TET3 plays a critical role in white adipose development and diet-induced remodeling

Maintaining healthy adipose tissue is crucial for metabolic health, requiring a deeper understanding of adipocyte development and response to high-calorie diets. This study highlights the importance of TET3 during white adipose tissue (WAT) development and expansion. Selective depletion of Tet3 in adipose precursor cells (APCs) reduces adipogenesis, protects against diet-induced adipose expansion, and enhances whole-body metabolism. Transcriptomic analysis of wild-type and Tet3 knockout (KO) APCs unveiled TET3 target genes, including Pparg and several genes linked to the extracellular matrix, pivotal for adipogenesis and remodeling. DNA methylation profiling and functional studies underscore the importance of DNA demethylation in gene regulation. Remarkably, targeted DNA demethylation at the Pparg promoter restored its transcription. In conclusion, TET3 significantly governs adipogenesis and diet-induced adipose expansion by regulating key target genes in APCs

ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease

Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics of leukocytes from patients with corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase. ROCK1/2 inhibition improved survival and histological GVHD severity in mice and was synergistic with JAK1/2 inhibition, without compromising graft-versus-leukemia-effects. ROCK1/2-inhibition in macrophages or dendritic cells prior to transfer reduced GVHD severity. Mechanistically, ROCK1/2 inhibition or ROCK1 knockdown interfered with CD80, CD86, MHC-II expression and IL-6, IL-1β, iNOS and TNF production in myeloid cells. This was accompanied by impaired T cell activation by dendritic cells and inhibition of cytoskeletal rearrangements, thereby reducing macrophage and DC migration. NF-κB signaling was reduced in myeloid cells following ROCK1/2 inhibition. In conclusion, ROCK1/2 inhibition interferes with immune activation at multiple levels and reduces acute GVHD while maintaining GVL-effects, including in corticosteroid-refractory settings

Open X-Embodiment:Robotic learning datasets and RT-X models

Large, high-capacity models trained on diverse datasets have shown remarkable successes on efficiently tackling downstream applications. In domains from NLP to Computer Vision, this has led to a consolidation of pretrained models, with general pretrained backbones serving as a starting point for many applications. Can such a consolidation happen in robotics? Conventionally, robotic learning methods train a separate model for every application, every robot, and even every environment. Can we instead train "generalist" X-robot policy that can be adapted efficiently to new robots, tasks, and environments? In this paper, we provide datasets in standardized data formats and models to make it possible to explore this possibility in the context of robotic manipulation, alongside experimental results that provide an example of effective X-robot policies. We assemble a dataset from 22 different robots collected through a collaboration between 21 institutions, demonstrating 527 skills (160266 tasks). We show that a high-capacity model trained on this data, which we call RT-X, exhibits positive transfer and improves the capabilities of multiple robots by leveraging experience from other platforms. The project website is robotics-transformer-x.github.io

Cardioprotection and lifespan extension by the natural polyamine spermidine

Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease

Cytotoxic activity of some ethnic medicinal plants from southwest of Iran

Background and objectives: Many people in ethnic groups of the world have trusted in plants for disease management and cure. Medicinal plants have always played a great role in the lives of Iranian people in the past and present and with no doubt in the future. Healers in different regions of Iran have been using medicinal herbs and one rich source for these cures is located in south-west of Iran, Kohgiluyeh va Boyer Ahmad province. Some species from this province have been selected for the present study and their cytotoxic activity has been evaluated. Methods: The methanol extracts of the 26 species were obtained by maceration and the extracts were investigated for cytotoxic activity in MTT assay. Results: The results revealed that four out of twenty six plants were toxic to MCF-7, A-549, HepG-2 and HT-29 cells. Conclusion: The findings of the present study specially the species with lower IC50 values (Eryngium billardieri and Nerium indicum) are suggested for further investigations in cancer studies

Hollow porous silicon nanospheres with 3D SiC@C coating as high-performance anodes

Silicon is regarded as one of the most promising anode candidates for next-generation Li-ion batteries because of its high theoretical capacity (4200 mAh g−1). However, the main challenge for the practical application of Si anodes is the huge volume change during (de)alloying with lithium, which leads to the pulverization of the active material and severe loss of electrical contact after cycling. Here, we develop hollow porous silicon nanospheres with three-dimensional carbon coating and SiC transition interlayer (C@SiC@Si@SiC@C) via a simple and straightforward polymer-directed strategy in order to tackle the challenges met with Si anodes. The accordingly synthesized C@SiC@Si@SiC@C anode shows high utilization of the active substance, high measured capacity (3200 mAh g−1) with almost 100% Coulombic efficiency and stable cycling performance (0.7‰ per cycle decay rate at 0.2C). Such superior performances are related to the uniquely designed structure. Firstly, the 3D carbon coating provides high electronic conductivity, and extremely small size of silicon shortens the diffusion distance for Li ions and electrons. Secondly, the stable cyclability originates from the nanoscale silicon particles reinforced by a SiC transition interlayer which effectively prevents fracture and provides robust outer layers, respectively