Elevated serum leptin may be associated with disease activity and secondary osteoporosis in Chinese patients with rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease in adults that is associated with significant joint issues and systemic inflammation. One of the signs of bone damage in RA is osteoporosis (OP). Leptin is an inflammatory protein that has been reported to be related to RA. The potential relationships among leptin, disease activity, and OP in Chinese patients with RA are not well known. METHODS: In total, 245 patients with RA and 120 healthy controls were included in this study. Detailed data on the clinical characteristics and laboratory features were collected. Information about physical activity and functional status was recorded using specific questionnaires. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). The MECALL castor-50-hf model X-ray scanner was used for the two-hand (including wrist) photographs. RESULTS: Serum leptin levels differed significantly between the RA group and healthy control subjects (1.27/3.29 vs. 0.17/0.24, Z=13.29, P<0.001). The positive rate of leptin protein in RA patients was 86.35%, which was higher than that in controls (19.55%) (χ2=28.51, P<0.001). Pearson's correlation test showed that morning stiffness, disease duration, joint swelling, joint tenderness, swollen joint count (SJC), tender joint count (TJC), health assessment questionnaire (HAQ) score, and Sharp-van der Heijde method (Sharp) score were positively correlated with the level of serum leptin (r=0.212, r=0.312, r=0.322, r=0.501, r=0.291, r=0.334, P<0.05). There was a clear increasing trend in the level of serum leptin according to the different disease activity scores and in the 28 joint activity (DAS28) groups (F=13.936, P<0.001). Elevated leptin was a risk factor for increased disease activity and OP according to logistic regression analysis. The median leptin level differed significantly between the normal bone mass group, osteopenia group, and OP group (P<0.001). An increased serum leptin level was a risk factor for RA-induced osteoporosis according to logistic regression analysis (P<0.001). CONCLUSION: These results suggest that the level of serum leptin is associated with disease activity and secondary OP among Chinese patients with RA. Key Points • Serum leptin levels in RA patients are higher than those in normal control group. • Leptin was associated with disease activity. • Leptin was associated with the occurrence of systemic osteoporosis and affects bone erosion in RA patients.

Angiopoietin-like protein 8 (betatrophin) inhibits hepatic gluconeogenesis through PI3K/Akt signaling pathway in diabetic mice.

BACKGROUND & AIMS: Angiopoietin-like protein 8 (ANGPTL8) is a 198 amino-acid long, novel secreted protein that is mainly expressed in the liver and brown adipose tissues. At present, evidence supporting the involvement of ANGPTL8 in the regulation of glucose metabolism is inconclusive, along with its function in the liver. Previous studies mainly focused on the effect of ANGPTL8 on glucose metabolism in non-diabetic mice, and few relevant studies in diabetic mice exist. Therefore, this study aimed to investigate the role of ANGPTL8 on glucose homeostasis and elucidate the underlying mechanisms in diabetic mice. METHODS: db/db diabetic and high-fat diet/streptozotocin-induced diabetic mice were injected with adenovirus expressing ANGPTL8 through the tail vein. Blood glucose levels were measured and glucose, insulin, and pyruvate tolerance tests were performed. To explore the molecular mechanism by which ANGPTL8 regulates hepatic glucose metabolism and manipulate mouse ANGPTL8 expression levels both in vivo and in vitro based on adenoviral transduction, gain- and loss-of-function strategies were adopted. RESULTS: Adenovirus-mediated overexpression of ANGPTL8 decreased fasting blood glucose levels and improved glucose tolerance and insulin sensitivity in db/db and high-fat diet/streptozotocin-induced diabetic mice. ANGPTL8 knockdown yielded the opposite effects. ANGPTL8 was upregulated in the cAMP/Dex-induced hepatocyte gluconeogenesis model. Moreover, ANGPTL8 overexpression in primary hepatocytes and diabetic mouse livers inhibited the expression of gluconeogenesis-related genes, including PEPCK and G6PC, by activating the AKT signaling pathway and, thereby, reducing glucose production. Therefore, the results demonstrated that ANGPTL8 improved glucose metabolism via inhibition of hepatic gluconeogenesis in diabetic mice. CONCLUSIONS: Current findings highlight a critical role of hepatic ANGPTL8 in glucose homeostasis, suggesting that increased ANGPTL8 expression could be an underlying factor for the inhibition of hepatic gluconeogenesis, which could be targeted for the prevention and treatment of type 2 diabetes.

Betatrophin for diagnosis and prognosis of mothers with gestational diabetes mellitus.

