x-ray micro-computed tomography (SRµCT) was used to investigate structural changes within the hepatic sinusoids network in the NIF mouse in comparison to patients with different severities of MASH. A time-course, bulk RNA-sequencing analysis of liver tissue from NIF mice was performed to identify the dynamics of key processes associated with the pathogenesis. Transcriptomics profiling of the NIF mouse revealed a gradual transition from an initially reactive inflammatory response to a regenerative, pro-fibrotic inflammatory response suggesting new avenues for treatment strategies that focus on immunological targets. Despite the lack of metabolic stress induced liver phenotype, a large similarity between the NIF mouse and the immunological phase of human MASH was detected. The translational value was further supported by the comparative analyses with MASH patients and additional animal models. Finally, the impact of diets known to induce metabolic stress, was explored in the NIF mouse. An obesogenic diet was found to induce key physiological, metabolic, and histologic changes akin to those observed in human MASH.

3D and Multimodal X-Ray Microscopy Reveals the Impact of Voids in CIGS Solar Cells.

Small voids in the absorber layer of thin-film solar cells are generally suspected to impair photovoltaic performance. They have been studied on Cu(In,Ga)Se2 cells with conventional laboratory techniques, albeit limited to surface characterization and often affected by sample-preparation artifacts. Here, synchrotron imaging is performed on a fully operational as-deposited solar cell containing a few tens of voids. By measuring operando current and X-ray excited optical luminescence, the local electrical and optical performance in the proximity of the voids are estimated, and via ptychographic tomography, the depth in the absorber of the voids is quantified. Besides, the complex network of material-deficit structures between the absorber and the top electrode is highlighted. Despite certain local impairments, the massive presence of voids in the absorber suggests they only have a limited detrimental impact on performance.

In situ compression of micropillars under coherent X-ray diffraction: a case study of experimental and data-analysis constraints.

Micropillar compression is a method of choice to understand mechanics at small scale. It is mainly studied with electron microscopy or white-beam micro-Laue X-ray diffraction. The aim of the present article is to show the possibilities of the use of diffraction with a coherent X-ray beam. InSb micropillars in epitaxy with their pedestals (i.e. their support) are studied in situ during compression. Firstly, an experiment using a collimated beam matching the pillar size allows determination of when the sample enters the plastic regime, independently of small defects induced by experimental artefacts. A second experiment deals with scanning X-ray diffraction maps with a nano-focused beam; despite the coherence of the beam, the contributions from the pedestal and from the micropillar in the diffraction patterns can be separated, making possible a spatially resolved study of the plastic strain fields. A quantitative measurement of the elastic strain field is nevertheless hampered by the fact that the pillar diffracts at the same angles as the pedestal. Finally, no image reconstructions were possible in these experiments, either in situ due to a blurring of the fringes during loading or post-mortem because the defect density after yielding was too high. However, it is shown how to determine the elastic bending of the pillar in the elastic regime. Bending angles of around 0.3° are found, and a method to estimate the sample's radius of curvature is suggested.

Imaging Ultrafast Dynamical Diffraction Wave Fronts in Strained Si with Coherent X Rays.

Dynamical diffraction effects in thin single crystals produce highly monochromatic parallel x-ray beams with a mutual separation of a few microns and a time delay of a few femtoseconds-the so-called echoes. This ultrafast diffraction effect is used at X-Ray Free Electron Lasers in self-seeding schemes to improve beam monochromaticity. Here, we present a coherent x-ray imaging measurement of echoes from Si crystals and demonstrate that a small surface strain can be used to tune their temporal delay. These results represent a first step toward the ambitious goal of strain tailoring new x-ray optics and, conversely, open up the possibility of using ultrafast dynamical diffraction effects to study strain in materials.

Spatio-temporal evolution of hydroxyapatite crystal thickness at the bone-implant interface.

A better understanding of bone nanostructure around the bone-implant interface is essential to improve longevity of clinical implants and decrease failure risks. This study investigates the spatio-temporal evolution of mineral crystal thickness and plate orientation in newly formed bone around the surface of a metallic implant. Standardized coin-shaped titanium implants designed with a bone chamber were inserted into rabbit tibiae for 7 and 13 weeks. Scanning measurements with micro-focused small-angle X-ray scattering (SAXS) were carried out on newly formed bone close to the implant and in control mature cortical bone. Mineral crystals were thinner close to the implant (1.8 ± 0.45 nm at 7 weeks and 2.4 ± 0.57 nm at 13 weeks) than in the control mature bone tissue (2.5 ± 0.21 nm at 7 weeks and 2.8 ± 0.35 nm at 13 weeks), with increasing thickness over healing time (+30 % in 6 weeks). These results are explained by younger bone close to the implant, which matures during osseointegration. Thinner mineral crystals parallel to the implant surface within the first 100 µm indicate that the implant affects the ultrastructure of neighbouring bone , potentially due to heterogeneous interfacial stresses, and suggest a longer maturation process of bone tissue and difficulty in binding to the metal. The bone growth kinetics within the bone chamber was derived from the spatio-temporal evolution of bone tissue's nanostructure, coupled with microtomographic imaging. The findings indicate that understanding mineral crystal thickness or plate orientation can improve our knowledge of osseointegration.

A lathe system for micrometre-sized cylindrical sample preparation at room and cryogenic temperatures.

A simple two-spindle based lathe system for the preparation of cylindrical samples intended for X-ray tomography is presented. The setup can operate at room temperature as well as under cryogenic conditions, allowing the preparation of samples down to 20 and 50 µm in diameter, respectively, within minutes. Case studies are presented involving the preparation of a brittle biomineral brachiopod shell and cryogenically fixed soft brain tissue, and their examination by means of ptychographic X-ray computed tomography reveals the preparation method to be mainly free from causing artefacts. Since this lathe system easily yields near-cylindrical samples ideal for tomography, a usage for a wide variety of otherwise challenging specimens is anticipated, in addition to potential use as a time- and cost-saving tool prior to focused ion-beam milling. Fast sample preparation becomes especially important in relation to shorter measurement times expected in next-generation synchrotron sources.

Time-domain THz spectroscopy of the characteristics of hydroxyapatite provides a signature of heating in bone tissue.

Because of the importance of bone in the biomedical, forensic and archaeological contexts, new investigation techniques are constantly required to better characterize bone ultrastructure. In the present paper, we provide an extended investigation of the vibrational features of bone tissue in the 0.1-3 THz frequency range by time-domain THz spectroscopy. Their assignment is supported by a combination of X-ray diffraction and DFT-normal modes calculations. We investigate the effect of heating on bone tissue and synthetic calcium-phosphates compounds with close structure and composition to bone mineral, including stoichiometric and non-stoichiometric hydroxyapatite (HA), tricalcium phosphate, calcium pyrophosphate and tetracalcium phosphate. We thus demonstrate that the narrow vibrational mode at 2.1 THz in bone samples exposed to thermal treatment above 750 °C arises from a lattice mode of stoichiometric HA. This feature is also observed in the other synthetic compounds, although weaker or broader, but is completely smeared out in the non-stoichiometric HA, close to natural bone mineral composition, or in synthetic poorly crystalline HA powder. The THz spectral range therefore provides a clear signature of the crystalline state of the investigated bone tissue and could, therefore be used to monitor or identify structural transitions occurring in bone upon heating.