Beige fat dissipates energy and functions as a defense against cold and obesity, but the mechanism for its development is unclear. We found that interleukin (IL)-25 signaling through its cognate receptor, IL-17 receptor B (IL-17RB), increased in adipose tissue after cold exposure and β3-adrenoceptor agonist stimulation. IL-25 induced beige fat formation in white adipose tissue (WAT) by releasing IL-4 and IL-13 and promoting alternative activation of macrophages that regulate innervation and up-regulate tyrosine hydroxylase (TH) up-regulation to produce more catecholamine including norepinephrine (NE). Blockade of IL-4Rα or depletion of macrophages with clodronate-loaded liposomes in vivo significantly impaired the beige fat formation in WAT. Mice fed with a high-fat diet (HFD) were protected from obesity and related metabolic disorders when given IL-25 through a process that involved the uncoupling protein 1 (UCP1)-mediated thermogenesis. In conclusion, the activation of IL-25 signaling in WAT may have therapeutic potential for controlling obesity and its associated metabolic disorders.

Background Myeloid-derived suppressor cells (MDSCs) have become increasingly recognized as facilitators of tumor development. However, the role of MDSCs in papillary thyroid carcinoma (PTC) progression has not been clearly explored. Objective： We aimed to evaluate the levels as well as function of circulating MDSCs in PTC. Methods The proportion of circulating PMN-MDSCs and M-MDSCs from patients with PTC or benign thyroid nodules and healthy controls was measured using flow cytometry. For immunosuppressive activity analysis, sorted circulating MDSCs were co-cultured with CD3/CD28-costimulated T lymphocytes and the proliferation of T cells was determined. PTC cell lines (TPC-1 and BC-PAP) were co-cultured with PMN-MDSCs, and the effects on cell migration, invasion, proliferation and apoptosis were evaluated. The differential expressed miRNAs and mRNAs and their function were also explored in TPC-1 cells cocultured with or without PMN-MDSCs. Results PMN-MDSCs were increased in the peripheral blood mononuclear cells (PBMC) of patients with PTC. Circulating PMN-MDSCs displayed strong T cell suppressive activity. PTC cells demonstrated enhanced invasive capabilities in vitro and in vivo when co-cultured with sorted PMN-MDSCs. PMN-MDSCs decreased expression of miR-486-3p and activated NF-κB2, a direct target of miR-486-3p. Rescue of miR-486-3p diminished the cell migration and invasion induced by PMN-MDSCs. Conclusion Collectively, our work indicates that circulating PMN-MDSCs promote PTC progression. By suppressing miR-486-3p, PMN-MDSCs promote the activity of the NF-κB2 signaling pathway, resulting in accelerated invasion of PTC cells, which may provide new therapeutic strategies for treatment of thyroid cancer.

Background: A better understanding of the current features of osteoporosis-related randomized clinical trials (RCTs) is important for improving clinical trial designs and promoting the translatability of results into benefits for patients. However, there is a lack of thorough evaluation of osteoporosis-related RCTs in middle-aged and older populations. Therefore, this study aimed to investigate the characteristics of registered RCTs on osteoporosis among middle-aged and older adults on the International Clinical Trials Registry Platform (ICTRP). Methods: Osteoporosis-related RCTs registered on the ICTRP were searched on December 31, 2020. The main features of eligible RCTs were assessed. We searched PubMed, Google scholar, Medline, and Embase databases for the publication status of completed RCTs. Results: A total of 537 osteoporosis-related RCTs were identified for analysis. The number of registered RCTs increased rapidly in 2005 (N = 47). Of these, 346 (64.4%) RCTs involved only women and 275 (51.2%) were retrospectively registered. Most RCTs were of open-label design (61.3%). The most common primary purpose of osteoporosis-related RCTs was treatment (72.3%). Intervention investigated was mainly focused on medication (62.8%), followed by lifestyle or education (19.0%), and dietary supplement (10.4%). After trial completion, the results of only 140 (35.5%) RCTs were available on the ICTRP, and the publication rate after trial completion was 30.5%. Conclusions: RCTs on osteoporosis among middle-aged and older adults were dominated by retrospectively registered and open-label trials. Most trials lacked available results and associated publications. More awareness of prospective registration and blinding design in osteoporosis-related RCTs is needed. Further, publication and dissemination of RCTs results should be promoted.

