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Diabetes osteoporosis is a chronic complication of diabetes mellitus (DM) and is associated with osteoclast formation and enhanced bone resorption. Specnuezhenide (SPN) is an active compound with anti-inflammatory and immunomodulatory properties. However, the roles of SPN in diabetic osteoporosis remain unknown. In this study, primary bone marrow macrophages (BMMs) were pretreated with SPN and were stimulated with receptor activator of nuclear factor kappa B ligand (RANKL; 50 ng/mL) to induce osteoclastogenesis. The number of osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining. The protein levels of cellular oncogene fos/nuclear factor of activated T cells c1 (c-Fos/NFATc1), nuclear factor kappa-B (NF-κB), and mitogen-activated protein kinases (MAPKs) were evaluated by western blot analysis. NF-κB luciferase assays were used to examine the role of SPN in NF-κB activation. The DM model group received a high-glucose, high-fat diet and was then intraperitoneally injected with streptozotocin (STZ). Micro-CT scanning, serum biochemical analysis, histological analysis were used to assess bone loss. We found that SPN suppressed RANKL-induced osteoclast formation and that SPN inhibited the expression of osteoclast-related genes and c-Fos/NFATc1. SPN inhibited RANKL-induced activation of NF-κB and MAPKs. In vivo experiments revealed that SPN suppressed diabetes-induced bone loss and the number of osteoclasts. Furthermore, SPN decreased the levels of bone turnover markers and increased the levels of runt-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), calcium (Ca) and phosphorus (P). SPN also regulated diabetes-related markers. This study suggests that SPN suppresses diabetes-induced bone loss by inhibiting RANKL-induced osteoclastogenesis, and provides an experimental basis for the treatment of diabetic osteoporosis.

Background: Organophosphate esters (OPEs) are common endocrine-disrupting chemicals, and OPE exposure may be associated with type 2 diabetes (T2D). However, greater knowledge regarding the biomolecular intermediators underlying the impact of OPEs on T2D in humans are needed to understand biological etiology. Objectives: We explored the associations between OPE exposure and glycometabolic markers among older Chinese adults 60- 69 years of age to elucidate the underlying mechanisms using a multi-omics approach. Methods: This was a longitudinal panel study comprising 76 healthy participants 60-69 years of age who lived in Jinan city of northern China. The study was conducted once every month for 5 months, from September 2018 to January 2019. We measured a total of 17 OPEs in the blood, 11 OPE metabolites in urine, and 4 glycometabolic markers (fasting plasma glucose, glycated serum protein, fasting insulin, and homeostatic model assessment for insulin resistance). The blood transcriptome and serum/urine metabolome were also evaluated. The associations between individual OPEs and glycometabolic markers were explored. An adverse outcome pathway (AOP) was established to determine the biomolecules mediating the associations. Results: Exposure to five OPEs and OPE metabolites (trimethylolpropane phosphate, triphenyl phosphate, tri-iso- butyl phosphate, dibutyl phosphate, and diphenyl phosphate) was associated with increased levels of glycometabolic markers. The mixture effect analysis further indicated the adverse effect of OPE mixtures. Multi-omics analyses revealed that the endogenous changes in the transcriptional and metabolic levels were associated with OPE exposure. The putative AOPs model suggested that triggers of molecular initiation events (e.g., insulin receptor and glucose transporter type 4) with subsequent key events, including disruptions in signal transduction pathways (e.g., phosphatidylinositol 3- kinase/protein kinase B and insulin secretion signaling) and biological functions (glucose uptake and insulin secretion), may constitute the diabetogenic effects of OPEs. Discussion: OPEs are associated with the elevated risk of T2D among older Chinese adults 60-69 years of age. Implementing OPE exposure reduction strategies may help reduce the T2D burden among these individuals, if the relationship is causal. https://doi.org/10.1289/EHP11896, Introduction Diabetes mellitus, mainly type 2 diabetes (T2D), is one of the four most prevalent noncommunicable diseases. (1,2) In 2021, 536.6 (10.5%) million adults 20-79 years of age worldwide were [...]

In this work, a molecularly imprinted photoelectrochemical (MIP-PEC) sensor based on a novel PEC composite of metal-organic frameworks (MOFs) and TiO 2 (NH 2 -MIL-125(Ti)-TiO 2 ) was established for the ultrasensitive and selective detection of oxytetracycline (OTC). This is the first attempt of applying MOFs in the construction of MIP-PEC sensor. The NH 2 -MIL-125(Ti)-TiO 2 was synthesized by a simple one-step solvothermal method and modified onto the surface of indium tin oxide (ITO) electrode as the photosensitive layer. Subsequently, molecularly imprinted polymer (MIP) was modified as recognition element by electropolymerization. The NH 2 -MIL-125(Ti)-TiO 2 showed an enhanced photocurrent response due to stronger light absorption capacity and matched energy band. Furthermore, MIP greatly improved the selectivity and sensitivity of the constructed PEC sensor. The photocurrent response of the MIP-PEC sensor was reduced after OTC recognition because the specific binding of OTC to the imprinted cavities blocked the electron transfer of the electrode. Under optimal experimental conditions, the MIP-PEC sensor exhibited a wide detection range from 0.1 nM to 10 μM with a low limit of detection (LOD) of 60 pM, as well as certain reproducibility, stability and good applicability in real samples. The proposed sensor provides ideas for the application of MOFs in the construction of PEC sensors and will offer an alternative method for the detection of other pollutants in the field of food safety., (Copyright © 2021 Elsevier B.V. All rights reserved.)