OP Model Research Articles

Internal consistency of multi-tier GW+EDMFT

The multi-tier GW+EDMFT scheme is an ab-initio method for calculating the electronic structure of correlated materials. While the approach is free from ad-hoc parameters, it requires a selection of appropriate energy windows for describing low-energy and strongly correlated physics. In this study, we test the consistency of the multi-tier description by considering different low-energy windows for a series of cubic SrXO3 (X = V, Cr, Mn) perovskites. Specifically, we compare the 3-orbital t2g model, the 5-orbital t2g + eg model, the 12-orbital t2g + Op model, and (in the case of SrVO3) the 14-orbital t2g + eg + Op model and compare the results to available photoemission and X-ray absorption measurements. The multi-tier method yields consistent results for the t2g and t2g + eg low-energy windows, while the models with Op states produce stronger correlation effects and mostly agree well with experiment, especially in the unoccupied part of the spectrum. We also discuss the consistency between the fermionic and bosonic spectral functions and the physical origin of satellite features, and present momentum-resolved charge susceptibilities.

Progress and Challenges in Developing Medical Countermeasures for Chemical, Biological, Radiological, and Nuclear Threat Agents.

This Commentary delves into the current progress and challenges on ongoing research on medical countermeasures (MCs) for chemical, biologic, radiologic, and nuclear (CBRN) threats. CBRN agents pose a serious risk to human health and safety, with the potential for mass casualties in both military and civilian settings. Chemical threats are toxic compounds that could be used in a terrorist attack, an accidental release, or chemical warfare. They include nerve agents, organophosphates, pulmonary agents, metabolic/cellular agents, vesicants, ocular toxicants, and opioid agents. Developing effective MCs is crucial for mitigating the acute and chronic effects of exposure to CBRN agents. The papers in this special issue of JPET highlights the latest advancements in MC research, showcasing insightful outcomes on experimental models, mechanisms, and translational research on MCs for CBRN threats. They portray several notable contributions, including the development of neurosteroid and combination anticonvulsant therapies for nerve agent poisoning, the exploration of chronic impacts and diagnostic tracers for OP neurotoxicity, the establishment of innovative pediatric OP models, the identification of novel molecules for ocular, pulmonary and vesicant injuries, and the repurposing of existing drugs for the treatment of botulism, cyanide, and OP poisoning. These crucial outcomes underscore the breadth of current research covering a variety of chemical threats. Overall, this collection of articles highlights the importance of ongoing research and development in the field of MCs, emphasizing the potential of these countermeasures to effectively treat and mitigate the effects of toxicant exposures and thereby enhance our preparedness for mass casualty incidents. SIGNIFICANCE STATEMENT: CBRN agents pose a significant threat to public health. Effective MCs exist for certain chemical threats, but there is a need for new and improved MCs for many others. The research presented in this special issue of JPET highlights the latest advancements in MCs for CBRN threats. This research has the potential to lead to the development of new and repurposed MCs that are more effective, broad-spectrum, and easier to administer to mitigate acute and long-term consequences of chemical exposures.

Aperiodicity, Star-freeness, and First-order Logic Definability of Operator Precedence Languages

A classic result in formal language theory is the equivalence among non-counting, or aperiodic, regular languages, and languages defined through star-free regular expressions, or first-order logic. Past attempts to extend this result beyond the realm of regular languages have met with difficulties: for instance it is known that star-free tree languages may violate the non-counting property and there are aperiodic tree languages that cannot be defined through first-order logic. We extend such classic equivalence results to a significant family of deterministic context-free languages, the operator-precedence languages (OPL), which strictly includes the widely investigated visibly pushdown, alias input-driven, family and other structured context-free languages. The OP model originated in the '60s for defining programming languages and is still used by high performance compilers; its rich algebraic properties have been investigated initially in connection with grammar learning and recently completed with further closure properties and with monadic second order logic definition. We introduce an extension of regular expressions, the OP-expressions (OPE) which define the OPLs and, under the star-free hypothesis, define first-order definable and non-counting OPLs. Then, we prove, through a fairly articulated grammar transformation, that aperiodic OPLs are first-order definable. Thus, the classic equivalence of star-freeness, aperiodicity, and first-order definability is established for the large and powerful class of OPLs. We argue that the same approach can be exploited to obtain analogous results for visibly pushdown languages too.

