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Endometrial injury is an important cause of intrauterine adhesion (IUA), amenorrhea and infertility in women, with limited effective therapies. Recently, stem cells have been used in animal experiments to repair and improve injured endometrium. To date, our understanding of adipose-derived stem cells (ADSCs) in endometrial injury repair and their further therapeutic mechanisms is incomplete. Here, we examined the benefit of ADSCs in restoration of injured endometrium by applying a rat endometrial injury model. The results revealed by immunofluorescence showed that green fluorescent protein (GFP)-labelled ADSCs can differentiate into endometrial epithelial cells in vivo. At 30 days after ADSCs transplantation, injured endometrium was significantly improved, with increased microvessel density, endometrial thickness and glands when compared with the model group. Furthermore, the fertility of rats with injured endometrium in ADSCs group was improved and had a higher conception rate (60% vs 20%, P = 0.014) compared with the control phosphate-buffered saline (PBS) group. However, there was no difference in the control group compared with the sham group. In addition, expression levels of the oestrogen receptor Eα/β (ERα, ERβ) and progesterone receptor (PR) detected by western blot and enzyme-linked immunosorbent assay (ELISA) were higher in the ADSCs group than in the PBS group. Taken together, these results suggested that ADSC transplantation could improve endometrial injury as a novel therapy for IUA.
Multidimensional instabilities always develop with time during the process of radiation pressure acceleration, and are detrimental to the generation of monoenergetic proton beams. In this paper, a sharp-front laser is proposed to irradiate a triple-layer target (the proton layer is set between two carbon ion layers) and studied in theory and simulations. It is found that the thin proton layer can be accelerated once to hundreds of MeV with monoenergetic spectra only during the hole-boring (HB) stage. The carbon ions move behind the proton layer in the light-sail (LS) stage, which can shield any further interaction between the rear part of the laser and the proton layer. In this way, proton beam instabilities can be reduced to a certain extent during the entire acceleration process. It is hoped such a mechanism can provide a feasible way to improve the beam quality for proton therapy and other applications.
The effect of maternal folate intake on small-for-gestational-age (SGA) births remains inconclusive. The present study aimed to investigate the associations of maternal folate intake from diet and supplements with the risk of SGA births using data from a cross-sectional study in Shaanxi Province of Northwest China. A total of 7307 women who were within 12 months (median 3; 10th–90th percentile 0–7) after delivery were included. Two-level models were adopted to examine the associations of folate (dietary folate, supplemental folic acid and total folate) intake with the risk of SGA births and birth weight Z score, controlling for a minimum set of confounders that were identified in a directed acyclic graph. Results showed that a higher supplemental folic acid intake during the first trimester was negatively associated with the risk of SGA births (≤60 d v. non-use: OR 0·80; 95 % CI 0·66, 0·96; >60 d v. non-use: OR 0·78; 95 % CI 0·65, 0·94; Ptrend = 0·010; per 10-d increase: OR 0·97; 95 % CI 0·95, 0·99). A higher total folate intake during pregnancy was associated with a reduced risk of SGA births (highest tertile v. lowest tertile: OR 0·77; 95 % CI 0·64, 0·94; Ptrend = 0·010; per one-unit increase in the log-transformed value: OR 0·81; 95 % CI 0·69, 0·95). A similar pattern was observed for the birth weight Z score. Our study suggested that folic acid supplementation during the first trimester and a higher total folate intake during pregnancy were associated with a reduced risk of SGA births.
