Diverse Bone Matrix and Mineral Alterations in Osteoporosis with Different Causes: A Solid-State NMR Study.

Osteoporosis (OP), which is a common skeletal disease with different causes, is prevalent in the aging population. Postmenopause women generally suffer from OP with bone loss due to estrogen deficiency. Diabetes is also associated with OP by complex metabolic mechanisms.

Tiaogeng decoction improves mild cognitive impairment in menopausal APP/PS1 mice through the ERs/NF-κ b/AQP1 signaling pathway.

People with mild cognitive impairment (MCI) carry a considerable risk of developing dementia. Studies have shown that female sex hormones have long-lasting neuroprotective and anti-aging properties, and the increased risk of MCI and AD is associated with the lack of estrogen during menopause. Previous studies have shown that Tiao Geng Decoction (TGD) may have antioxidant and anti apoptotic properties, which may prevent neurodegenerative diseases.

Differential contributions of G protein- or arrestin subtype-mediated signalling underlie urocortin 3-induced somatostatin secretion in pancreatic δ cells.

Background And Purpose: Pancreatic islets are modulated by cross-talk among different cell types and paracrine signalling plays important roles in maintaining glucose homeostasis. Urocortin 3 (UCN3) secreted by pancreatic β cells activates the CRF receptor (CRFR) and downstream pathways mediated by different G protein or arrestin subtypes in δ cells to cause somatostatin (SST) secretion, and constitutes an important feedback circuit for glucose homeostasis.

Experimental Approach: Here, we used Arrb1, Arrb2, Gs and Gq knockout mice, the G-shRNA-GFP lentivirus, as well as functional assays and pharmacological characterization to study how the coupling of G, G and β-arrestin1 to CRFR contributed to UCN3-induced SST secretion in pancreatic δ cells.

A distinctive subcortical functional connectivity pattern linking negative affect and treatment outcome in major depressive disorder.

Major depressive disorder (MDD) is associated with functional disturbances in subcortical regions. In this naturalistic prospective study (NCT03294525), we aimed to investigate relationships among subcortical functional connectivity (FC), mood symptom profiles and treatment outcome in MDD using multivariate methods. Medication-free participants with MDD (n = 135) underwent a functional magnetic resonance imaging scan at baseline and completed posttreatment clinical assessment after 8 weeks of antidepressant monotherapy.

High-Thermal Stable Epoxy Resin through Blending Nanoarchitectonics with Double-Decker-Shaped Polyhedral Silsesquioxane-Functionalized Benzoxazine Derivatives.

A series of di-functional benzoxazine (BZ) monomers was synthesized, specifically the double-decker silsesquioxane (DDSQ) cage structure (DDSQ-BZ). Comparative analyses were conducted between DDSQ-BZ monomers and the most commonly utilized bisphenol A-functionalized bifunctional benzoxazine (BPA-BZ) monomer. DDSQ-BZ compounds possess better thermal properties such as high char yield and high thermal decomposition temperature () after thermal ring-opening polymerization (ROP) because the inorganic DDSQ cage nanostructure features a nano-reinforcement effect.

Intrinsic functional connectivity correlates of cognitive deficits involving sustained attention and executive function in bipolar disorder.

Background: The neural correlate of cognitive deficits in bipolar disorder (BD) is an issue that warrants further investigation. However, relatively few studies have examined the intrinsic functional connectivity (FC) underlying cognitive deficits involving sustained attention and executive function at both the region and network levels, as well as the different relationships between connectivity patterns and cognitive performance, in BD patients and healthy controls (HCs).

Methods: Patients with BD (n = 59) and HCs (n = 52) underwent structural and resting-state functional magnetic resonance imaging and completed the Wisconsin Card Sorting Test (WCST), the continuous performance test and a clinical assessment.

Solid-State Nuclear Magnetic Resonance (SSNMR) Characterization of Osteoblasts From Mesenchymal Stromal Cell Differentiation to Osteoblast Mineralization.

Solid-state nuclear magnetic resonance (SSNMR), a technique capable of studying solid or semisolid biological samples, was first applied to study the cell differentiation and mineralization using the whole-cell sample. Mesenchymal stromal cells (MSCs) with multipotent differentiation capacity were induced to differentiate into osteoblasts. The whole differentiation process, osteoblast mineralization and the mineral maturation, was investigated using SSNMR, providing intact, atomic level information on the cellular mineral structural transformation.

Endogenous Lipid-GPR120 Signaling Modulates Pancreatic Islet Homeostasis to Different Extents.

Long-chain fatty acids (LCFAs) are not only energy sources but also serve as signaling molecules. GPR120, an LCFA receptor, plays key roles in maintaining metabolic homeostasis. However, whether endogenous ligand-GPR120 circuits exist and how such circuits function in pancreatic islets are unclear.

Autonomous sensing of the insulin peptide by an olfactory G protein-coupled receptor modulates glucose metabolism.

Along with functionally intact insulin, diabetes-associated insulin peptides are secreted by β cells. By screening the expression and functional characterization of olfactory receptors (ORs) in pancreatic islets, we identified Olfr109 as the receptor that detects insulin peptides. The engagement of one insulin peptide, insB:9-23, with Olfr109 diminished insulin secretion through Gi-cAMP signaling and promoted islet-resident macrophage proliferation through a β cell-macrophage circuit and a β-arrestin-1-mediated CCL2 pathway, as evidenced by β-arrestin-1 mouse models.

Solid-State NMR Studies of the Succinate-Acetate Permease from Citrobacter Koseri in Liposomes and Native Nanodiscs.

The succinate-acetate permease (SatP) is an anion channel with six transmembrane domains. It forms different oligomers, especially hexamers in the detergent as well as in the membrane. Solid-state NMR studies of SatP were carried out successfully on SatP complexes by reconstructing the protein into liposomes or retaining the protein in the native membrane of , where it was expressed.