Evaluation of Midazolam-Ketamine-Allopregnanolone Combination Therapy against Cholinergic-Induced Status Epilepticus in Rats.

Status epilepticus (SE) is a life-threatening development of self-sustaining seizures that becomes resistant to benzodiazepines when treatment is delayed. Benzodiazepine pharmacoresistance is thought in part to result from internalization of synaptic GABAA receptors, which are the main target of the drug. The naturally occurring neurosteroid allopregnanolone is a therapy of interest against SE for its ability to modulate all isoforms of GABAA receptors. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been partially effective in combination with benzodiazepines in mitigating SE-associated neurotoxicity. In this study, allopregnanolone as an adjunct to midazolam or midazolam-ketamine combination therapy was evaluated for efficacy against cholinergic-induced SE. Adult male rats implanted with electroencephalographic (EEG) telemetry devices were exposed to the organophosphorus chemical (OP) soman (GD) and treated with an admix of atropine sulfate and HI-6 at 1 minute after exposure followed by midazolam, midazolam-allopregnanolone, or midazolam-ketamine-allopregnanolone 40 minutes after seizure onset. Neurodegeneration, neuronal loss, and neuroinflammation were assessed 2 weeks after GD exposure. Seizure activity, EEG power integral, and epileptogenesis were also compared among groups. Overall, midazolam-ketamine-allopregnanolone combination therapy was effective in reducing cholinergic-induced toxic signs and neuropathology, particularly in the thalamus and hippocampus. Higher dosage of allopregnanolone administered in combination with midazolam and ketamine was also effective in reducing EEG power integral and epileptogenesis. The current study reports that there is a promising potential of neurosteroids in combination with benzodiazepine and ketamine treatments in a GD model of SE. SIGNIFICANCE STATEMENT: Allopregnanolone, a naturally occurring neurosteroid, reduced pathologies associated with soman (GD) exposure such as epileptogenesis, neurodegeneration, and neuroinflammation, and suppressed GD-induced toxic signs when used as an adjunct to midazolam and ketamine in a delayed treatment model of soman-induced status epilepticus (SE) in rats. However, protection was incomplete, suggesting that further studies are needed to identify optimal combinations of antiseizure medications and routes of administration for maximal efficacy against cholinergic-induced SE.

Geniposide suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway

BackgroundOsteoporosis (OP), due to microarchitectural alterations, is associated with decreased bone mass, declined strength, and increased fracture risk. Increased osteoblast apoptosis contributes to the progression of OP. Natural compounds from herbs provide a rich resource for drug screening. Our previous investigation showed that geniposide (GEN), an effective compound from Eucommia ulmoides, could protect against the pathological development of OP induced by cholesterol accumulation.MethodsThe rat OP models were duplicated. Dual-energy X-ray absorptiometry, hematoxylin and eosin staining, and immunohistochemistry were used to evaluate bone changes. TUNEL/DAPI staining assays were used for cell apoptosis detection. Protein expression was determined by western blotting assays.ResultsA high-fat diet promoted OP development in vivo, and OX-LDL stimulated osteoblast apoptosis in vitro. GEN exhibited protective activities against OX-LDL-induced osteoblast apoptosis by increasing the NRF2 pathway and decreasing the NF-κB pathway. PDTC, an NF-κB inhibitor, could further promote the biological functions of GEN. In contrast, ML385, an NRF2 inhibitor, might eliminate GEN’s protection.ConclusionGEN suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway.