The mean skin-friction drag in a wall-bounded turbulent flow can be decomposed into different physics-informed contributions based on the mean and statistical turbulence quantities across the wall layer. Following Renard & Deck’s study (J. Fluid Mech., vol. 790, 2016, pp. 339–367) on the skin-friction drag decomposition of incompressible wall-bounded turbulence, we extend their method to a compressible form and use it to investigate the effect of density and viscosity variations on skin-friction drag generation, using direct numerical simulation data of compressible turbulent channel flows. We use this novel decomposition to study the skin-friction contributions associated with the molecular viscous dissipation and the turbulent kinetic energy production and we investigate their dependence on Reynolds and Mach number. We show that, upon application of the compressibility transformation of Trettel & Larsson (Phys. Fluids, vol. 28, 2016, 026102), the skin-friction drag contributions can be only partially transformed into the equivalent incompressible ones, as additional terms appear representing deviations from the incompressible counterpart. Nevertheless, these additional contributions are found to be negligible at sufficiently large equivalent Reynolds number and low Mach number. Moreover, we derive an exact relationship between the wall heat flux coefficient and the skin-friction drag coefficient, which allows us to relate the wall heat flux to the skin-friction generation process.
The determination of low boron concentrations in silicate glasses by electron probe microanalysis (EPMA) remains a significant challenge. The internal interferences from the diffraction crystal, i.e. the Mo-B4C large d-spacing layered synthetic microstructure crystal, can be thoroughly diminished by using an optimized differential mode of pulse height analysis (PHA). Although potential high-order spectral interferences from Ca, Fe, and Mn on the BKα peak can be significantly reduced by using an optimized differential mode of PHA, a quantitative calibration of the interferences is required to obtain accurate boron concentrations in silicate glasses that contain these elements. Furthermore, the first-order spectral interference from ClL-lines is so strong that they hinder reliable EPMA of boron concentrations in Cl-bearing silicate glasses. Our tests also indicate that, due to the strongly curved background shape on the high-energy side of BKα, an exponential regression is better than linear regression for estimating the on-peak background intensity based on measured off-peak background intensities. We propose that an optimal analytical setting for low boron concentrations in silicate glasses (≥0.2 wt% B2O3) would best involve a proper boron-rich glass standard, a low accelerating voltage, a high beam current, a large beam size, and a differential mode of PHA.
We report on an initial long-term study of dissolved inorganic and organic carbon (DIC) from Sabino Creek, located in Sabino Canyon, Pima County, Arizona. The purpose of this study was to monitor changes in dissolved radiocarbon (14C) with time and to understand the processes contributing to these variations. Our results span the period 2009–2016 and show a mixing trend between dissolved inorganic and organic carbon modern end-members with an older component. This study provides preliminary information for more detailed research on recycling of organic components in this stream system.
Annexin A2 (ANXA2) is reported to be associated with cancer development. To investigate the roles ANXA2 plays during the development of cancer, the RNAi method was used to inhibit the ANXA2 expression in caco2 (human colorectal cancer cell line) and SMMC7721 (human hepatocarcinoma cell line) cells. The results showed that when the expression of ANXA2 was efficiently inhibited, the growth and motility of both cell lines were significantly decreased, and the development of the motility relevant microstructures, such as pseudopodia, filopodia, and the polymerization of microfilaments and microtubules were obviously inhibited. The cancer cell apoptosis was enhanced without obvious significance. The possible regulating pathway in the process was also predicted and discussed. Our results suggested that ANXA2 plays important roles in maintaining the malignancy of colorectal and hepatic cancer by enhancing the cell proliferation, motility, and development of the motility associated microstructures of cancer cells based on a possible complicated signal pathway.
Major depressive disorder (MDD) is highly heterogeneous and can be classified as treatment-resistant depression (TRD) or antidepressant-responsive depression (non-TRD) based on patients' responses to antidepressant treatment. Methods for distinguishing between TRD and non-TRD are critical clinical concerns. Deficits of cortical inhibition (CI) have been reported to play an influential role in the pathophysiology of MDD. Whether TRD patients' CI is more impaired than that of non-TRD patients remains unclear.
Paired-pulse transcranial magnetic stimulation (ppTMS) was used to measure cortical inhibitory function including GABAA- and GABAB-receptor-related CI and cortical excitatory function including glutamate-receptor-related intracortical facilitation (ICF). We recruited 36 healthy controls (HC) and 36 patients with MDD (non-TRD, n = 16; TRD, n = 20). All participants received evaluations for depression severity and ppTMS examinations. Non-TRD patients received an additional ppTMS examination after 3 months of treatment with the SSRI escitalopram.
