M1 M5 Research Articles

Nanocrystalline Iron Oxides with Various Average Crystallite Size Investigated Using Magnetic Resonance Method

A series of nanocrystalline iron oxide samples (M1–M5) which differ from each other in average crystallite size (from 26 to 37 nm) was studied. The raw material was nanocrystalline iron with an average crystallite size equal to 21 nm promoted with hardly reducible oxides: Al2O3, CaO, K2O (in total, max. 10 wt%). Nanocrystalline iron was subjected to oxidation with water vapor to achieve different oxidation degrees (α = 0.16–1.00). Metallic iron remaining in the samples after the oxidizing step was removed by etching. Magnetic resonance spectra of all samples were obtained at room temperature. All resonance lines were asymmetric and intense. These spectra were fitted by Lorentzian and Gaussian functions. All spectral parameters depend on the preparation method of the nanoparticles. We suppose that the Lorentz fit gives us a spectrum from larger agglomerated sizes whereas the Gaussian fit comes from much smaller magnetic centers. For the nanocrystalline samples with the largest size of iron oxide nanocrystallites, the highest value of total integrated intensity was obtained, indicating that at smaller sizes, they are more mobile in reorientation processes resulting in more settings of anti-parallel magnetic moments. The magnetic anisotropy should also increase with the increase in size of nanocrystallites.

Antiemetic activity of abietic acid possibly through the 5HT3 and muscarinic receptors interaction pathways

The present study was designed to evaluate the antiemetic activity of abietic acid (AA) using in vivo and in silico studies. To assess the effect, doses of 50 mg/kg b.w. copper sulfate (CuSO4⋅5H2O) were given orally to 2-day-old chicks. The test compound (AA) was given orally at two doses of 20 and 40 mg/kg b.w. On the other hand, aprepitant (16 mg/kg), domperidone (6 mg/kg), diphenhydramine (10 mg/kg), hyoscine (21 mg/kg), and ondansetron (5 mg/kg) were administered orally as positive controls (PCs). The vehicle was used as a control group. Combination therapies with the referral drugs were also given to three separate groups of animals to see the synergistic and antagonizing activity of the test compound. Molecular docking and visualization of ligand-receptor interaction were performed using different computational tools against various emesis-inducing receptors (D2, D3, 5HT3, H1, and M1–M5). Furthermore, the pharmacokinetics and toxicity properties of the selected ligands were predicted by using the SwissADME and Protox-II online servers. Findings indicated that AA dose-dependently enhances the latency of emetic retching and reduces the number of retching compared to the vehicle group. Among the different treatments, animals treated with AA (40 mg/kg) exhibited the highest latency (98 ± 2.44 s) and reduced the number of retching (11.66 ± 2.52 times) compared to the control groups. Additionally, the molecular docking study indicated that AA exhibits the highest binding affinity (− 10.2 kcal/mol) toward the M4 receptors and an elevated binding affinity toward the receptors 5HT3 (− 8.1 kcal/mol), M1 (− 7.7 kcal/mol), M2 (− 8.7 kcal/mol), and H1 (− 8.5 kcal/mol) than the referral ligands. Taken together, our study suggests that AA has potent antiemetic effects by interacting with the 5TH3 and muscarinic receptor interaction pathways. However, additional extensive pre-clinical and clinical studies are required to evaluate the efficacy and toxicity of AA.

Experimental Study on Chrome Tanned Leather Shavings Modification—Properties and Prospective for Future Application