OBJECTIVES: Betatrophin is a widely used diagnostic marker for type 2 diabetes mellitus (DM), but its clinical utility in diagnosing gestational DM (GDM) is unclear. We evaluated the relationship between betatrophin and the risk of GDM as well as the ability of betatrophin to predict postpartum type 2 DM (PDM). METHODS: In total, 386 patients were categorized into those with and without PDM. All underwent the oral glucose tolerance test while pregnant. Betatrophin was assessed to examine the diagnostic characteristics of GDM. RESULTS: The betatrophin concentration was remarkably higher in patients with than without GDM. The patients were categorized into three groups; those with a betatrophin concentration of 300 to 600 pg/mL and >600 pg/mL had a higher risk of GDM after adjusting for body mass index, age, homeostatic model assessment-insulin resistance (HOMA-IR) concentration, and betatrophin concentration than those with a betatrophin concentration of <300 pg/mL. The HOMA-IR concentration tended to increase as the betatrophin concentration increased, and betatrophin was independently associated with GDM after adjusting for confounders. The betatrophin concentration was higher among pregnant patients with than without PDM. CONCLUSIONS: Betatrophin has high sensitivity but low specificity for diagnosing GDM and may be a promising predictor of PDM.

Epitaxial growth of ultraflat stanene with topological band inversion.

Two-dimensional (2D) topological materials, including quantum spin/anomalous Hall insulators, have attracted intense research efforts owing to their promise for applications ranging from low-power electronics and high-performance thermoelectrics to fault-tolerant quantum computation. One key challenge is to fabricate topological materials with a large energy gap for room-temperature use. Stanene-the tin counterpart of graphene-is a promising material candidate distinguished by its tunable topological states and sizeable bandgap. Recent experiments have successfully fabricated stanene, but none of them have yet observed topological states. Here we demonstrate the growth of high-quality stanene on Cu(111) by low-temperature molecular beam epitaxy. Importantly, we discovered an unusually ultraflat stanene showing an in-plane s-p band inversion together with a spin-orbit-coupling-induced topological gap (~0.3 eV) at the Γ point, which represents a foremost group-IV ultraflat graphene-like material displaying topological features in experiment. The finding of ultraflat stanene opens opportunities for exploring two-dimensional topological physics and device applications.

Hidden Order and Haldane-Like Phase in Molecular Chains Assembled from Conformation-Switchable Molecules.

Topological properties of matters have attracted tremendous interest in the past years due to the scientific and technological importance. It is of great interest to discover the analogs of topological phases in molecular architectures, if the key constituents of the phases are properly mimicked. Using scanning tunneling microscopy, we demonstrate that quasi-1D molecular chains assembled from conformation-switchable dibenzo[ g, p]chrysene molecules show hidden antiparallel order analogous to the hidden antiferromagnetic order in the Haldane phase, a known topological phase of quantum spin-1 chains. This is realized by mimicking the spin degree of freedom with the intramolecular helicene chiral switches and by emulating the interspin antiferromagnetic coupling with intermolecular homochiral coupling. The discovery of the molecular analog of topological matters may inspire the search of molecular architectures with nontrivial topological properties.

Construction of carbon-based two-dimensional crystalline nanostructure by chemical vapor deposition of benzene on Cu(111).

A new carbon-based two-dimensional crystalline nanostructure was discovered. The nanostructure was facilely constructed by chemical vapor deposition of benzene on Cu(111) in an ultrahigh vacuum chamber. A low temperature scanning tunneling microscopy and spectroscopy study of the nanostructure indicated that it has an orthorhombic superstructure and a semiconductor character with an energy gap of 0.8 eV. An X-ray photoelectron spectroscopy study showed that C-C(sp(2)) bonding is predominantly preserved, suggesting a framework consisting of π-conjugated building blocks. The periodic nanostructure was found to be a surprisingly excellent template for isolating and stabilizing magnetic atoms: Co atoms deposited on it can be well dispersed and form locally ordered atomic chains with their atomic magnetism preserved. Therefore the nanostructure may be suitable for organic spintronic applications. The most likely structural model for the nanostructure is proposed with the aid of density functional theory calculations and simulations, suggesting that the 2D nanostructure may consist of polyphenylene chains interconnected by Cu adatoms.

Dedicated hardware processor and corresponding system-on-chip design for real-time laser speckle imaging.

Laser speckle imaging (LSI) is a noninvasive and full-field optical imaging technique which produces two-dimensional blood flow maps of tissues from the raw laser speckle images captured by a CCD camera without scanning. We present a hardware-friendly algorithm for the real-time processing of laser speckle imaging. The algorithm is developed and optimized specifically for LSI processing in the field programmable gate array (FPGA). Based on this algorithm, we designed a dedicated hardware processor for real-time LSI in FPGA. The pipeline processing scheme and parallel computing architecture are introduced into the design of this LSI hardware processor. When the LSI hardware processor is implemented in the FPGA running at the maximum frequency of 130 MHz, up to 85 raw images with the resolution of 640×480 pixels can be processed per second. Meanwhile, we also present a system on chip (SOC) solution for LSI processing by integrating the CCD controller, memory controller, LSI hardware processor, and LCD display controller into a single FPGA chip. This SOC solution also can be used to produce an application specific integrated circuit for LSI processing.