Patients with TRD exhibited reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI), as shown by abnormally higher estimates, than those with non-TRD or HC (F = 11.030, p < 0.001; F = 10.309, p < 0.001, respectively). After an adequate trial of escitalopram treatment, the LICI of non-TRD reduced significantly (t = − 3.628, p < 0.001), whereas the ICF remained lower than that of HC and showed no difference from pretreatment non-TRD.
TRD was characterized by relatively reduced CI, including both GABAA- and GABAB-receptor-mediated neurons while non-TRD preserved partial CI. In non-TRD, SSRIs may mainly modulate GABAB-receptor-related LICI. Our findings revealed distinguishable features of CI in antidepressant-resistant and responsive major depression.
Firms that are located in a cluster may confront cooperation and competition at the same time. The advantage of cooperation and the disadvantage of competition on a firm may need to examine the firm survival in a cluster as the cluster evolves. Employing the population ecology viewpoint, this study tries to address coopetition issues in a cluster to examine the impact of coopetition on firm survival rate. Analyzing yacht industry data in Taiwan from 1957–2010, this study indicates that the founding rate of yacht firms will be positively related with the cluster size. Additionally, during the competition period, those firms located inside the cluster may have a higher dissolution rate than those firms outside the cluster, indicating the disadvantage of competition on the firm. Finally, this study finds that those firms located inside the cluster will be more likely to become larger and have capabilities to survive. The results in this study provide insights on addressing coopetition issues in a cluster.
Bidimensional empirical mode decomposition (BEMD) is used to identify attached eddies in turbulent channel flows and quantify their relationship with the mean skin-friction drag generation. BEMD is an adaptive, non-intrusive, data-driven method for mode decomposition of multiscale signals especially suitable for non-stationary and nonlinear processes such as those encountered in turbulent flows. In the present study, we decompose the velocity fluctuations obtained by direct numerical simulation of channel flows into BEMD modes characterized by specific length scales. Unlike previous works (e.g. Flores & Jiménez, Phys. Fluids, vol. 22(7), 2010, 071704; Hwang, J. Fluid Mech., vol. 767, 2015, pp. 254–289), the current approach employs naturally evolving wall-bounded turbulence without modifications of the Navier–Stokes equations to maintain the inherent turbulent dynamics, and minimize artificial numerical enforcement or truncation. We show that modes identified by BEMD exhibit a self-similar behaviour, and that single attached eddies are mainly composed of streaky structures carrying intense streamwise velocity fluctuations and vortex packets permeating in all velocity components. Our findings are consistent with the existence of attached eddies in actual wall-bounded flows, and show that BEMD modes are tenable candidates to represent Townsend attached eddies. Finally, we evaluate the turbulent-drag generation from the perspective of attached eddies with the aid of the Fukagata–Iwamoto–Kasagi identity (Fukagata et al., Phys. Fluids, vol. 14(11), 2002, pp. L73–L76) by splitting the Reynolds shear stress into four different terms related to the length scale of the attached eddies.
The antibacterial hydrogels can be widely used in the biomedical area owing to their excellent properties. The main limitation of antibacterial hydrogels is their poor mechanical strength. In this study, the novel hydrogels were fabricated with a mixture of silk fibroin (SF), chitosan (CH), agarose (AG), and silver nanoparticles (SNPs) via facile reaction condition without inorganic substances. The mechanical property of these fabricated hydrogels can be modulated by the concentration of SF or AG. The rheological studies demonstrated enhanced elasticity of CH-doped hydrogels. Because of the presence of CH and Ag in hydrogels, the antimicrobial property against gram-positive and gram-negative bacteria was exhibited. Cytocompatibility test proved the very low toxic nature of the hydrogels. In addition, these composite hydrogels have a smaller porosity, higher swelling ratio, and good compatibility, indicating their great potential for biomedical application.