Chrome tanned leather shavings (CTLS) are considered one of the more difficult wastes to manage in the tanning industry. At the same time, this waste is an important source of good quality collagen. The few methods described in the literature for the valorization of these wastes usually require pre-treatment or activation. In this study, an attempt was made to see if raw chrome tanned leather shavings (CTLS) could be modified to obtain secondary raw materials with new physical properties. Glutaraldehyde, glycerol, EDCs, pectin, and tannins were selected for modification of the CTLS. The effectiveness of the processes carried out was confirmed by FTIR analysis of the materials obtained. Changes in the intensity of the characteristic collagen peak (amide I, amide II, and amide III) and changes in the position of the bands in the 1200–1000 cm−1 region were observed in the recorded spectra. The modifications introduced confirmed changes in the physical properties of samples M1–M5, including an increase in bulk density from 0.15 to 0.59 g cm−3, and improved tensile strength is some cases. The elemental content results of the samples tested showed the resulting modified CTLS were free of Cd, Hg, Pb, and Cr(VI). It was also confirmed tanning waste contained significant amounts of various valuable elements. The research also included preliminary tests to assess the environmental impact of the modified materials. In a phytotoxicity test conducted on modified CTLS, M1 with pectins showed the highest root stimulation (105%), while samples with glutaraldehyde and unmodified CTLS showed significant root inhibition (75%, 74%). Other samples showed moderate plant toxicity and seed germination was not significantly affected.

Aggregation-enhanced emission and multicolored electrochromic behavior of polyphenyl benzoates

By functionalizing various polyphenyl with ester groups, five kinds of polyphenyl benzoates based electrochromic materials (M1–M5) are synthesized and characterized. These materials show typical aggregation-induced emission and aggregation-enhanced emission in...

Estimation of cohesion for intact rock materials using regression and soft computing analyses

Shear strength parameters such as cohesion (c) and internal friction angle (ϕ) are among the most critical rock properties used in the geotechnical design of most engineering projects. However, the determination of these properties is laboring and requires special equipment. Therefore, this study introduces several predictive models based on regression and artificial intelligence methods to estimate the c of different rock types. For this purpose, a comprehensive literature survey is carried out to collect quantitative data on the shear strength properties of different rock types. Then, regression and soft computing analyses are performed to establish several predictive models based on the collected data. As a result of these analyses, five different predictive models (M1–M5) were established. Based on the performance of the established predictive models, the artificial neural network-based predictive model (model 5, M5) was the most suitable choice for evaluating the c for different rock types. In addition, mathematical expressions behind the M5 model are also presented in this study to allow users to implement it more efficiently. In this regard, the present study can be declared a case study showing the applicability of regression and soft computing analyses to evaluate the c of different rock types. However, the number of datasets used in this study should be increased to get more comprehensive predictive models in future studies.

Crystal Structure, Thermal Expansion and Luminescence of Ca10.5−xNix(VO4)7

The structural and luminescence properties of a new material, Ca10.5−xNix(VO4)7, formed by substitution of a fraction of calcium by nickel, are studied as a function of the Ni content (x). The powder X-ray diffraction results for the polycrystals, synthesized using a solid-state reaction method, show that in the studied temperature range (300–1150 K), the structure of the unsubstituted material (space group R3c, whitlockite-β-Ca3(PO4)2 structure type) is conserved up to the solubility limit, x = 0.72(2), determined on the basis of variation of unit cell size with x. The samples of nominal composition exceeding this limit contain a significant amount of the impurity phase.The structural refinements demonstrate that Ni atoms preferentially occupy the M5 site (one of the five independent Ca sites, M1–M5). The unit cell size was equally studied in the range of 300–1150 K, leading to the determination of the thermal expansion coefficients. It was found that with rising Ni content, the room temperature volumetric thermal expansion decreases from 41.80 MK−1 (x = 0.16) to 39.24 MK−1 (x = 0.66) and to 38.92 MK−1 at the solubility limit, this reduction being in line with earlier reported data for x=0. In the unit cell variation, around 800–900 K, a weak anomaly is observed, detectable most clearly for the axial ratio; it is also visible at thermal expansion coefficient temperature dependence. Substitution of Ca by Ni ions reduces the optical band gap of Ca10.5−xNix(VO4)7 from 3.56 (x = 0) to 3.29 and 3.16 eV observed for Ni-containing samples (x = 0.33 and 0.66, respectively). Observed bands in the absorption and photoluminescence spectra are assigned to electronic transitions in both VO43− groups and Ni2+ ions, confirming that Ni mainly occupies the M5 site. The band gap narrowing and decrease in photoluminescence intensity when the Ni concentration increases makes Ni-substituted compounds attractive for application, e.g., as photocatalysts.

