Per- and polyfluoroalkyl substances (PFAS) bioaccumulate in different organ systems, including bone. While existing research highlights the adverse impact of PFAS on bone density, a critical gap remains in understanding the specific effects on the bone marrow microenvironment, especially the bone marrow adipose tissue (BMAT). Changes in BMAT have been linked to various health consequences, such as the development of osteoporosis and the progression of metastatic tumors in bone. Studies presented herein demonstrate that exposure to a mixture of five environmentally relevant PFAS compounds promotes marrow adipogenesis in vitro and in vivo. We show that among the components of the mixture, PFHxS, an alternative to PFOS, has the highest propensity to accumulate in bone and effectively promote marrow adipogenesis. Utilizing RNAseq approaches, we identified the peroxisome proliferator-activated receptor (PPAR) signaling as a top pathway modulated by PFHxS exposure. Furthermore, we provide results suggesting the activation and involvement of PPAR-gamma (PPARγ) in PFHxS-mediated bone marrow adipogenesis, especially in combination with high-fat diet. In conclusion, our findings demonstrate the potential impact of elevated PFHxS levels, particularly in occupational settings, on bone health, and specifically bone marrow adiposity. This study contributes new insights into the health risks of PFHxS exposure, urging further research on the relationship between environmental factors, diet, and adipose tissue dynamics.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a lethal emergency. Delays in diagnosis and treatment are detrimental to the health of patients. Classical clinical manifestations of HLH include fever, cytopenia, liver dysfunction, central nervous system involvement, and coagulopathy.
METHODS: We report seven cases of secondary HLH in adults diagnosed from a total of 1200 bone marrow aspiration and trephine biopsy (BMAT) examinations in our center, with various presentations and underlying triggers including infection, malignancy, and autoimmune disease.
RESULTS: HLH can present with non-specific signs and symptoms.
CONCLUSIONS: Early recognition of HLH is crucial to enable the commencement of therapy as early as possible to prevent mortality resulting from multi-organ failure.

OBJECTIVE: Exposure of adipocytes to \'cool\' temperatures often found in the periphery of the body induces expression of Stearoyl-CoA Desaturase-1 (Scd1), an enzyme that converts saturated fatty acids to monounsaturated fatty acids. The goal of this study is to further investigate the roles of Scd in adipocytes.
METHODS: In this study, we employed Scd1 knockout cells and mouse models, along with pharmacological Scd1 inhibition to dissect the enzyme\'s function in adipocyte physiology.
RESULTS: Our study reveals that production of monounsaturated lipids by Scd1 is necessary for fusion of autophagosomes to lysosomes and that with a Scd1-deficiency, autophagosomes accumulate. In addition, Scd1-deficiency impairs lysosomal and autolysosomal acidification resulting in vacuole accumulation and eventual cell death. Blocking autophagosome formation or supplementation with monounsaturated fatty acids maintains vitality of Scd1-deficient adipocytes.
CONCLUSIONS: This study demonstrates the indispensable role of Scd1 in adipocyte survival, with its inhibition in vivo triggering autophagy-dependent cell death and its depletion in vivo leading to the loss of bone marrow adipocytes.

Bone marrow adipose tissue (BMAT) is hypothesized to serve as an expandable/contractible fat depot which functions, in part, to minimize energy requirements for sustaining optimal hematopoiesis. We investigated whether BMAT is required for immune reconstitution following injury. Male wild type (WBB6F1, WT) and BMAT-deficient WBB6F1/J-KitW/KitW-v/J (KitW/W-v) mice were lethally irradiated. Irradiation was followed by adoptive transfer of 1000 purified WT hematopoietic stem cells (HSCs). The extent of immune reconstitution in blood, bone marrow, and lymph nodes in the irradiated mice was determined using HSCs from green fluorescent protein (GFP)-expressing mice. We also evaluated skeletal response to treatment. Detection of GFP-positive B and T cells in peripheral blood at 4 and 9 weeks following adoptive transfer and in bone marrow and lymph nodes following necropsy revealed excellent immune reconstitution in both WT and BMAT-deficient mice. Adipocytes were numerous in the distal femur of WT mice but absent or rare in KitW/W-v mice. Bone parameters, including length, mass, density, bone volume, microarchitecture, and turnover balance, exhibited few differences between WT and BMAT-deficient mice. The minimal differences suggest that BMAT is not required for reconstitution of the immune system following lethal radiation and is not a major contributor to the skeletal phenotypes of kit signaling-deficient mice.

