Increased circulating FGF21 level predicts the burden of metabolic demands and risk of vascular diseases in adults with type 2 diabetes.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by chronic hyperglycemia and metabolic stress, involved in the stepwise development of cardiovascular complications. Fibroblast growth factor 21 (FGF21) is a novel hepatokine involved in regulating glucose and lipid metabolism, and has been linked to the prediction, treatment, and improvement of prognosis in multiple cardiovascular diseases (CVDs). The aim of this study is to explore the relationship between FGF21 levels and vascular diseases (VDs) including carotid atherosclerosis (CAS) and hypertension (HP) in patients with T2DM. METHODS: Baseline serum FGF21 was determined in a cross-sectional study of 701 patients with T2DM and 258 healthy control. RESULTS: The morbidity of CAS was increased in T2DM patients with HP as compared with those without (p < 0.001). The average serum FGF21 level of healthy was [123.9 (67.2-219.3)]. Baseline FGF21 was significantly higher in those who developed CAS or HP than in those who did not [305.9 (177.2-508.4) vs. 197.2 (129.7-308.3) pg/mL, p < 0.001]. In addition, an elevated serum FGF21 was observed in T2DM patients with HP and CAS than that of T2DM patients with CAS or HP [550.5 (312.6-711.3) vs. 305.9 pg/mL, p < 0.001]. Serum FGF21 levels were positively correlated with body mass index and carotid intima media thicknes (p < 0.05), the association remained significant after adjusting for age and T2DM duration. Furthermore, the multinomial logistic regression showed that serum FGF21 was independently associated with CAS and HP in patients with T2DM after adjustment for demographic and traditional VDs risk factors (p < 0.001). CONCLUSIONS: Baseline FGF21 is elevated in VDs during diabetes, changes of serum FGF21 levels were appropriately matched to metabolic stress. FGF21can be used as an independent predictor for diagnosing VDs and predicting prognosis.

Fibroblast growth factor 21 alleviates acetaminophen induced acute liver injury by activating Sirt1 mediated autophagy.

BACKGROUND AND AIMS: Acetaminophen (APAP) is the main cause of acute liver injury (ALI) in the Western. Our previous study has shown that fenofibrate activated hepatic expression of fibroblast growth factor 21 (FGF21) can protect the liver form APAP injuries by promoting autophagy. However, the underlying mechanism involved in FGF21-mediated autophagy remains unsolved. METHODS: The ALI mice model was established by intraperitoneal injection of APAP. To investigate the influence of FGF21 on autophagy and Sirt1 expression in APAP-induced ALI, FGF21 knockout (FGF21KO) mice and exogenously supplemented mouse recombinant FGF21 protein were used. In addition, primary isolated hepatocytes and the Sirt1 inhibitor EX527 were used to observe whether FGF21 activated autophagy in APAP injury is regulated by Sirt1 at the cellular level. RESULTS: FGF21, Sirt1, and autophagy levels increased in mice with acute liver injury (ALI) and in primary cultured hepatocytes. Deletion of the FGF21 gene exacerbated APAP-induced liver necrosis and oxidative stress, and decreased mitochondrial potential. It also reduced the mRNA and protein levels of autophagy-related proteins such as Sirt1, LC3-II, and p62, as well as the number of autophagosomes. Replenishment of FGF21 reversed these processes. In addition, EX527 partially counteracted the protective effect of FGF21 by worsening oxidative damage, mitochondrial damage, and reducing autophagy in primary liver cells treated with APAP. CONCLUSION: FGF21 increases autophagy by upregulating Sirt1 to alleviate APAP-induced injuries.

FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells.

The acquisition of ectopic fibroblast growth factor receptor 1 (FGFR1) expression is well documented in prostate cancer (PCa) progression, notably in conferring tumor growth advantage and facilitating metastasis. However, how FGFR1 contributes to PCa progression is not fully revealed. Here we report that ectopic FGFR1 in PCa cells promotes transferrin receptor 1 (TFR1) expression and expands the labile iron pool (LIP), and vice versa. We further demonstrate that FGFR1 stabilizes iron regulatory proteins 2 (IRP2) and therefore, upregulates TFR1 via promoting IRP2 binding to the IRE of TFR1. Deletion of FGFR1 in DU145 cells decreases the LIP, which potentiates the anticancer efficacy of iron chelator. Intriguingly, forced expression of IRP2 in FGFR1 depleted cells reinstates TFR1 expression and LIP, subsequently restoring the tumorigenicity of the cells. Together, our results here unravel a new mechanism by which FGFR1 drives PCa progression and suggest a potential novel target for PCa therapy.

An integrated high-flux cold atomic beam source for strontium.

We present the design, construction, and characterization of an integrated cold atomic beam source for strontium (Sr), which is based on a compact Zeeman slower for slowing the thermal atomic beam and an atomic deflector for selecting the cold flux. By adopting arrays of permanent magnets to produce the magnetic fields of the slower and the deflector, we effectively reduce the system size and power compared to traditional systems with magnetic coils. After the slower cooling, one can employ additional transverse cooling in the radial direction and improve the atom collimation. The atomic deflectors employ two stages of two-dimensional magnetic-optical trapping (MOT) to deflect the cold flux, whose atomic speed is lower than 50 m/s, by 20° from the thermal atomic beam. We characterize the cold atomic beam flux of the source by measuring the loading rate of a three-dimensional MOT. The loading rates reach up to 109 atoms/s. The setup is compact, highly tunable, lightweight, and requires low electrical power, which addresses the challenge of reducing the complexity of building optical atomic clocks and quantum simulation devices based on Sr.

Nomogram analysis of the influencing factors of diabetic foot in patients with diabetes mellitus.

PURPOSE: To explore the influencing factors of diabetic foot (DF) in diabetic patients and evaluate the influencing factors. METHODS: All 674 diabetic patients admitted to our hospital from January 2015 to June 2019 who met the research criteria were included as study subjects. Clinical data were collected retrospectively by filling in the case report form for clinical research, including the general demographic characteristics, disease history, laboratory examination results, and incidence of diabetes-related complications. Logistic regression analysis was used to screen the factors influencing DF: the nomogram method was applied to score the factors, and a scoring model was constructed. RESULTS: A total of 122 patients (18.1%) with newly diagnosed DF were identified. Multivariate analysis showed that long duration of diabetes (OR = 2.355), complicated diabetic nephropathy (OR = 3.073), and high HbA1c levels (OR = 1.885) were risk factors for DF development and that foot care education (OR = 0.473) was a protective factor. Cox proportional risk model analysis showed that, compared to patients with better control of HbA1C, the hazard ratio (HR) of DF in the HbA1 group, HbA2 group, and HbA3 group was 1.25, 1.58, and 4.71, respectively. Nomogram model analysis showed that the total score of each factor ranged from 44 to 176 points, and the corresponding risk rate ranged from 0.10 to 0.90 points. The higher the total score, the greater the risk of DF in diabetic patients; the area under the curve in the nomogram model was 0.742; 95% CI: 0.665~0.820 (P < 0.0001). CONCLUSION: The key to preventing DF is to enhance diabetic patients' education regarding DF care, improve patients' self-management abilities, and improve patients' blood glucose control.