Evaluation of Biological Mechanisms of Quanduzhong Capsule for Treating Osteoporosis by Integrating Untargeted Metabolomics and Network Pharmacology

AbstractOsteoporosis (OP) is a metabolic disease characterized by bone formation and resorption disturbances. Quanduzhong Capsule (QDZC) is a common treatment for OP in China; however, the effective components and metabolites of the drug after oral administration remain largely unknown. This study aims to identify the active components, analyze the metabolite changes, and investigate the underlying mechanism against OP. In the study, ovariectomy-induced rat OP model was established, then treated with QDZC. Alendronate sodium tablets (ASTs) were used as a reference drug. The chemical constituents of QDZC were analyzed by UPLC-QTOF-MS (ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry) and network pharmacology. The metabolomics was used to analyze differences in serum metabolites of rats in different groups [Sham, Model, Model + QDZC, and Model + AST] at 4, 8, and 12 weeks. Body weight and bone mineral density (BMD) were assessed. Enzyme-linked immunosorbent assay was used to determine serum levels of Akt, p-Akt, ERK, and p-ERK. Our data suggested 86 different chemicals from QDZC, including nine core compounds. QDZC significantly regulated 25 biomarkers linked to arachidonic acid metabolism and unsaturated fatty acid biosynthesis, and promoted serum expression of Akt, p-Akt, ERK, and p-ERK. QDZC might act by activating PI3K-Akt and MAPK signaling pathways. In addition, QDZC may use arachidonic acid derivatives to inhibit osteoclast generation and bone resorption and enhance calcitriol formation to improve calcium absorption and increase bone mass.

Modelos de cálculo para a produtividade total dos fatores

A produtividade mede o nível de eficiência que uma economia apresenta em produzir bens e serviços. Assim, aumentar a produtividade é a maneira mais rápida de se atingir crescimento econômico e bem-estar social. Este estudo busca estimar e comprar quatro modelos diferentes para o cálculo da Produtividade Total dos Fatores (Total Factor Productivity - TFP). Os modelos escolhidos foram: Olley Pakes, 1996 - OP; Levinsohn Petrin, 2003 - LP; Wooldridge, 2009 - Wool; e, Ackerberg, Caves e Frazer, 2015 - ACF. Os resultados sugerem que o modelo ACF (2015) é um aprimoramento dos modelos OP e LP, além de apresentar resultados com significância estatística. O modelo Wool (2009) também é um aprimoramento e, novamente, apresenta resultados similares. Como o modelo ACF apresenta maior dispersão, o modelo Wool apresenta-se como a melhor escolha.

Identification of kukoamine a as an anti-osteoporosis drug target using network pharmacology and experiment verification

BackgroundOsteoporosis (OP) is a major and growing public health problem characterized by decreased bone mineral density and destroyed bone microarchitecture. Previous studies found that Lycium Chinense Mill (LC) has a potent role in inhibiting bone loss. Kukoamine A (KuA), a bioactive compound extract from LC was responsible for the anti-osteoporosis effect. This study aimed to investigate the anti-osteoporosis effect of KuA isolated from LC in treating OP and its potential molecular mechanism.MethodIn this study, network pharmacology and molecular docking were investigated firstly to find the active ingredients of LC such as KuA, and the target genes of OP by the TCMSP platform. The LC-OP-potential Target gene network was constructed by the STRING database and network maps were built by Cytoscape software. And then, the anti-osteoporotic effect of KuA in OVX-induced osteoporosis mice and MC3T3-E1 cell lines were investigated and the potential molecular mechanism including inflammation level, cell apoptosis, and oxidative stress was analyzed by dual-energy X-ray absorptiometry (DXA), micro-CT, ELISA, RT-PCR, and Western Blotting.ResultA total of 22 active compounds were screened, and we found KuA was identified as the highest active ingredient. Glycogen Phosphorylase (PYGM) was the target gene associated with a maximum number of active ingredients of LC and regulated KuA. In vivo, KuA treatment significantly increased the bone mineral density and improve bone microarchitecture for example increased BV/TV, Tb.N and Tb.Th but reduced Tb.Sp in tibia and lumber 4. Furthermore, KuA increased mRNA expression of osteoblastic differentiation-related genes in OVX mice and protects against OVX-induced cell apoptosis, oxidative stress level and inflammation level. In vitro, KuA significantly improves osteogenic differentiation and mineralization in cells experiment. In addition, KuA also attenuated inflammation levels, cell apoptosis, and oxidative stress level.ConclusionThe results suggest that KuA could protect against the development of OP in osteoblast cells and ovariectomized OP model mice and these found to provide a better understanding of the pharmacological activities of KuA again bone loss.