Background: Obesity has emerged as a global health challenge. Although GLP‐1 receptor agonists are showing considerable promise in weight loss, their clinical utility is partly limited by gastrointestinal adverse reactions and non‐fat weight loss side effects. UCP1‐mediated adipose thermogenesis is a critical process for body temperature maintenance and weight management. However, the lack of effective and specific adipose thermogenesis therapies has restricted its clinical application. We aimed to explore the potential of inducing adipose‐specific UCP1 overexpression via modified plasmids as an innovative therapeutic approach for obesity. Methods: We replaced the cytomegalovirus (CMV) promoter in the plasmids with two types of adipose‐specific promoters: mouse adiponectin (mADP) promoter and human adiponectin (hADP) promoter, to selectively overexpress UCP1 in adipocytes. The expression level of UCP1, weight loss, metabolic homeostasis and adipose thermogenesis effects were evaluated by immunohistochemistry, western blot, weight measurements, thermography, and comprehensive lab animal monitoring system. Results: The experiments demonstrated that the mADP promoter‐modified plasmids failed to drive UCP1 overexpression. In contrast, the hADP promoter‐modified Ucp1 overexpression (hADP‐ Ucp1 OE) plasmids achieved robust adipose‐specific UCP1 protein expression both in vitro and in vivo. In vitro experiments revealed that delivery of the hADP promoter‐modified UCP1 overexpression (hADP‐ UCP1 OE) plasmids reduced lipid droplet size and enhanced energy consumption in human adipocytes. In obese mice, administration of the hADP‐ Ucp1 OE plasmids resulted in significant weight loss and improved metabolic homeostasis. Conclusions: These findings highlight the therapeutic potential of hADP‐ UCP1 OE plasmids in obesity management. Key points: The hADP promoter‐modified plasmids selectively overexpress protein in adipose tissue. Overexpression of UCP1 driven by hADP promoter induces thermogenesis in mouse and human adipocytes in vitro. The hADP‐ Ucp1 OE treatment promotes thermogenesis and energy expenditure in mice. The hADP‐ Ucp1 OE treatment restrains the development of obesity and glucose intolerance in mice.

Objective: Medical overutilisation and underutilisation affect optimal healthcare. The Medical Maximizer-Minimizer Scale (MMS) was developed to assess individual medical maximising and minimising tendencies. Despite significant improvement in the healthcare system over the past four decades, no psychometric scales to examine treatment maximising and minimising preferences are available in China. This study aimed to translate the MMS into Chinese and examine its reliability and validity in a Chinese population.Design: This cross-sectional study was conducted in December 2019 through an online survey panel.Methods: The MMS was translated into a Chinese version (CN-MMS) using a forward–backward translation procedure. Next, a random online survey of the general population in China was conducted. Exploratory factor analysis (EFA) and confirmatory factor analysis were performed to examine the underlying factor structure of the CN-MMS. The internal consistency reliability of the scale was determined using Cronbach’s α coefficient and corrected item-total correlation. A multivariate linear regression analysis was used to examine associations between medical maximising and minimising preferences and demographic variables in the Chinese population.Results: This study included 984 participants aged 18–80 years. The CN-MMS retained 10 items, and the EFA supported a two-factor structure. The model fit for this two-factor structure of the CN-MMS was acceptable with χ²/df=3.7, comparative fit index=0.958, goodness-of-fit index=0.951, Tucker-Lewis Index=0.944 and root mean square error of approximation=0.074. The scale had a Cronbach’s α coefficient of 0.864, corrected item-total correlation of 0.451–0.667, and test–retest reliability of 0.815. Significant predictors of CN-MMS total score were nationality and household monthly income.Conclusions: The CN-MMS showed satisfactory psychometric properties. Therefore, it can be used to investigate the individual medical maximising and minimising tendencies among the general Chinese population.