Self‐assembled neutral and ionic [2 + 2] metallomacrocycles using a new flexible ditopic Pt(II)‐based organometallic tecton bearing a pyrimidine motif: Facile syntheses and enhanced anticancer potency

A new di‐platinum(II) organometallic compound (3) has been synthesized from a readily available pyrimidine derivative in two steps. 3 is a conformationally flexible molecule due to the presence of ethereal linkages. The application of 3 as an acceptor tecton in supramolecular chemistry was explored using coordination‐driven self‐assembly protocol. Thus, three neutral (M1–M3) and two ionic (M4 and M5) metallomacrocycles were obtained in high yields, the structures of which included biologically active pyrimidine and π‐conjugated trans‐Pt(II)‐alkynyl motifs. Formation of these five flexible [2 + 2] ensembles (M1–M5) was confirmed using FT‐IR and NMR spectroscopy (1H, 31P{1H}, 13C{1H}, and 1H DOSY) as well as HRMS experiments. DFT calculations suggest that the macrocycles have nano‐scalar dimensions with well‐defined cavities. Cytotoxicity of 3 and macrocycles (M1–M5) were estimated against A549 human lung cancer cell line. Results indicate improvement in cytotoxicity upon self‐assembly of 3 with neutral and ionic donor tectons to yield, respectively ionic and neutral macrocycles (M1–M5). Although the organometallic molecule 3 is almost seven times more potent than cisplatin, the antiproliferative potencies of the macrocycles (M1–M5) are up to 17 times better than cisplatin. Annexin V‐FITC assay studies show that post‐treatment with the organometallic 3, or the macrocycles (M1–M5), the A549 cancer cells are present in the early apoptosis stage.

Introductory Engineering Mathematics Students’ Weighted Score Predictions Utilising a Novel Multivariate Adaptive Regression Spline Model

Introductory Engineering Mathematics (a skill builder for engineers) involves developing problem-solving attributes throughout the teaching period. Therefore, the prediction of students’ final course grades with continuous assessment marks is a useful toolkit for degree program educators. Predictive models are practical tools used to evaluate the effectiveness of teaching as well as assessing the students’ progression and implementing interventions for the best learning outcomes. This study develops a novel multivariate adaptive regression spline (MARS) model to predict the weighted score WS (i.e., the course grade). To construct the proposed MARS model, Introductory Engineering Mathematics performance data over five years from the University of Southern Queensland, Australia, were used to design predictive models using input predictors of online quizzes, written assignments, and examination scores. About 60% of randomised predictor grade data were applied to train the model (with 25% of the training set used for validation) and 40% to test the model. Based on the cross-correlation of inputs vs. the WS, 12 distinct combinations with single (i.e., M1–M5) and multiple (M6–M12) features were created to assess the influence of each on the WS with results bench-marked via a decision tree regression (DTR), kernel ridge regression (KRR), and a k-nearest neighbour (KNN) model. The influence of each predictor on WS clearly showed that online quizzes provide the least contribution. However, the MARS model improved dramatically by including written assignments and examination scores. The research demonstrates the merits of the proposed MARS model in uncovering relationships among continuous learning variables, which also provides a distinct advantage to educators in developing early intervention and moderating their teaching by predicting the performance of students ahead of final outcome for a course. The findings and future application have significant practical implications in teaching and learning interventions or planning aimed to improve graduate outcomes in undergraduate engineering program cohorts.

Comprehensive Metabolic Profiling of Euphorbiasteroid in Rats by Integrating UPLC-Q/TOF-MS and NMR as Well as Microbial Biotransformation.