BACKGROUND: Large language models, such as ChatGPT by OpenAI, have demonstrated potential in various applications, including medical education. Previous studies have assessed ChatGPT\'s performance in university or professional settings. However, the model\'s potential in the context of standardized admission tests remains unexplored.
OBJECTIVE: This study evaluated ChatGPT\'s performance on standardized admission tests in the United Kingdom, including the BioMedical Admissions Test (BMAT), Test of Mathematics for University Admission (TMUA), Law National Aptitude Test (LNAT), and Thinking Skills Assessment (TSA), to understand its potential as an innovative tool for education and test preparation.
METHODS: Recent public resources (2019-2022) were used to compile a data set of 509 questions from the BMAT, TMUA, LNAT, and TSA covering diverse topics in aptitude, scientific knowledge and applications, mathematical thinking and reasoning, critical thinking, problem-solving, reading comprehension, and logical reasoning. This evaluation assessed ChatGPT\'s performance using the legacy GPT-3.5 model, focusing on multiple-choice questions for consistency. The model\'s performance was analyzed based on question difficulty, the proportion of correct responses when aggregating exams from all years, and a comparison of test scores between papers of the same exam using binomial distribution and paired-sample (2-tailed) t tests.
RESULTS: The proportion of correct responses was significantly lower than incorrect ones in BMAT section 2 (P<.001) and TMUA paper 1 (P<.001) and paper 2 (P<.001). No significant differences were observed in BMAT section 1 (P=.2), TSA section 1 (P=.7), or LNAT papers 1 and 2, section A (P=.3). ChatGPT performed better in BMAT section 1 than section 2 (P=.047), with a maximum candidate ranking of 73% compared to a minimum of 1%. In the TMUA, it engaged with questions but had limited accuracy and no performance difference between papers (P=.6), with candidate rankings below 10%. In the LNAT, it demonstrated moderate success, especially in paper 2\'s questions; however, student performance data were unavailable. TSA performance varied across years with generally moderate results and fluctuating candidate rankings. Similar trends were observed for easy to moderate difficulty questions (BMAT section 1, P=.3; BMAT section 2, P=.04; TMUA paper 1, P<.001; TMUA paper 2, P=.003; TSA section 1, P=.8; and LNAT papers 1 and 2, section A, P>.99) and hard to challenging ones (BMAT section 1, P=.7; BMAT section 2, P<.001; TMUA paper 1, P=.007; TMUA paper 2, P<.001; TSA section 1, P=.3; and LNAT papers 1 and 2, section A, P=.2).
CONCLUSIONS: ChatGPT shows promise as a supplementary tool for subject areas and test formats that assess aptitude, problem-solving and critical thinking, and reading comprehension. However, its limitations in areas such as scientific and mathematical knowledge and applications highlight the need for continuous development and integration with conventional learning strategies in order to fully harness its potential.

Bone marrow adipose tissue (BMAT) in the skeleton likely plays a variety of physiological and pathophysiological roles that are not yet fully understood. In elucidating the complex relationship between bone and BMAT, glucocorticoids (GCs) are positioned to play a key role, as they have been implicated in the differentiation of bone marrow mesenchymal stem cells (BMSCs) between osteogenic and adipogenic lineages. The purpose of this review is to illuminate aspects of both endogenous and exogenous GC signaling, including the influence of GC receptors, in mechanisms of bone aging including relationships to BMAT.
Harmful effects of GCs on bone mass involve several cellular pathways and events that can include BMSC differentiation bias toward adipogenesis and the influence of mature BMAT on bone remodeling through crosstalk. Interestingly, BMAT involvement remains poorly explored in GC-induced osteoporosis and warrants further investigation. This review provides an update on the current understanding of the role of glucocorticoids in the biology of osteoblasts and bone marrow adipocytes (BMAds).

