Effects of sitagliptin on blood glucose, lipids, pancreatic β cell secretory function and insulin resistance in patients with type 2 diabetes mellitus

Purpose: To study the influence of sitagliptin on blood glucose, lipid and pancreatic β cell function in type II diabetes mellitus (T2DM) patients.Methods: Two groups of T2DM patients (100/group) received either metformin only (control group), or metformin plus sitaglipin (study group) for 3 months. Blood lipid profiles, fasting blood glucose (FBG), indices of pancreatic function and insulin resistance were assayed using standard biochemical methods.Results: The metformin-sitaglipin combination resulted in significant decreases in FBG, 2-h PBG, HbAlc total cholesterol (TC), triacylglycerol, and low-density lipoprotein cholesterol (LDL-C), when compared with the metformin-only treatment (p < 0.05). Although there were significant decreases in pancreatic secretion of insulin, fasting insulin, and 2 h postprandial insulin in the two groups, these parameters were significantly lower in the metformin-only treated patients than in those with combination treatment (p < 0.05).Conclusion: Sitagliptin normalizes fasting blood glucose, lipid profiles and insulin secretion in type II diabetes mellitus (T2DM) patients.Keywords: Type 2 diabetes mellitus, Sitagliptin, Blood glucose, Pancreatic islet function, Insuli

Symmetry-protected higher-order exceptional points in staggered flatband rhombic lattices

Higher-order exceptional points (EPs), which appear as multifold degeneracies in the spectra of non-Hermitian systems, are garnering extensive attention in various multidisciplinary fields. However, constructing higher-order EPs still remains as a challenge due to the strict requirement of the system symmetries. Here we demonstrate that higher-order EPs can be judiciously fabricated in PT -symmetric staggered rhombic lattices by introducing not only on-site gain/loss but also nonHermitian couplings. Zero-energy flatbands persist and symmetry-protected third-order EPs (EP3) arise in these systems owing to the non-Hermitian chiral/sublattice symmetry, but distinct phase transitions and propagation dynamics occur. Specifically, the EP3 arises at the Brillouin zone (BZ) boundary in the presence of on-site gain/loss. The single-site excitations display an exponential power increase in the PT -broken phase. Meanwhile, a nearly flatband sustains when a small lattice perturbation is applied. For the lattices with non-Hermitian couplings, however, the EP3 appears at the BZ center. Quite remarkably, our analysis unveils a dynamical delocalization-localization transition for the excitation of the dispersive bands and a quartic power increase beyond the EP3. Our scheme provides a new platform towards the investigation of the higher-order EPs, and can be further extended to the study of topological phase transitions or nonlinear processes associated with higher-order EPs.Comment: 10 pages, 10 figure

LncRNA RP1-85F18.6 affects osteoblast cells by regulating the cell cycle

A lncRNA RP1-85F18.6 was reported to affect cell growth by regulating the cell cycle. Here we tested whether it affects the proliferation of osteoblast cells by regulating the cell cycle. We determined the expression of RP1-85F18.6 in two osteoblast cell lines hFOB and HOB by qPCR. Then we knocked down or overexpressed RP1-85F18.6 in hFOB and tested the alteration of viability, cell cycle, and cell cycle regulatory proteins. Results showed that both hFOB and HOB expressed RP1-85F18.6. The knockdown of RP1-85F18.6 decreased the viability of hFOB, while the overexpression of it increased the viability. Higher expression of RP1-85F18.6 results in higher cell viability. The knockdown of RP1-85F18.6 caused an increase in the S phase cells and a decrease in the G2/M phase cells. The overexpression of RP1-85F18.6 caused a decrease in the S phase cells and an increase in the G2/M phase cells. The knockdown of RP1-85F18.6 decreased cyclin A, cdk1, E2F, cyclin B, p53, and p21, whereas the overexpression of RP1-85F18.6 increased cyclin A, cdk1, E2F, cyclin B, p53, and p21. This study demonstrated that RP1-85F18.6 is expressed in osteoblast cell lines hFOB and HOB. RP1-85F18.6 affects the proliferation of osteoblasts by regulating the cell cycle

Wellbore Stability of a Deep-Water Shallow Hydrate Reservoir Based on Strain Softening Characteristics