Morroniside ameliorates glucocorticoid-induced osteoporosis and promotes osteoblastogenesis by interacting with sodium-glucose cotransporter 2

Context Morroniside (MOR) possesses antiosteoporosis (OP) effects, but its molecular target and relevant mechanisms remain unknown. Objective We investigated the effects of MOR on glucocorticoid-induced OP and osteoblastogenesis and its underlying mechanisms. Materials and methods The effects of MOR (10–100 μM) on the proliferation and differentiation of MC3T3-E1 cells were studied in vitro. The glucocorticoid-induced zebrafish OP model was treated with 10, 20 and 40 μM MOR for five days to evaluate its effects on vertebral bone density and related osteogenic markers. In addition, molecular targets prediction and molecular docking analysis were carried out to explore the binding interactions of MOR with the target proteins. Results In cultured MC3T3-E1 cells, 20 μM MOR significantly increased cell viability (1.64 ± 0.12 vs. 0.95 ± 0.16; p < 0.01) and cell differentiation (1.57 ± 0.01 vs. 1.00 ± 0.04; p < 0.01) compared to the control group. MOR treatment significantly ameliorated vertebral bone loss in the glucocorticoid-induced OP zebrafish model (0.86 ± 0.02 vs. 0.40 ± 0.03; p < 0.01) and restored the expression of osteoblast-specific markers, including ALP, Runx2 and Col-І. Ligand-based target prediction and molecular docking revealed the binding interaction between MOR and the glucose pockets in sodium-glucose cotransporter 2 (SGLT2). Discussion and conclusions These findings demonstrated that MOR treatment promoted osteoblastogenesis and ameliorated glucocorticoid-induced OP by targeting SGLT2, which may provide therapeutic potential in managing glucocorticoid-induced OP.

How Commuting Time Affects Employees’ Income in China’s Urbanization Process

With the deepening of China’s urbanization, the commuting time of employees is increasing. Much evidence in Western developed countries supports the positive relationship between commuting time and income, but the relationship has not been verified in China. To determine whether the relationship is in effect in China, this paper constructs a theoretical model. From the perspective of long-term equilibrium analysis, the best choice for individuals is a hard-work strategy. The increase in long-term commuting time will eventually lead to individuals working harder, thus increasing personal income. The OP model established based on the survey data of Beijing residents’ time allocation in 2011, 2016, and 2021 also verified the positive impact of commuting time on employee income, which is more significant for groups with longer commuting time and shorter leisure time. The innovation of this paper has three parts. First, the long-term dynamic decision-making game was introduced into the personal choice model to reveal the long-term impact of commuting on income. Second, we verified the positive impact of commuting time on income in China. Third, we discussed the policy implications of increasing commuting time for improving urban operation efficiency in China’s urbanization process. Finally, it is suggested that the government should reasonably plan the urban functional structure and increase the construction of public transport in infrastructure, and enterprises should explore the staggered commuting system.

ZEB1 regulates bone metabolism in osteoporotic rats through inducing POLDIP2 transcription

BackgroundOsteoporosis (OP) is a common metabolic bone disease mainly involving bone remodeling and blood vessels. The current study aimed to explore the role of zinc finger E-box binding homeobox 1 (ZEB1) in OP.MethodsFirst, gene expression microarrays for OP were downloaded from the Gene Expression Omnibus database and analyzed to screen for potential targets. Subsequently, a rat OP model was constructed using ovariectomy (OVX), and osteoblastic and osteoclastic differentiation and alterations in osteoporotic symptoms were observed upon intraperitoneal injection of oe-ZEB1 lentiviral vectors. DNA polymerase delta interacting protein 2 (POLDIP2) was predicted to be a downstream target of ZEB1, which was validated by ChIP-qPCR and dual-luciferase experiments. RAW264.7 cells were subjected to lentiviral vector infection of oe-ZEB1 and/or sh-POLDIP2, followed by RANKL treatment to induce osteoclast differentiation.ResultsZEB1 was poorly expressed in blood samples of postmenopausal patients with OP and in bone tissues of OVX-treated rats. Overexpression of ZEB1 or POLDIP2 in OVX rats promoted osteoblastogenesis and inhibited osteoclast differentiation. In RANKL-treated RAW264.7 cells, the transcription factor ZEB1 enhanced the expression of POLDIP2, and silencing of POLDIP2 attenuated the inhibitory effect of oe-ZEB1 on the differentiation of macrophages RAW264.7 to osteoclasts.ConclusionsZEB1 promotes osteoblastogenesis and represses osteoclast differentiation, ultimately reducing the occurrence of postmenopausal OP by elevating the expression of POLDIP2.