Euphorbiasteroid, a lathyrane-type diterpene from Euphorbiae semen (the seeds of Euphorbia lathyris L.), has been shown to have a variety of pharmacological effects such as anti-tumor and anti-obesity. This study aims to investigate the metabolic profiles of euphorbiasteroid in rats and rat liver microsomes (RLMs) and Cunninghamella elegans bio-110930 by integrating ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS), UNIFI software, and NMR techniques. A total of 31 metabolites were identified in rats. Twelve metabolites (M1–M5, M8, M12–M13, M16, M24–M25, and M29) were matched to the metabolites obtained by RLMs incubation and the microbial transformation of C. elegans bio-110930 and their structures were exactly determined through analysis of NMR spectroscopic data. In addition, the metabolic pathways of euphorbiasteroid were then clarified, mainly including hydroxylation, hydrolysis, oxygenation, sulfonation, and glycosylation. Finally, three metabolites, M3 (20-hydroxyl euphorbiasteroid), M24 (epoxylathyrol) and M25 (15-deacetyl euphorbiasteroid), showed significant cytotoxicity against four human cell lines with IC50 values from 3.60 μM to 40.74 μM. This is the first systematic investigation into the in vivo metabolic pathways of euphorbiasteroid and the cytotoxicity of its metabolites, which will be beneficial for better predicting the metabolism profile of euphorbiasteroid in humans and understanding its possible toxic material basis.

Metabolites Analysis of Anti-Myocardial Ischemia Active Components of Saussurea involucrata Based on Gut Microbiota-Drug Interaction.

Saussurea involucrata has been reported to have potential therapeutic effects against myocardial ischemia. The pharmacological effects of oral natural medicines may be influenced by the participation of gut microbiota. In this study, we aimed to investigate the bidirectional regulation of gut microbiota and the main components of Saussurea involucrata. We first established a quantitative method for the four main components (chlorogenic acid, syringin, acanthoside B, rutin) which were chosen by fingerprint using liquid chromatography tandem mass spectrometry (LC-MS/MS), and found that gut microbiota has a strong metabolic effect on them. Meanwhile, we identified five major rat gut microbiota metabolites (M1–M5) using liquid chromatography tandem time-of-flight mass spectrometry (LC/MSn-IT-TOF). The metabolic properties of metabolites in vitro were preliminarily elucidated by LC-MS/MS for the first time. These five metabolites of Saussurea involucrata may all have potential contributions to the treatment of myocardial ischemia. Furthermore, the four main components (10 μg/mL) can significantly stimulate intestinal bacteria to produce short chain fatty acids in vitro, respectively, which can further contribute to the effect in myocardial ischemia. In this study, the therapeutic effect against myocardial ischemia of Saussurea involucrata was first reported to be related to the intestinal flora, which can be useful in understanding the effective substances of Saussurea involucrata.

Survey of immunopharmacological effects of botulinum toxin in cell signaling of bronchial smooth muscle cells in allergic asthma.

Asthma is a lung disease that has influenced more than 350 million people worldwide. Airway smooth muscle (ASM) spasm leads to airway hyperresponsiveness (AHR) and bronchial obstruction, which are clinical manifestations of an asthma attack. Botulinum toxin (BTX) is a bacteria toxin that acts as muscle relaxant and may have therapeutic effects on AHR and asthma. In this study, the effect of BTX on AHR and related gene expressions was evaluated. An asthma mice model was developed which was treated with BTX in two ways: intranasally (IN) and via nebulization (N) (0.01, 0.1, and 1 U/mL and 10 U/mL, respectively) on days 25, 27 and 29. AHR was evaluated on days 24, 26, 28, and 30, and gene expressions were evaluated for TrkA, TrkB, M1-M5, α7nAChR, TNF-α, and extracellular signal-regulated kinase 2 (ERK2) proteins. For histopathology of the lungs, perivascular and peribronchial inflammation, production of mucus, and goblet cell hyperplasia were studied. On day 24, treatment with BTX (for all doses) had no significant effect on AHR, but on days 26 and 28, AHR was decreased and this continued up to day 30 for all treated groups. Treatment with BTX had no significant effect on the gene expressions of TrkA, TrkB, M1-M5, α7nAChR, TNF-α, and ERK2 proteins, perivascular inflammation, peribronchial inflammation, hyperplasia of the goblet cell and production of mucus. Besides, mice administered with 10 mg/mL BTX perished. The BTX therapy controlled asthma attacks by decreasing AHR and relaxation of ASMs. However, BTX had no significant effect on airway inflammation and production of mucus. While using BTX, it is necessary to prescribe safe doses in order to prevent adverse reactions.