Deep-sea hydrate has great commercial exploitation value as a new type of energy, due to huge reserves, wide distribution, cleanliness, and lack of pollution. Accurately, prediction of the mechanical properties of hydrate reservoirs is a key issue for safe and efficient exploitation of deep-sea hydrate. Although there have been some experimental and numerical simulation studies on the borehole stability of the hydrate layer, the influence of temperature and flow on the decomposition of reservoir hydrate is still not well understood. There have been few pure mechanical studies on the stress and strain state of the hydrate formation around the well, and it is impossible to intuitively understand the influence of the wellbore on the original stress state of the hydrate formation. This paper therefore uses a discrete element method to establish a deep-water shallow hydrate reservoir borehole stability model and compares the discrete element numerical model with an elastoplastic analytical model of borehole stability to verify the reliability of the numerical model. A simulation study on the influence of factors such as reservoir depth and hydrate saturation on wellbore stability is carried out. The simulation results effectively present the constitutive characteristics of strain softening of hydrate sediments. According to the different mechanical characteristics, the near-well zone can be divided into a plastic strain softening zone, a plastic strain hardening zone, and an elastic zone. Reservoir depth and hydrate saturation are found to change the stress state near the well. The greater the depth and the lower the hydrate saturation, the greater the borehole shrinkage. The diameter of the optimal horizontal well in the goaf is in the range from 0.6 to 1.2 m

Phylogenetic relationship and characterization of the complete mitochondrial genome of Colias fieldii (Lepidoptera: Papilionoidea: Pieridae)

Colias fieldii is a common seen diurnal butterflies in the fields and widely distributed in many provinces of China. In this study, we sequenced and analyzed the complete mitochondrial genome (mitogenome) of C. fieldii. This mitogenome was 15,150 bp long and encoded 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA unit genes (rRNAs). The overall base composition of the mitogenome was estimated to be A 39.8%, T 41.2%, C 11.4% and G 7.6%, with a high A + T content of 81.0%. Except for cox1 started with CGA, all other PCGs started with the standard ATN codons (seven ATG, four ATT and one ATC). Most of the PCGs terminated with the stop codon TAA or TAG, whereas cox1, cox2, nad5 and nad4 end with the incomplete codon T––. Phylogenetic analysis showed that C. fieldii is indeed the sister species of Colias erate with a high support value. All seven Coliadinae species formed one clade and was sister to Pierinae butterflies. Within Coliadinae, the relationships (Eurema + (Gonepteryx + (Catopsilia + Colias))) were highly supported

Graphene/tri-block copolymer composites prepared via RAFT polymerizations for dual controlled drug delivery via pH stimulation and biodegradation

A novel tri-block copolymer poly(oxopentanoate ethyl methacrylate)-block-poly(pyridyl disulfide ethyl acrylate)-block-poly(ethylene glycol acrylate) [poly(OEMA-b-PDEA-b-PEGA)], retaining active keto groups and pyridyl disulfide (PDS) side functionalities, was synthesized as a drug delivery vehicle using reversible addition-fragmentation chain transfer (RAFT) polymerization method. One mimic drug pyridine-2-thione (PT) was introduced into the monomer, PDEA for copolymerization. The other mimic drug O-benzylhydroxylamine (BHA) was conjugated with tri-block copolymer via efficient oxime coupling chemistry, followed by the attachment onto graphene via π-π stacking interaction to obtain a graphene/tri-block copolymer composite. 1H NMR, UV-vis absorption spectroscopy, fluorescence spectroscopy, gel permeation chromatography (GPC), atomic force microscope (AFM) and transmission electron microscope (TEM) were used to verify the successful step-wise preparation of the tri-block copolymer and drug loaded composite. In vitro release behaviors of BHA and PT from graphene/tri-block copolymer composite via dual drug release mechanisms were investigated. BHA can be released under acid environment, while PT will be released in the presence of reducing agents, such as dithiothreitol (DTT) or glutathione (GSH). It can be envisioned that this novel composite could be exploited as a novel intracellular drug delivery system via dual release mechanisms