Novel peptides extracted from Muraenesox cinereus bone promote calcium transport, osteoblast differentiation, and calcium absorption

Extracting peptides from fish bones as calcium supplements is of great significance for patients with osteoporosis. Novel peptides were obtained from Muraenesox cinereus bone (MCBP) by enzymatic hydrolysis and membrane separation. Molecular dynamics simulation and electron microscope analysis shown MCBP could chelate with calcium ions. A Caco-2 cell monolayer model was used to investigate the effect of peptide–calcium chelates on promoting calcium transport. MC3T3-E1 osteoblasts were treated with different concentrations of MCBP (0, 0.25, 0.5, or 1 mg/mL) to analyze the effects of MCBP on calcium absorption and cell differentiation factors. The bone formation of zebrafish evaluate the therapeutic effect of MCBP on the zebrafish OP model. The results showed that there were at least 13 kinds of calcium chelation modes in the mixed peptide, and peptide–calcium chelate could significantly improve calcium transport in the Caco-2 cell monolayer. After 14 days of culture with different concentrations of MCBP, the calcium deposition in MC3T3-E1 cells increased significantly. The type I collagen (COL-I), osteocalcin (OCN) and run-related transcription factor 2 (RUNX2), and activities of alkaline phosphatase (ALP) were dose-dependent with MCBP. MCBP can increase bone mineral density in an OP model of zebrafish. After being treated with MCBP, the expression levels of ALP, OCN, osteoprotegerin (OPG) and transforming growth factor-β (TGF-β) in the model group increased, while the expression levels of tartrate-resistant acid phosphatase (TRAP) decreased. The results indicated that MCBP may act as a nutritional food and provide an effective means for dietary supplementation in OP patients.

A machine learning approach to distinguishing between non-functioning and autonomous cortisol secreting adrenal incidentaloma on magnetic resonance imaging using texture analysis.

To investigate the possibility of distinguishing between nonfunctioning adrenal incidentalomas (NFAI) and autonomous cortisol secreting adrenal incidentalomas (ACSAI) with a model created with magnetic resonance imaging (MRI)-based radiomics and clinical features. In this study, 100 adrenal lesions were evaluated. The lesions were segmented on unenhanced T1-weighted in-phase (IP) and opposed-phase (OP) as well as on T2-weighted (T2-W) 3Tesla MRIs. The LASSO regression model was used to select potential predictors from 108 texture features for each sequence. Subsequently, a combined radiomics score and clinical features were created and compared. A significant difference was found between median rad-scores for ACSAI and NFAI in training and test sets (p < 0.05 for all sequences). Multivariate logistic regression analysis revealed that the length of the tumor (OR = 1.09, p = 0.007) was an independent risk factor related to ACSAI. Multivariate logistic regression analysis was used for building clinical-radiomics (combined) models. The Op, IP, and IP plus T2-W model had a higher performance with area under curve (AUC) 0.758, 0.746, and 0.721 on the test dataset, respectively. ACSAI can be distinguished from NFAI with high accuracy on unenhanced MRI. Radiomics analysis and the model constructed by machine learning algorithms seem superior to another radiologic assessment method. The inclusion of chemical shift MRI and the length of the tumor in the radiomics model could increase the power of the test.

Biomechanical investigation of intra-articular cage and cantilever technique in the treatment of congenital basilar invagination combined with atlantoaxial dislocation: a finite element analysis.

