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While weight loss is highly recommended for those with obesity, >60% will regain their lost weight. This weight cycling is associated with elevated risk of cardiovascular disease, relative to never having lost weight. How weight loss/regaindirectlyinfluence atherosclerotic inflammation is unknown. Thus, we studied short-term caloric restriction (stCR) in obese hypercholesterolemic mice, without confounding effects from changes in diet composition. Weight loss was found to promote atherosclerosis resolution independent of plasma cholesterol. From single-cell RNA-sequencing and subsequent mechanistic studies, this can be partly attributed to a unique subset of macrophages accumulating with stCR in epididymal adipose tissue (eWAT) and atherosclerotic plaques. These macrophages, distinguished by high expression ofFcgr4, help to clear necrotic cores in atherosclerotic plaques. Conversely, weight regain (WR) following stCR accelerated atherosclerosis progression with disappearance of Fcgr4+ macrophages from eWAT and plaques. Furthermore, WR caused reprogramming of immune progenitors, sustaining hyper-inflammatory responsiveness. In summary, we have developed a model to investigate the inflammatory effects of weight cycling on atherosclerosis and the interplay between adipose tissue, bone marrow, and plaques. The findings suggest potential approaches to promote atherosclerotic plaque resolution in obesity and weight cycling through induction of Fcgr4+ macrophages and inhibition of immune progenitor reprogramming.Graphical abstract

Although copper is an essential trace element for cell function and viability, its excess can lead to protein oxidation, DNA cleavage, and ultimate cell damage. Cells have established a variety of regulatory mechanisms to ensure copper ion homeostasis. In Saccharomyces cerevisiae, copper sensing and response to copper deficiency are regulated by the transcription factor Mac1. Our group has previously reported that in addition to copper, several chromatin proteins modulate Mac1 functionality. In this study, based on a synthetic growth deficiency phenotype, we showed that the Cu/Zn superoxide dismutase Sod1 plays an important role in Mac1 transcriptional activity, in unchallenged nutrient-rich growth conditions. Sod1 is a multipotent cytoplasmic and mitochondrial enzyme, whose main known function is to detoxify the cell from superoxide ions. It has been previously reported that Sod1 also enters the nucleus and affects the transcription of several genes, some of which are involved in copper homeostasis under Cu-depleted (Wood and Thiele, 2009) or only under specific oxidative stress conditions (Dong et al., 2013; Tsang et al., 2014). We have shown that Sod1 physically interacts with Mac1 transcription factor and is important for the transactivation as well as its DNA binding activities. On the other hand, a constitutively active mutant of Mac1 is not affected functionally by the Sod1 ablation, pointing out that Sod1 contributes to the maintenance of the copper-unchelated state of Mac1. In conclusion, we showed that Sod1-Mac1 interaction is vital for Mac1 functionality, regardless of copper medium deficiency, in unchallenged growth conditions, and we suggest that Sod1 enzymatic activity may modify the redox state of the cysteine-rich motifs in the Mac1 DNA-binding and transactivation domains.

As the global energy sector is expected to experience a gradual shift towards renewable energy sources, access to special metals in known resources is of growing concern within the EU and at a worldwide scale. This is a review on the Fe-Ni +/- Co-laterite deposits in the Balkan Peninsula, which are characterized by multistage weathering/redeposition and intense tectonic activities. The ICP-MS analyses of those laterites indicated that they are major natural sources of Ni and Co, with ore grading from 0.21 to 3.5 wt% Ni and 0.03 to 0.31 wt% Co, as well as a significant Sc content (average 55 mg/kg). The SEM-EDS analyses revealed that fine Fe-, Ni-, Co-, and Mn-(hydr)oxides are dominant host minerals and that the enrichment in these elements is probably controlled by the post-formation evolution of initial ore redeposition. The paucity of rare earth element (REE) within the typical Fe-Ni laterite ore and the preferential occurrence of Co (up to 0.31 wt%), REE content (up to 6000 mg/kg sigma REE), and REE-minerals along with Ni, Co, and Mn (asbolane and silicates) towards the lowermost part of the Lokris (C. Greece) laterite ore suggest that their deposition is controlled by epigenetic processes. The platinum-group element (PGE) content in those Fe-Ni laterites, reaching up to 88 mu g/kg Pt and 26 mu g/kg Pd (up to 186 mu g/kg Pd in one sample), which is higher than those in the majority of chromite deposits associated with ophiolites, may indicate important weathering and PGE supergene accumulation. Therefore, the mineralogical and geochemical features of Fe-Ni laterites from the Balkan Peninsula provide evidence for potential sources of certain critical metals and insights to suitable processing and metallurgical methods. In addition, the contamination of soil by heavy metals and irrigation groundwater by toxic Cr(VI), coupled with relatively high Cr(VI) concentrations in water leachates for laterite samples, altered ultramafic rocks and soils neighboring the mining areas and point to a potential human health risk and call for integrated water-soil-plant investigations in the basins surrounding laterite mines.