Ontology-based assembly knowledge representation and process file generation

Aiming at the problems of low assembly knowledge shareability and reusability as well as long generation cycle of assembly process, this paper proposes an ontology-based assembly knowledge representation method, and generates assembly process file based on this method. The assembly ontology, modelling through protégé software, has three central classes: AssemblyObject, AssemblyElement, and AssemblyTool. The assembly ontology is described in OWL language and the assembly knowledge concepts including classes and individuals are linked through properties. In addition, the assembly ontology in OWL language is parsed through Python's RDFLib library, and it is called and displayed in LabVIEW. Finally, the assembly process file containing assembly sequence and assembly process parameters is generated. This method realizes the formal description of assembly process knowledge at the semantic level and improves the shareability and reusability of assembly knowledge. Besides, the corresponding assembly process knowledge can be quickly queried and obtained through this method, improving the efficiency of assembly process planning, and providing intelligent assembly basic knowledge

U2AF2-SNORA68 promotes triple-negative breast cancer stemness through the translocation of RPL23 from nucleoplasm to nucleolus and c-Myc expression

Abstract Background Small nucleolar RNAs (snoRNAs) play key roles in ribosome biosynthesis. However, the mechanism by which snoRNAs regulate cancer stemness remains to be fully elucidated. Methods SNORA68 expression was evaluated in breast cancer tissues by in situ hybridization and qRT‒PCR. Proliferation, migration, apoptosis and stemness analyses were used to determine the role of SNORA68 in carcinogenesis and stemness maintenance. Mechanistically, RNA pull-down, RNA immunoprecipitation (RIP), cell fractionation and coimmunoprecipitation assays were conducted. Results SNORA68 exhibited high expression in triple-negative breast cancer (TNBC) and was significantly correlated with tumor size (P = 0.048), ki-67 level (P = 0.037), and TNM stage (P = 0.015). The plasma SNORA68 concentration was significantly lower in patients who achieved clinical benefit. The SNORA68-high patients had significantly shorter disease-free survival (DFS) (P = 0.036). Functionally, SNORA68 was found to promote the cell stemness and carcinogenesis of TNBC in vitro and in vivo. Furthermore, elevated SNORA68 expression led to increased nucleolar RPL23 expression and retained RPL23 in the nucleolus by binding U2AF2. RPL23 in the nucleolus subsequently upregulated c-Myc expression. This pathway was validated using a xenograft model. Conclusion U2AF2-SNORA68 promotes TNBC stemness by retaining RPL23 in the nucleolus and increasing c-Myc expression, which provides new insight into the regulatory mechanism of stemness

Effects of Copper Exposure on Oxidative Stress, Apoptosis, Endoplasmic Reticulum Stress, Autophagy and Immune Response in Different Tissues of Chinese Mitten Crab (<i>Eriocheir sinensis</i>)

High concentrations of copper (Cu2+) pose a great threat to aquatic animals. However, the mechanisms underlying the response of crustaceans to Cu2+ exposure have not been well studied. Therefore, we investigated the alterations of physiological and molecular parameters in Chinese mitten crab (Eriocheir sinensis) after Cu2+ exposure. The crabs were exposed to 0 (control), 0.04, 0.18, and 0.70 mg/L of Cu2+ for 5 days, and the hemolymph, hepatopancreas, gills, and muscle were sampled. The results showed that Cu2+ exposure decreased the antioxidative capacity and promoted lipid peroxidation in different tissues. Apoptosis was induced by Cu2+ exposure, and this activation was associated with the mitochondrial and ERK pathways in the hepatopancreas. ER stress-related genes were upregulated in the hepatopancreas but downregulated in the gills at higher doses of Cu2+. Autophagy was considerably influenced by Cu2+ exposure, as evidenced by the upregulation of autophagy-related genes in the hepatopancreas and gills. Cu2+ exposure also caused an immune response in different tissues, especially the hepatopancreas, where the TLR2-MyD88-NF-κB pathway was initiated to mediate the inflammatory response. Overall, our results suggest that Cu2+ exposure induces oxidative stress, ER stress, apoptosis, autophagy, and immune response in E. sinensis, and the toxicity may be implicated following the activation of the ERK, AMPK, and TLR2-MyD88-NF-κB pathways

A nitrogenous pre-intercalation strategy for the synthesis of nitrogen-doped Ti<inf>3</inf>C<inf>2</inf>T<inf>x</inf>MXene with enhanced electrochemical capacitance

A two-step pre-intercalation strategy is developed, using ammonium citrate as an all-in-one intercalant, antioxidant and nitrogen source, for producing nitrogen-doped Ti3C2Tx MXene with improved electrochemical capacitance and high-rate performance.</p