Biomechanical effect of posterior intra-articular cages and cantilever technique on the congenital basilar invagination (BI) combined with atlantoaxial dislocation (AAD) was investigated and evaluated using finite element (FE) analysis. A 3D nonlinear occipitocervical segment C0-C3 FE models of congenital BI and AAD was established. Then, the FE model treated with C2 pedicle screw and occipital plate fixation coupled with intra-articular cages (Cage + C2PS + OP) was compared to that without intra-articular cages (C2PS + OP). The range of motion (ROM) of C0C1-C2 and the maximum von Mises stresses (MVMS) on the intra-articular cages, screw-plate system, and C2 endplate were calculated and compared to furtheranalyze the stability of atlantoaxial joint and assess the collapse and fracture risks of intra-articular cages and screw-plate system. ROM of C0C1-C2 segment was reduced by 57.58%, 63.33%, 78.18%, and 75.90%, and the peak stresses of C2 pedicle screw and occipital plate were decreased by 84.86%, 72.90%, 73.24%, and 84.90% and 78.35%, 76.64%, 81.82%, and 89.49% for Cage + C2PS + OP model in flexion, extension, lateral bending, and axial rotation when compared with the C2PS + OP model under the same condition. The MVMS of intra-articular cages were 13.80MPa, 40.26MPa, 26.93MPa, and 17.50MPa and those of C2 endplate were 14.56MPa, 34.80MPa, 36.29MPa, and 37.56MPa in Cage + C2PS + OP model under same conditions. Posterior intra-articular cages and cantilever technique to treat BI-AAD can improve the stability of the atlantoaxial joint and reduce the risk of screw-plate breakage. The intra-articular cages can not only complement the height loss on account of atlantooccipital fusion but also provide stable support for posterior fixation fusion.

METTL3-m6 A methylase regulates the osteogenic potential of bone marrow mesenchymal stem cells in osteoporotic rats via the Wnt signalling pathway.

ObjectivesBone marrow mesenchymal stem cells (BMSCs) hold a high osteogenic differentiation potential, but the mechanisms that control the osteogenic ability of BMSCs from osteoporosis (OP‐BMSCs) need further research. The purpose of this experiment is to discuss the osteogenic effect of Mettl3 on OP‐BMSCs and explore new therapeutic target that can enhance the bone formation ability of OP‐BMSCs.Materials and MethodsThe bilateral ovariectomy (OVX) method was used to establish the SD rat OP model. Dot blots were used to reveal the different methylation levels of BMSCs and OP‐BMSCs. Lentiviral‐mediated overexpression of Mettl3 was applied in OP‐BMSCs. QPCR and WB detected the molecular changes of osteogenic‐related factors and Wnt signalling pathway in vitro experiment. The staining of calcium nodules and alkaline phosphatase detected the osteogenic ability of OP‐BMSCs. Micro‐CT and histological examination evaluated the osteogenesis of Mettl3 in OP rats in vivo.ResultsThe OP rat model was successfully established by OVX. Methylation levels and osteogenic potential of OP‐BMSCs were decreased in OP‐BMSCs. In vitro experiment, overexpression of Mettl3 could upregulate the osteogenic‐related factors and activate the Wnt signalling pathway in OP‐BMSCs. However, osteogenesis of OP‐BMSCs was weakened by treatment with the canonical Wnt inhibitor Dickkopf‐1. Micro‐CT showed that the Mettl3(+) group had an increased amount of new bone formation at 8 weeks. Moreover, the results of histological staining were the same as the micro‐CT results.ConclusionsTaken together, the methylation levels and osteogenic potential of OP‐BMSCs were decreased in OP‐BMSCs. In vitro and in vivo studies, overexpression of Mettl3 could partially rescue the decreased bone formation ability of OP‐BMSCs by the canonical Wnt signalling pathway. Therefore, Mettl3 may be a key targeted gene for bone generation and therapy of bone defects in OP patients.

New approach for local C-band weather radar precipitation calibration

Weather radar calibration is a topic of great current interest because it is useful for various hydrological applications. Several methods have been developed for adjusting the relation between reflectivity data Z and rainfall intensity R (Z/R) because droplet size distributions in different storm events are unknown and highly variable in time and space. The present study developed and tested a new space and time window-based procedure for optimal local calibration of weather radar using Z/R relations and applying it to convective and stratiform storms in the lower Grijalva river basin in Mexico. Improving rain estimates from the Sabancuy, Campeche radar is essential because it monitors this basin, which is prone to floods. The resulting estimates of the optimal power-law (Z = ARb) window-based procedure (OP) are compared with those of the default Marshall and Palmer (MP) relation using the observed rain gauge records. The appropriate window was selected using a criterion that considers factors affecting the free fall of raindrops. For most of the storms tested, metrics for the OP models showed better values than those calculated for the MP ones. The best MP performance is when using smooth calibration data, achieving similar metric results to that of the OP. The proposed observed calibration method could be useful to improve the default MP model estimates at any weather radar with similar characteristics to the ones analyzed in this work. The resulting Z/R relations could improve precipitation radar estimates for hydrologic model inputs.