Maternal one-carbon metabolism during pregnancy is crucial for fetal development and programming by DNA methylation. However, evidence on one-carbon biomarkers other than folate is lacking. We, therefore, investigated whether maternal plasma methyl donors, that is, choline, betaine and methionine, are associated with birth outcomes. Blood samples were obtained from 115 women during gestation (median 26·3 weeks, 90 % range 22·7–33·0 weeks). Plasma choline, betaine, methionine and dimethylglycine were measured using HPLC-tandem MS. Multivariate linear and logistic regression models were used to estimate the association between plasma biomarkers and birth weight, birth length, the risk of small-for-gestational-age and large-for-gestational-age (LGA). Higher level of maternal betaine was associated with lower birth weight (–130·3 (95 % CI –244·8, –15·9) per 1 sd increment for log-transformed betaine). Higher maternal methionine was associated with lower risk of LGA, and adjusted OR, with 95 % CI for 1 sd increase in methionine concentration was 0·44 (95 % CI 0·21, 0·89). Stratified analyses according to infant sex or maternal plasma homocysteine status showed that reduction in birth weight in relation to maternal betaine was only limited to male infants or to who had higher maternal homocysteine status (≥5·1 µmol/l). Higher maternal betaine status was associated with reduced birth weight. Maternal methionine was inversely associated with LGA risk. These findings are needed to be replicated in future larger studies.
We use the Carleson measure-embedding theorem for weighted Bergman spaces to characterize the positive Borel measures
on the unit disc such that certain analytic function spaces of Dirichlet type are embedded (compactly embedded) in certain tent spaces associated with a measure
. We apply these results to study Volterra operators and multipliers acting on the mentioned spaces of Dirichlet type.
Previous studies in schizophrenia revealed abnormalities in the cortico-cerebellar-thalamo-cortical circuit (CCTCC) pathway, suggesting the necessity for defining thalamic subdivisions in understanding alterations of brain connectivity.
To parcellate the thalamus into several subdivisions using a data-driven method, and to evaluate the role of each subdivision in the alterations of CCTCC functional connectivity in patients with schizophrenia.
There were 54 patients with schizophrenia and 42 healthy controls included in this study. First, the thalamic structural and functional connections computed, based on diffusion magnetic resonance imaging (MRI, white matter tractography) and resting-state functional MRI, were clustered to parcellate thalamus. Next, functional connectivity of each thalamus subdivision was investigated, and the alterations in thalamic functional connectivity for patients with schizophrenia were inspected.
Based on the data-driven parcellation method, six thalamic subdivisions were defined. Loss of connectivity was observed between several thalamic subdivisions (superior-anterior, ventromedial and dorsolateral part of the thalamus) and the sensorimotor system, anterior cingulate cortex and cerebellum in patients with schizophrenia. A gradual pattern of dysconnectivity was observed across the thalamic subdivisions. Additionally, the altered connectivity negatively correlated with symptom scores and duration of illness in individuals with schizophrenia.
The findings of the study revealed a wide range of thalamic functional dysconnectivity in the CCTCC pathway, increasing our understanding of the relationship between the CCTCC pathway and symptoms associated with schizophrenia, and further indicating a potential alteration pattern in the thalamic nuclei in people with schizophrenia.
G-protein-coupled receptor 142 (GPR142) belongs to rhodopsin family. GPR142 and GPR119, both Gq-coupled receptors, are expressed in pancreatic β cells of pancreas; their activation eventually leads to triggering of insulin secretion. In this paper, through a systems and synthetic biology approach, the effect of a common hit compound has been investigated in GPR142 and GPR119 pathways. This hit that has the potential to be developed as a lead for nanodrug was obtained through high-throughput virtual screening. The hit compound was further docked with nanoparticles (GOLD, SPION, and CeO2). The probable effect of this potential hit on insulin secretion in type 2 diabetes and its dynamic behavior was explored. Kinetic simulation was performed for cross-validation of its role in both the pathways. This study opens up a probable avenue in therapy of type 2 diabetes through regulation of GPR142 and GPR119 receptors. The biological circuit constructed may further have an application as a modulator to control the up- and downregulation of the biochemical pathway and can be implemented as sensors or nanochips for therapy.