An ionic lock and a hydrophobic zipper mediate the coupling between an insect pheromone receptor BmOR3 and downstream effectors.

Pheromone receptors (PRs) recognize specific pheromone compounds to guide the behavioral outputs of insects, which are the most diverse group of animals on earth. The activation of PRs is known to couple to the calcium permeability of their coreceptor (Orco) or putatively with G proteins; however, the underlying mechanisms of this process are not yet fully understood. Moreover, whether this transverse seven transmembrane domain (7TM)-containing receptor is able to couple to arrestin, a common effector for many conventional 7TM receptors, is unknown.

Anxiety symptom remission is associated with genetic variation of PTPRZ1 among patients with major depressive disorder treated with escitalopram.

Objectives: Genome-wide analyses of antidepressant response have suggested that genes initially associated with risk for schizophrenia may also serve as promising candidates for selective serotonin reuptake inhibitor (SSRI) efficacy. Protein tyrosine phosphatase, receptor-type, zeta-1 (PTPRZ1) has previously been shown to be associated with schizophrenia, but it has not been investigated as a predictor of antidepressant efficacy. The main objective of the study was to assess whether SSRI-mediated depressive and anxiety symptom remission in Chinese patients with major depressive disorder (MDD) are associated with specific PTPRZ1 variants.

Structural studies of phosphorylation-dependent interactions between the V2R receptor and arrestin-2.

Arrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor (GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail.

Weighted Gene Coexpression Network Analysis Reveals Essential Genes and Pathways in Bipolar Disorder.

Bipolar disorder (BD) is a major and highly heritable mental illness with severe psychosocial impairment, but its etiology and pathogenesis remains unclear. This study aimed to identify the essential pathways and genes involved in BD using weighted gene coexpression network analysis (WGCNA), a bioinformatic method studying the relationships between genes and phenotypes. Using two available BD gene expression datasets (GSE5388, GSE5389), we constructed a gene coexpression network and identified modules related to BD.

The amyloid structure of mouse RIPK3 (receptor interacting protein kinase 3) in cell necroptosis.

RIPK3 amyloid complex plays crucial roles during TNF-induced necroptosis and in response to immune defense in both human and mouse. Here, we have structurally characterized mouse RIPK3 homogeneous self-assembly using solid-state NMR, revealing a well-ordered N-shaped amyloid core structure featured with 3 parallel in-register β-sheets. This structure differs from previously published human RIPK1/RIPK3 hetero-amyloid complex structure, which adopted a serpentine fold.

NR4A1 counteracts JNK activation incurred by ER stress or ROS in pancreatic β-cells for protection.

Sustained hyperglycaemia and hyperlipidaemia incur endoplasmic reticulum stress (ER stress) and reactive oxygen species (ROS) overproduction in pancreatic β-cells. ER stress or ROS causes c-Jun N-terminal kinase (JNK) activation, and the activated JNK triggers apoptosis in different cells. Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an inducible multi-stress response factor.

DeSiphering receptor core-induced and ligand-dependent conformational changes in arrestin via genetic encoded trimethylsilyl H-NMR probe.

Characterization of the dynamic conformational changes in membrane protein signaling complexes by nuclear magnetic resonance (NMR) spectroscopy remains challenging. Here we report the site-specific incorporation of 4-trimethylsilyl phenylalanine (TMSiPhe) into proteins, through genetic code expansion. Crystallographic analysis revealed structural changes that reshaped the TMSiPhe-specific amino-acyl tRNA synthetase active site to selectively accommodate the trimethylsilyl (TMSi) group.

In vitro expansion of pancreatic islet clusters facilitated by hormones and chemicals.

Tissue regeneration, such as pancreatic islet tissue propagation in vitro, could serve as a promising strategy for diabetes therapy and personalised drug testing. However, such a strategy has not been realised yet. Propagation could be divided into two steps, in vitro expansion and repeated passaging.

Genetic variations in the ADCK1 gene predict paliperidone palmitate efficacy in Han Chinese patients with schizophrenia.

Genome-wide association study results have linked ADCK1 genetic variation with paliperidone efficacy in a European cohort. However, the generalizability of this locus to non-European populations is unknown. Han Chinese schizophrenia patients (n = 159) were treated with paliperidone palmitate and symptom severity was assessed over 3 months.

Spoof Surface Plasmon Polaritons Power Divider with large Isolation.

Periodic corrugated metal structure is designed to support and propagate spoof surface plasmon polaritons (SSPPs) wave in the microwave frequencies. In this paper, firstly a plasmonic waveguide consisting of oval-ring shaped cells is proposed with the performance of high transmission efficiency in a wide frequency range. The coplanar waveguides (CPWs) with 50 Ω impedance are adopted to feed the energies or extract signals at both ends of the plasmonic waveguide.

To Transfer or Not to Transfer? Development of a Dinitrosyl Iron Complex as a Nitroxyl Donor for the Nitroxylation of an Fe(III) -Porphyrin Center.

A positive myocardial inotropic effect achieved using HNO/NO(-) , compared with NO⋅, triggered attempts to explore novel nitroxyl donors for use in clinical applications in vascular and myocardial pharmacology. To develop M-NO complexes for nitroxyl chemistry and biology, modulation of direct nitroxyl-transfer reactivity of dinitrosyl iron complexes (DNICs) is investigated in this study using a Fe(III) -porphyrin complex and proteins as a specific probe. Stable dinuclear {Fe(NO)2 }(9) DNIC [Fe(μ-(Me) Pyr)(NO)2 ]2 was discovered as a potent nitroxyl donor for nitroxylation of Fe(III) -heme centers through an associative mechanism.