Advancing the Development of Recyclable Aromatic Polyesters by Functionalization and Stereocomplexation

AbstractThe development of innovative synthetic polymer systems to overcome the trade‐offs between the polymer's depolymerizability and performance properties is in high demand for advanced material applications and sustainable development. In this contribution, we prepared a class of aromatic cyclic esters (M1–M5) from thiosalicylic acid and epoxides by facile one‐pot synthesis. Ring‐opening polymerization of Ms afforded aromatic polyesters P(M)s with high molecular weights and narrow dispersities. The physical and mechanical properties of P(M)s can be modulated by stereocomplexation and regulation of the side‐chain flexibility of the polymers, ultimately achieving high‐performance properties such as high thermal stability and crystallinity (Tm up to 209 °C), as well as polyolefin‐like high mechanical strength, ductility, and toughness. Furthermore, the functionalizable moieties of P(M)s have driven a wide array of post‐polymerization modifications toward access to value‐added materials. More importantly, the P(M)s were able to selectively depolymerize into monomers in excellent yields, thus establishing its circular life cycle.

Feeding Frequency Modulates the Intestinal Transcriptome Without Affecting the Gut Microbiota in Pigs With the Same Daily Feed Intake.

The objective of this study was to elucidate the impacts of irregular eating patterns on gut microbiota and transcriptomic responses in a pig model with different feeding regimens. The experiment involved 24 growing pigs (Duroc × Landrace × Large White, 48 days of age) which were randomly allocated to one of three feeding patterns: one-meal (M1), three-meals (M3), or five-meals (M5) per day with the same daily feed intake. The results showed that different feeding frequencies had no significant effects on the microbial composition of ileal digesta, colonic digesta, colon mucosa, as well as the concentration of SCFAs in colonic digesta. Mucosa transcriptomic profiling data showed the pathways related to vitamin metabolism were enriched in the ileum and colon of pigs in the pairwise comparison between M3 and M1 groups. On the other hand, the pathways related to lipid metabolism were enriched in the ileum and colon of pigs in the pairwise comparison between M5 and M1 groups. Lastly, the pathways related to protein metabolism were enriched in the colon in the pairwise comparison between M3 and M1 groups, M5 and M1 groups, M5 and M3 groups, while the ileum was not enriched. Differentially expressed genes (DEG) related to metabolism showed that carbohydrate transport was suppressed in the ileum and enhanced in the colon in M5 and M3 groups compared with the M1 group. Compared with the M3 group, carbohydrate transport in the ileum was enhanced in the M5 group, while in the colon was inhibited. With the increase of feeding frequency, the catabolism, biosynthesis, and transport of lipid in the ileum were suppressed, while those in the colon were enhanced. Compared with the M1 group, amino acid transport in the ileum and colon in the M3 group was enhanced. Amino acid catabolism in the ileum in the M5 group was enhanced compared with M1 and M3 groups. In summary, different feeding frequencies affected the transport of carbohydrate, lipid, and amino acid in the ileum and colon, and affected the catabolism and biosynthesis of lipid in the ileum and colon with a low impact on intestinal microbiota.

Aged Mice Devoid of the M3 Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease.