Bone marrow adipose tissue (BMAT) levels are higher in distal femur metaphysis of female mice housed at thermoneutral (32°C) than in mice housed at 22°C, as are abdominal white adipose tissue (WAT) mass, and serum leptin levels. We performed two experiments to explore the role of increased leptin in temperature-enhanced accrual of BMAT. First, we supplemented 6-week-old female C57BL/6J (B6) mice with leptin for 2 weeks at 10 µg/d using a subcutaneously implanted osmotic pump. Controls consisted of ad libitum (ad lib) fed mice and mice pair fed to match food intake of leptin-supplemented mice. The mice were maintained at 32°C for the duration of treatment. At necropsy, serum leptin in leptin-supplemented mice did not differ from ad lib mice, suggesting suppression of endogenous leptin production. In support, Ucp1 expression in BAT, percent body fat, and abdominal WAT mass were lower in leptin-supplemented mice. Leptin-supplemented mice also had lower BMAT and higher bone formation in distal femur metaphysis compared to the ad lib group, changes not replicated by pair-feeding. In the second experiment, BMAT response was evaluated in 6-week-old female B6 wild type (WT), leptin-deficient ob/ob and leptin-treated (0.3 μg/d) ob/ob mice housed at 32°C for the 2-week duration of the treatment. Compared to mice sacrificed at baseline (22°C), BMAT increased in ob/ob mice as well as WT mice, indicating a leptin independent response to increased temperature. However, infusion of ob/ob mice with leptin, at a dose rate having negligible effects on either energy metabolism or serum leptin levels, attenuated the increase in BMAT. In summary, increased housing temperature and increased leptin have independent but opposing effects on BMAT in mice.

Bone marrow (BM) adipose tissue (BMAT), a unique adipose depot, plays an important role in diseases such as osteoporosis and bone metastasis. Precise control of mesenchymal stem cell (MSC) differentiation is critical for BMAT formation and regeneration. Here, we show that death associated protein kinase 1 (DAPK1) negatively regulates BM adipogenesis in vitro and in vivo. Prx1creDapk1loxp/loxp mice showed more adipocytes in the femur than Dapk1loxp/loxp mice. Further mechanistic analyses revealed that DAPK1 inhibits p38 mitogen-activated protein kinase (MAPK) signaling in the nucleus by binding the p38 isoform MAPK14, decreasing p38 nuclear activity, which subsequently inhibits BM adipogenesis. The inhibitory effect of DAPK1 against MAPK14 was independent of its kinase activity. In addition, the decreased DAPK1 was observed in the BM-MSCs of ageing mice. Our results reveal a previously undescribed function for DAPK1 in the regulation of adipogenesis and may also reveal the underlying mechanism of BMAT formation in ageing.

Cancers that grow in the bone marrow are for most patients scary, painful, and incurable. These cancers are especially hard to treat due to the supportive microenvironment provided by the bone marrow niche in which they reside. New therapies designed to target tumor cells have extended the life expectancy for these patients, but better therapies are needed and new ideas for how to target these cancers are crucial. This need has led researchers to interrogate whether bone marrow adipocytes (BMAds), which increase in number and size during aging and in obesity, contribute to cancer initiation or progression within the bone marrow. Across the globe, the consensus in the field is a unified \"yes\". However, how to target these adipocytes or the factors they produce and how BMAds interact with different tumor cells are open research questions. Herein, we review this research field, with the goal of accelerating research in the network of laboratories working in this area and attracting bright scientists with new perspectives and ideas to the field in order to bring about better therapies for patients with bone cancers.

The purpose of this review is to describe the in vitro and in vivo methods that researchers use to model and investigate bone marrow adipocytes (BMAds).
The bone marrow (BM) niche is one of the most interesting and dynamic tissues of the human body. Relatively little is understood about BMAds, perhaps in part because these cells do not easily survive flow cytometry and histology processing and hence have been overlooked. Recently, researchers have developed in vitro and in vivo models to study normal function and dysfunction in the BM niche. Using these models, scientists and clinicians have noticed that BMAds, which form bone marrow adipose tissue (BMAT), are able to respond to numerous signals and stimuli, and communicate with local cells and distant tissues in the body. This review provides an overview of how BMAds are modeled and studied in vitro and in vivo.