Atherosclerosis is a chronic inflammatory disease that can cause acute cardiovascular events. Activation of the NOD‐like receptor family, pyrin domain containing protein 3 (NLRP3) inflammasome enhances atherogenesis, which links lipid metabolism to sterile inflammation. This study examines the impact of an endogenous metabolite, namely ketone body 3‐hydroxybutyrate (3‐HB), on a mouse model of atherosclerosis. It is found that daily oral administration of 3‐HB can significantly ameliorate atherosclerosis. Mechanistically, 3‐HB is found to reduce the M1 macrophage proportion and promote cholesterol efflux by acting on macrophages through its receptor G‐protein‐coupled receptor 109a (Gpr109a). 3‐HB–Gpr109a signaling promotes extracellular calcium (Ca2+) influx. The elevation of intracellular Ca2+ level reduces the release of Ca2+ from the endothelium reticulum (ER) to mitochondria, thus inhibits ER stress triggered by ER Ca2+ store depletion. As NLRP3 inflammasome can be activated by ER stress, 3‐HB can inhibit the activation of NLRP3 inflammasome, which triggers the increase of M1 macrophage proportion and the inhibition of cholesterol efflux. It is concluded that daily nutritional supplementation of 3‐HB attenuates atherosclerosis in mice.

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β-Hydroxybutyrate (3HB) is a small molecule produced as a ketone body in mammalian animals. It has been found that 3HB provides not only energy for a body, it also participates in cell signal transduction events as a signal molecule. This study focuses on investigation of 3HB immunomodulatory mechanisms. Proteomic analysis indicates a new post-translational modification of β-hydroxy­butyrylation (Kbhb) on antibodies. Because of the low level of Kbhb antibodies and the associated difficulty in purifying them, simulated Kbhb antibody was produced using chemical modification in vitro. The chemically modified Kbhb antibody was shown to improve the stability of antibodies to protease and heat treatments. Furthermore, Kbhb of antibodies stabilizes the antibodies in plasma. As a remarkable example, COVID-19 neutralizing antibody B38 produced by 293T cells was Kbhb modified and stabilized in vivo, providing a strategy for the possibility of extending the protection effects of COVID-19 antibodies.

Adiponectin, an adipokine with insulin-sensitizing effect, is secreted from adipocytes into circulation as high, medium, and low molecular weight forms (HMW, MMW, and LMW). The HMW adiponectin oligomers possess the most potent insulin-sensitizing activity. WSF-P-1(N-methyl-1,2,3,4,5,6-hexahydro-1,1,5,5-tetramethyl-7H-2,4α-methanonaphthalen-7-amine) is derived from natural sesquiterpene longifolene by chemical modifications. We found that WSF-P-1 activates AMPK in both 3T3-L1 adipocytes and 293T cells in this study. Activation of AMPK by WSF-P-1 promotes the assembly of HMW adiponectin and increases the HMW/total ratio of adiponectin in 3T3-L1 adipocytes. We demonstrated that the Ca-dependent CaMKK signaling pathway is involved in WSF-P-1-induced AMPK activation and adiponectin multimerization. WSF-P-1 also activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes, making it a potential drug candidate for the treatment of type 2 diabetes, obesity, and other obesity-related metabolic diseases.

Peroxisome proliferator-activated receptor γ (PPARγ), the molecular target for antidiabetic thiazolidinediones (TZDs), is a master regulator of preadipocyte differentiation and lipid metabolism. The adverse side effects of TZDs, arising from their potent agonistic activity, can be minimized by PPARγ partial agonists or PPARγ non-agonists without loss of insulin sensitization. In this study, we reported that WSF-7, a synthetic chemical derived from natural monoterpene α-pinene, is a partial PPARγ agonist. We found that WSF-7 binds directly to PPARγ. Activation of PPARγ by WSF-7 promotes adipogenesis, adiponectin oligomerization and insulin-induced glucose uptake. WSF-7 also inhibits obesity-mediated PPARγ phosphorylation at serine (Ser)273 and improves insulin sensitivity of 3T3-L1 adipocytes. Our study suggested that WSF-7 activates PPARγ transcription by a mechanism different from that of rosiglitazone or luteolin. Therefore, WSF-7 might be a potential therapeutic drug to treat type 2 diabetes.

