Throughout the 20th and 21st centuries, the incidence of non-communicable diseases (NCDs), also known as chronic diseases, has been increasing worldwide. Changes in dietary and physical activity patterns, along with genetic conditions, are the main factors that modulate the metabolism of individuals, leading to the development of NCDs. Obesity, diabetes, metabolic associated fatty liver disease (MAFLD), and cardiovascular diseases (CVDs) are classified in this group of chronic diseases. Therefore, understanding the underlying molecular mechanisms of these diseases leads us to develop more accurate and effective treatments to reduce or mitigate their prevalence in the population. Given the global relevance of NCDs and ongoing research progress, this article reviews the current understanding about NCDs and their related risk factors, with a focus on obesity, diabetes, MAFLD, and CVDs, summarizing the knowledge about their pathophysiology and highlighting the currently available and emerging therapeutic strategies, especially pharmacological interventions. All of these diseases play an important role in the contamination by the SARS-CoV-2 virus, as well as in the progression and severity of the symptoms of the coronavirus disease 2019 (COVID-19). Therefore, we briefly explore the relationship between NCDs and COVID-19.

Since the removal of thiazolidinediones (TZDs) from the market, researchers have been exploring alternative anti-diabetic drugs that target PPARγ without causing adverse effects while promoting insulin sensitization by blocking serine 273 phosphorylation (Ser273 or S273). Nonetheless, the underlying mechanisms of the relationship between insulin resistance and S273 phosphorylation are still largely unknown, except for the involvement of growth differentiation factor (GDF3) regulation in the process. To further investigate potential pathways, we generated a whole organism knockin mouse line with a single S273A mutation (KI) that blocks the occurrence of its phosphorylation. Our observations of KI mice on different diets and feeding schedules revealed that they were hyperglycemic, hypoinsulinemic, presented more body fat at weaning, and presented an altered plasma and hepatic lipid profile, distinctive liver morphology and gene expression. These results suggest that total blockage of S273 phosphorylation may have unforeseen effects that, in addition to promoting insulin sensitivity, could lead to metabolic disturbances, particularly in the liver. Therefore, our findings demonstrate both the beneficial and detrimental effects of PPAR S273 phosphorylation and suggest selective modulation of this post translational modification is a viable strategy to treat type 2 diabetes.

Understanding the intracellular fate of nanoparticles is essential for designing safer and more effective nanomedicines, yet most studies rely on static observations and lack high-resolution, near-native volumetric information. Here, we establish a synchrotron-based correlative X-ray microscopy framework to investigate how fluorescent silica nanoparticles (SiNPs) redistribute within macrophages as a function of concentration and successive cell-division cycles. SiNPs were internalized by RAW 264.7 macrophages at different concentrations and analyzed using a synchrotron-based correlative X-ray microscopy workflow integrating cryogenic soft X-ray tomography (cryo-SXT), cryogenic structured illumination microscopy (cryo-SIM), and coherent X-ray ptychography, with confocal fluorescence microscopy used to establish population-level uptake tendencies. Cryo-SXT reveals a concentration-dependent redistribution of nanoparticle-containing vesicles from peripheral endosomes toward the perinuclear region, while correlative cryo-SIM confirms strict vesicular confinement, with no evidence of free nanoparticle diffusion into the nucleoplasm. At higher doses, nanoparticles approach the nuclear region via vesicles extending into nuclear-envelope invaginations, rather than by true nuclear entry. Successive cell divisions redistribute the intracellular nanoparticle load and promote stable perinuclear clustering, identifying a long-term sequestration route in macrophages. Coherent X-ray ptychography further reveals nanoscale deformations of the nuclear envelope associated with dense perinuclear vesicles. Together, these results establish synchrotron-based correlative X-ray microscopy as a mechanistic, multiscale platform for unveiling the dynamic intracellular fate of nanoparticles and providing mechanistic insight into their apparent nuclear localization.

Conventional two-dimensional (2D) histology relies upon destructive sample preparation and stereological estimation, frequently leading to sampling bias and loss of critical spatial context required for understanding renal structure relationships. Here, we detail a novel pipeline for high-resolution 3D histology of ex vivo murine kidneys using X-ray micro-computed tomography (micro-CT) at the high flux of a synchrotron light source, the architecture of the nephron and associated microvasculature necessitates three-dimensional (3D) analysis to accurately characterize its complexity. Soft-tissue contrast was optimized through an established phosphotungstic acid (PTA) staining protocol, enabling robust mapping of macro and microstructures via absorption contrast. Multi-scale imaging was performed, providing whole-organ context at resolutions around 3 μm and achieving sub-micron detail (down to 400 nm) in targeted regions of interest (ROI) of the renal cortex. Utilizing machine learning segmentation pipelines optimized for large volumetric datasets, we extracted crucial 3D quantitative morphometric data. The results presented herein demonstrate accuracy and morphological insight achievable through synchrotron-based 3D imaging, establishing a robust method for quantitative preclinical research.

The application of advanced synchrotron techniques to biological systems is frequently constrained by the limited availability of biosafety-compliant experimental environments, as most beamlines and shared research laboratories were not originally designed to operate under biological containment conditions. Consequently, many synchrotron-based studies rely on fixed, sterilized, or otherwise modified samples, restricting investigations under near-native conditions and limiting accessible experimental workflows. Here, we present a reversible Biosafety Level 2 (BSL-2) operational platform that enables advanced synchrotron-based measurements involving biological materials requiring biosafety containment without permanent infrastructure modification. The platform integrates spatial zoning, personnel qualification, controlled access, triple-containment sample transport, beamline-adapted operational procedures, and validated decontamination and restoration protocols into a unified operational framework that can be deployed and removed on demand. Implemented, validated, and institutionally approved at the SIRIUS fourth-generation synchrotron, the platform has enabled routine operation of multiple beamlines under reversible BSL-2 conditions for experiments involving human-derived and other biological samples. By preserving facility flexibility while enabling measurements under conditions closer to the native biological state, this approach expands the experimental capabilities of synchrotron facilities across spectroscopy, imaging, coherent scattering, and nanoscale characterization. The proposed methodology provides a practical and transferable pathway for integrating biosafety-compliant workflows into advanced photon science infrastructures worldwide.