The parasympathetic nervous system is critically involved in the regulation of tear secretion by activating muscarinic acetylcholine receptors. Hence, various animal models targeting parasympathetic signaling have been developed to induce dry eye disease (DED). However, the muscarinic receptor subtype (M1–M5) mediating tear secretion remains to be determined. This study was conducted to test the hypothesis that the M3 receptor subtype regulates tear secretion and to evaluate the ocular surface phenotype of mice with targeted disruption of the M3 receptor (M3R−/−). The experimental techniques included quantification of tear production, fluorescein staining of the ocular surface, environmental scanning electron microscopy, assessment of proliferating cells in the corneal epithelium and of goblet cells in the conjunctiva, quantification of mRNA for inflammatory cytokines and prooxidant redox enzymes and quantification of reactive oxygen species. Tear volume was reduced in M3R−/− mice compared to age-matched controls at the age of 3 months and 15 months, respectively. This was associated with mild corneal epitheliopathy in the 15-month-old but not in the 3-month-old M3R−/− mice. M3R−/− mice at the age of 15 months also displayed changes in corneal epithelial cell texture, reduced conjunctival goblet cell density, oxidative stress and elevated mRNA expression levels for inflammatory cytokines and prooxidant redox enzymes. The findings suggest that the M3 receptor plays a pivotal role in tear production and its absence leads to ocular surface changes typical for DED at advanced age.

Antibacterial and Anti-Inflammatory Potential of Mouthwash Composition Based on Natural Extracts

Mouthwash contains chlorhexidine, triclosan, cetylpyridinium chloride, benzethonium chloride, and fluoride. However, continuous use of these chemical substance affects both pathogenic and nonpathogenic oral bacteria and causes an imbalance in the oral environment, which is known to affect not only oral diseases but also systemic diseases. Therefore, in this study, we observed the possibility of replacing the composition of chemical compound mouthwash with a natural extract. Platycodon grandiflorum (PG), Chaenomeles sinensis Koehne (CSK), and Siraitia grosvenorii (SG) were used as natural extracts, and a mixture of enzyme salt, xylitol, mint, green tea, lemon, and propolis were used as the natural extract mixture series (M1–M5). The natural extracts and natural mixture series were evaluated for the antibacterial effect, anti-inflammatory effect, cell viability, and nitric oxide (NO) assay using eleven types of pathogenic oral bacteria, two types of nonpathogenic oral bacteria, and macrophages RAW 264.7 cells. Cell viability was measured as about 35.9–46.7% for the control group (GA and LIS), about 36.3–57.7% for the natural extract group (PG, CSK, SG), and about 95.8–97.9% for the natural extract mixture series group (M1–M5). In the NO assay tested with lipopolysaccharide (LPS)-stimulated inflammatory responses, the control group was measured at about 89%, the natural extracts group were measured at 84–88%, and the natural extract mixture series group at about 54–82%. It was observed that some natural extracts (PG, SG) and natural extract mixtures (M4, M5) inhibited LPS-induced NO production, which meant that natural extracts had anti-inflammation potential. In conclusion, it was observed that natural extracts mixed in proper proportions affect pathogenic oral bacteria and not nonpathogenic oral bacteria. It is considered that appropriately formulated natural extracts can maintain a healthy oral environment and further replace commercial mouthwash based on chemical compound mixtures.

Metabolic study of ginsenoside Rg3 and glimepiride in type 2 diabetic rats by liquid chromatography coupled with quadrupole‐Orbitrap mass spectrometry