Morusin induces osteogenic differentiation of bone marrow mesenchymal stem cells by canonical Wnt/\u03b2-catenin pathway and prevents bone loss in an ovariectomized rat model

BackgroundOsteoporosis (OP) is a metabolic bone disease due to the imbalance of osteogenesis and bone resorption, in which, bone marrow mesenchymal stem cells (BMSCs) have a significant effect as the seed cells. Recent research has shown the function of Morusin on inhibiting osteoclast differentiation in vitro. However, whether Morusin can regulate the osteogenic differentiation in addition to the proliferation of BMSCs remains unclear.MethodsBMSCs were isolated from 4-week-old Wistar rats and then treated with different concentrations of Morusin for 3, 5, 7, and 14 days. The proliferation of BMSCs was detected by MTT assay. The effect of Morusin on osteogenic differentiation of BMSCs was detected by RT-qPCR, Western blotting, ALP, and Alizarin Red staining. The effect of Morusin on Wnt/β-catenin signaling pathway was analyzed by RT-qPCR, Western blotting, and immunofluorescence. Finally, in the ovariectomy-induced osteoporosis model, the anti-osteoporosis activity of Morusin was determined by micro-CT, HE, and immunohistochemistry.ResultsThe results showed the function of 2.5–10 μM Morusin in the promotion of the proliferation in addition to osteogenic differentiation of BMSCs. Moreover, it also has an impact in activating the Wnt/β-catenin signaling pathway via inhibition of β-catenin phosphorylation as well as promotion of its nuclear translocation. Upon Dickkopf-related protein-1 (DKK-1, an inhibitor of the Wnt/β-catenin signaling pathway) was added to the Morusin, Morusin had a decreased stimulatory osteogenic effect on BMSCs. Finally, in the rat OP model, we found that Morusin could also exert anti-osteoporosis activity in vivo.ConclusionsThis study indicates the ability of Morusin in the promotion of osteogenic differentiation of BMSCs via the activation of Wnt/β-catenin signaling pathway and also shows the potential of Morusin to be an agent for osteoporosis treatment.

Trend analysis of reduced nitrogen components over the Netherlands with the EMEP4NL and OPS model

Declining ammonia emissions are not always reflected in ammonia concentrations due to physicochemical processes and meteorology. Here we present a trend analysis of reduced nitrogen components over the Netherlands using two different types of atmospheric transport models: the Eulerian grid model EMEP/MSC-W and the plume model OPS.We employ calculations with the Eulerian grid model EMEP/MSC-W for the Netherlands in its EMEP4NL configuration. Using the Weather Research Forecast (WRF) model as meteorological driver plus detailed emission data over the Netherlands as input into the EMEP4NL model, we present simulation results over the Netherlands of reduced nitrogen components from this model at a horizontal resolution of 1.3 × 2.1 km.Using this configuration of the EMEP/MSC-W model (EMEP4NL), a trend analysis is performed over the period 2006–2015 for concentration and deposition of reduced nitrogen components over the Netherlands. The same analysis is performed with the OPS-model, a plume model with a Lagrangian trajectory model for long range transport. Both models use the same MACC III emission distribution for countries outside of the Netherlands, and spatially more detailed emissions for the Netherlands itself. Emission totals per SNAP (Supporting National Action and Planning) sector per country are used over the period 2006–2015, according to the latest CEIP (Centre on Emissions Inventories and Projections) expert estimates. The OPS-model is driven with yearly specific meteorological fields provided by the Royal Netherlands Meteorological Institute (KNMI). Furthermore, the OPS-model parameterizes its chemistry, whereas EMEP4NL uses a state-of-the-art chemistry scheme.Results from ammonia concentrations, ammonium concentrations and wet deposition as calculated with both models, are first compared with observations from the National Air Quality Monitoring Network in the Netherland (LML). Calculations of ammonia and wet deposition both agree well with the measurements in the OPS and the EMEP4NL model. Ammonium is better represented by calculations with the EMEP4NL model than by the OPS-model. Measurements of dry deposition of reduced nitrogen are very limited, therefore only a comparison is made between the model results of EMEP4NL and OPS.Subsequently, a trend analysis is performed over the period 2006–2015 for the reduced nitrogen components for both model calculation results and the measurements. The trends of all components are calculated over the mean values of monitoring stations over the Netherlands. The reported decline in the emissions of ammonia is not reflected in the ammonia concentrations and wet deposition of reduced nitrogen as measured and calculated with the OPS and the EMEP4NL model. Ammonium concentrations on the other hand are declining (also) due to the decrease of the SOx emissions over the period 2006–2015. Finally, both models show a slight decline in the dry deposition values, despite the fact that both models (and observations) do not show a decrease in the ammonia concentrations. A more detailed analysis of the comparison of dry deposition of reduced nitrogen between both models, and the influence of the physicochemical processes and meteorology is in preparation. Overall, it is found that the calculated trends for the different reduced nitrogen components with a grid model like EMEP4NL and a plume model like OPS are roughly in line with each other.