Scope Inflammatory bowel disease and colorectal carcinogenesis (CRC) are common diseases without effective prevention approach. 3‐Hydroxybutyrate (3HB) reported to have multiple functions as an oral food supplement. This study observes that 3HB prevents mouse colitis and CRC. Methods and Results The sensitivity of wild type (WT) and GPR109a‐/‐ mice to colitis is compared using dextran sulfate sodium salt (DSS)‐induced colitis model. Flow cytometry showed that 3HB cellular surface receptor GPR109a that can decrease the percentage of M1 macrophages from 50% of the DSS‐induced acute colitis mouse group to 42% DSS+3HB group mediating the inhibitory effect on inflammation. Bone marrow transplantation experiments further demonstrated that the function of 3HB depended on bone marrow cells. Subsequently, the sensitivity of WT and GPR109a‐/‐ mice to CRC is compared using an azoxymethane‐DSS‐induced CRC mouse model. It is found that the activation of GPR109a inhibited CRC, depended on reduced myeloid‐derived suppressor cells accumulation from 27% of the DSS group to 19% of the DSS+3HB group studied using flow cytometry. Conclusion It is concluded that 3HB significantly suppresses colonic inflammation and carcinogenesis, promising to benefit colon disease prevention in form of a food supplement.

The formation of the globalization pattern of regional ethnic culture brings new opportunities for the sustainable development of cultural capital. In order to solve the problem of mismatch between the high development demand of regional ethnic costumes and their traditional design methods, this study proposes an innovative design method for regional ethnic traditional costumes, taking the Yunjian, a cloud-shaped sash-like shoulder garment as an example. Firstly, we deeply explored the historical and cultural connotation of the Yunjian through fieldwork and literature research. Then we sorted out and refined its elements, colors and structural features. We classified the patterns according to the composition forms and clarified the path of pattern creation based on fractal theory. We combined the representative elements of Yunjian with the fractal algorithm and proposed the design model of Yunjian fractal pattern. Finally we verified the feasibility of the proposed design method through design practice. The results show that the Yunjian garment created by the method of this paper can better reflect the characteristics of fashion art and ethnic culture.

Background Muscle atrophy is an increasingly global health problem affecting millions, there is a lack of clinical drugs or effective therapy. Excessive loss of muscle mass is the typical characteristic of muscle atrophy, manifesting as muscle weakness accompanied by impaired metabolism of protein and nucleotide. (D)-3-hydroxybutyrate (3HB), one of the main components of the ketone body, has been reported to be effective for the obvious hemodynamic effects in atrophic cardiomyocytes and exerts beneficial metabolic reprogramming effects in healthy muscle. This study aims to exploit how the 3HB exerts therapeutic effects for treating muscle atrophy induced by hindlimb unloaded mice. Results Anabolism/catabolism balance of muscle protein was maintained with 3HB via the Akt/FoxO3a and the mTOR/4E-BP1 pathways; protein homeostasis of 3HB regulation includes pathways of ubiquitin–proteasomal, autophagic-lysosomal, responses of unfolded-proteins, heat shock and anti-oxidation. Metabolomic analysis revealed the effect of 3HB decreased purine degradation and reduced the uric acid in atrophied muscles; enhanced utilization from glutamine to glutamate also provides evidence for the promotion of 3HB during the synthesis of proteins and nucleotides. Conclusions 3HB significantly inhibits the loss of muscle weights, myofiber sizes and myofiber diameters in hindlimb unloaded mouse model; it facilitates positive balance of proteins and nucleotides with enhanced accumulation of glutamate and decreased uric acid in wasting muscles, revealing effectiveness for treating muscle atrophy. Graphical Abstract