RationaleGinsenoside Rg3 and glimepiride have been applied to treat type 2 diabetes (T2DM) because of their good hypoglycemic effects. In this study, the effects of ginsenoside Rg3 acting synergistically with glimepiride were investigated in liver microsomes from rats with type 2 diabetes.MethodsAn in vitro incubation system with normal rat liver microsomes (RLM) and type 2 diabetic rat liver microsomes (TRLM) was developed. The system also included two experimental groups consisting of RLM and TRLM pretreated with ginsenoside Rg3 and glimepiride (named the RLMR and TRLMR groups, respectively). The metabolism in the different groups was analyzed by ultra‐performance liquid chromatography coupled with quadrupole‐orbitrap mass spectrometry (UPLC/Q‐Orbitrap MS).ResultsThe results showed that the concentration of glimepiride increased in RLM and TRLM after treatment with ginsenoside Rg3. Five metabolites (M1–M5) of glimepiride were found, and they were named 3N‐hydroxyglimepiride, hydroxyglimepiride, 1,2‐epoxy ether‐3‐hydroxyglimepiride, 1N‐hydroxyglimepiride and 1N,2C,S,O,O‐epoxy ether‐3‐hydroxyglimepiride. The metabolite of ginsenoside Rg3 was ginsenoside Rh2.ConclusionsAn in vitro incubation system with RLM and TRLM was developed. The system revealed pathways that produce glimepiride metabolites. Ginsenoside Rg3 may inhibit the activity of cytochrome P450 enzymes in vitro. The present study showed that ginsenoside Rg3 and glimepiride may be combined for the treatment of T2DM.

Gamma-ray attenuation competences and optical characterization of MgO–MoO3–TeO2–BaO glasses

The kinetic, optical features, and gamma-ray shielding competence of 0.8 [xBaO (1 − x)MgO]·0.2MoO3·2TeO2:x = 0,0.3, 0.5, 0.7, and 1 mol% named as M1–M5 have been investigated. The highest value of the optical electronegativity (χ*) was achieved for the M4 glass sample, while the lowest was achieved for the M5 sample. The nonlinear refractive index $$\left( {n_{2}^{{{\text{optical}}}} } \right)$$ and nonlinear optical susceptibility (χ3) followed the same trend. The values of the bulk modulus (KB−C) decreased from 144.52 GPa for the M1 glass to 79.14 GPa for the M5 glass with increasing the BaO content. The longitudinal modulus (LB−C) decreased from 289.61 to 158.58 GPa and the Young’s modulus (EB−C) decreased from 261.74 to 143.17 GPa for M1–M5 glasses. Poisson’s ratio (σB−C) for all glasses (M1–M5) has a constant value (0.198) as the average cross-link density ( $$\overline{n}_{{\text{c}}}$$ ) for all glasses is constant. The transmission factor (TF) of M1–M5 glasses decreases significantly as the mol% of BaO increases. The half value thickness (HVT) follows the trend of (M1)HVT > (M2)HVT > (M3)HVT > (M4)HVT > (M5)HVT. The effective atomic number (Zeff) follows the trend of (M1)Zeff < (M2)Zeff < (M3)Zeff < (M4)Zeff < (M5)Zeff. This observation comes from the fact that BaO has a greater atomic number than MgO, so that as the concentration of BaO increases in the glasses, the Zeff of the glasses increases as well. Generally, since a lower TF means a greater attenuating ability, it can be determined that the M5 glass has the better shielding ability and that the greater BaO content leads to greater attenuation in the investigated glass system.

Three Dimensional Weightbearing CT Assessment of Metatarsal Osteotomies for Hallux Valgus Correction