Effects of retinoic acid-induced osteoporosis on pharmacokinetics and tissue distribution of 2,3,5,4'-tetrahydroxy stilbene-2-Ο-β-D-glucoside and β-ecdysterone in rats

Background: The compatibility of Radix Polygoni multiflori-Achyranthes (RPMA) root is a Traditional Chinese medicine pair frequently used in the clinic and has good anti-osteoporosis (OP) effects. Materials and Methods: The extract of the compatibility of RPMA root was given orally in this study. The pharmacokinetics and the distribution in the tissues of tetrahydroxystilbene glucoside and β-ecdysterone were considered by high-performance liquid chromatography in OP rats induced by retinoic acid and healthy rats. Quercetin was employed as the internal standard. According to the above results, the effects of Osteoporosis on the process of β-ecdysterone and 2,3,5,4'-tetrahydroxy stilbene 2-Ο-β-D-glucoside in rats were analyzed. Results: The results displayed that the peak time of β-ecdysterone in plasma of OP model rats was earlier and the plasma concentration and pharmacokinetic parameters of tetrahydroxystilbene glucoside in the model group were suggestively different from those in the normal group. The concentration distribution of the two components in each tissue of the model group was significantly diverse from that of the normal group. In particular, the concentrations of the two components in kidney tissue of the model group were inferior than those of the normal group at most time points. Conclusion: It is ventured that the two components may be convoluted in the treatment of OP. This experiment can deliver the reference for the further pharmacodynamic study of the compatibility of RPMA root and the correlation analysis of pharmacodynamics and the content of active ingredients in vivo.

Seismic analysis of the double-mode radial pulsator SX Phoenicis

ABSTRACT We present the results of complex seismic analysis of the prototype star SX Phoenicis. This analysis consists of a simultaneous fitting of the two radial-mode frequencies, the corresponding values of the bolometric flux amplitude (the parameter f) and of the intrinsic mode amplitude ε. The effects of various parameters as well as the opacity data are examined. With each opacity table it is possible to find seismic models that reproduce the two observed frequencies with masses allowed by evolutionary models appropriate for the observed values of the effective temperature and luminosity. All seismic models are in the post-main sequence phase. The OPAL and OP seismic models are in hydrogen shell-burning phase and the OPLIB seismic model has just finished an overall contraction and starts to burn hydrogen in a shell. The OP and OPLIB models are less likely due to the requirement of high initial hydrogen abundance (X0 = 0.75) and too high metallicity (Z ≈ 0.004) as for a Population II star. The fitting of the parameter f, whose empirical values are derived from multicolour photometric observations, provides constraints on the efficiency of convective transport in the outer layers of the star and on the microturbulent velocity in the atmosphere. Our complex seismic analysis with each opacity data indicates low to moderately efficient convection in the star’s envelope, described by the mixing length parameter of αMLT ∈ (0.0, 0.7), and the microturbulent velocity in the atmosphere of about ξt ∈ (4, 8) km s−1.