Category:Bunion; Midfoot/ForefootIntroduction/Purpose:Hallux valgus (HV) is a tri-plane deformity of the foot corresponding to a medial deviation of the first metatarsal and a lateral deviation of the hallux. Understanding key angles between bones, as well as how these deformity changes in each plane, is critical to generating pre-operative insights into the most effective surgical correction of the deformity. While two- dimenional (2D) imaging can provide some information; utilizing three-dimensional (3D) imaging can include more precise and accurate measures of hallux valgus. The purpose of this study is to evaluate the metatarsal osteotomies for correction of hallux valgus deformity in axial, coronal and sagittal plane with 2D and 3D measurements with the hypothesis that 3D measurements will provide greater accuracy of pre and post surgical changesMethods:Ten cadaveric specimens were selected and weight-bearing CT scans were taken pre operatively with an applied an axial load of 80 pounds. Midshaft osteotomies were then performed on the cadaveric specimens followed by weight-bearing CT scans taken post-operatively.3D models of the pre-operative and post-operative specimens were created and differences in pre and post operative changes were analyzed using conventional 2D and 3D models of the first metatarsal (M1), second metatarsal (M2), fifth metatarsal (M5), and proximal phalanx of the hallux (PP1) using a paired student t-test. Quantitative examination of foot and ankle offset (FAO) alignment along with congruity of first metatarsal phalangeal and first tarsometatarsal jointsResults:3D measurements of the Inter-Metatarsal (IM) Angle, was 12.3 degrees pre-opeative and 10.4 degrees post-operative with no significant differences in all three planes while the M1M5 Angle, measured between the principle axes of the first metatarsal and fifth metatarsal was 25.3 degrees pre-operative and 22.0 degrees post-operative were statistically significant with the greatest change in the axial plane. 2D measurements of the hallux valgus angle, measured the longitudineal axes of the first metatarsal and proximal phalange of the hallux was 22.6 degrees pre opereative and 21.7 degrees post opereative with no statistical difference while the metatarsal parabola, measured in two dimensions projected onto the axial plane was 157.1 degrees before and 141.5 degrees after surgery was statistical significant.Conclusion:When comparing 2D and 3D pre and post surgical hallux valgus values, the only significant differences were identified in the absolute M1M5 values in the axial plane and a significant change was also observed in the metatarsal parabola angle. While the metatarsal parabola angle are sensitive measures, these results suggest that the M1 M5 angle allows for precise, efficient measurements in axial, coronal and sagittal planes that is previously unknown through two-dimensional radiographic measurements for quantifying the effect of metatarsal osteotomies on hallux valgus

In Vitro Metabolism of DWP16001, a Novel Sodium-Glucose Cotransporter 2 Inhibitor, in Human and Animal Hepatocytes.

DWP16001 is currently in a phase 2 clinical trial as a novel anti-diabetes drug for the treatment of type 2 diabetes by selective inhibition of sodium-glucose cotransporter 2. This in vitro study was performed to compare the metabolism of DWP16001 in human, dog, monkey, mouse, and rat hepatocytes, and the drug-metabolizing enzymes responsible for the metabolism of DWP16001 were characterized using recombinant human cytochrome 450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes expressed from cDNAs. The hepatic extraction ratio of DWP16001 in five species ranged from 0.15 to 0.56, suggesting that DWP16001 may be subject to species-dependent and weak-to-moderate hepatic metabolism. Five phase I metabolites (M1–M5) produced by oxidation as well as three DWP16001 glucuronides (U1–U3) and two hydroxy-DWP16001 (M1) glucuronides (U4, U5), were identified from hepatocytes incubated with DWP16001 by liquid chromatography-high resolution mass spectrometry. In human hepatocytes, M1, M2, M3, U1, and U2 were identified. Formation of M1 and M2 from DWP16001 was catalyzed by CYP3A4 and CYP2C19. M3 was produced by hydroxylation of M1, while M4 was produced by hydroxylation of M2; both hydroxylation reactions were catalyzed by CYP3A4. The formation of U1 was catalyzed by UGT2B7, but UGT1A4, UGT1A9, and UGT2B7 contributed to the formation of U2. In conclusion, DWP16001 is a substrate for CYP3A4, CYP2C19, UGT1A4, UGT1A9, and UGT2B7 enzymes. Overall, DWP16001 is weakly metabolized in human hepatocytes, but there is a potential for the pharmacokinetic modulation and drug–drug interactions, involved in the responsible metabolizing enzymes of DWP16001 in humans.

The M1 muscarinic acetylcholine receptor in the crypt stem cell compartment mediates intestinal mucosal growth.

Localization of a specific subtype of the muscarinic acetylcholine receptor in the crypt stem cell compartment suggests a critical role in intestinal mucosal homeostasis. Here we demonstrate the localization of the M1 muscarinic acetylcholine receptor to the stem cell compartment and demonstrate increase morphometric and proliferative parameters when this is stimulated in vivo. These data provide novel information about this complex signaling microenvironment and offer potential future therapeutic targets for future study.