Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. Alveolar epithelial cells (AECs) primarily sense ...alveolar hypoxia, but the role of AECs in HPH remains unclear. In this study, we explored whether AECs are involved in pulmonary vascular remodeling and constriction.
In the constructed rat HPH model, hemodynamic and morphological characteristics were measured. By treating AECs with hypoxia, we further detected the levels of superoxide dismutase 2 (SOD2), catalase (CAT), reactive oxygen species (ROS) and hydrogen peroxide (H
O
), respectively. To detect the effects of AECs on pulmonary vascular remodeling and constriction, AECs and pulmonary artery smooth cells (PASMCs) were co-cultured under hypoxia, and PASMCs and isolated pulmonary artery (PA) were treated with AECs hypoxic culture medium. In addition, to explore the mechanism of AECs on pulmonary vascular remodeling and constriction, ROS inhibitor N-acetylcysteine (NAC) was used.
Hypoxia caused pulmonary vascular remodeling and increased pulmonary artery pressure, but had little effect on non-pulmonary vessels in vivo. Meanwhile, in vitro, hypoxia promoted the imbalance of SOD2 and CAT in AECs, leading to increased ROS and hydrogen peroxide (H
O
) production in the AECs culture medium. In addition, AECs caused the proliferation of co-cultured PASMCs under hypoxia, and the hypoxic culture medium of AECs enhanced the constriction of isolated PA. However, treatment with ROS inhibitor NAC effectively alleviated the above effects.
The findings of present study demonstrated that AECs were involved in pulmonary vascular remodeling and constriction under hypoxia by paracrine H
O
into the pulmonary vascular microenvironment.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
► The thickness of AZ31B magnesium alloy sheet after V-bending increases. ► The neutral layer shifts to the tension zone of the sheets. ► The deformation mechanism between outer and inner region is ...asymmetric. ► The shift of neutral layer has an effect on the springback.
The evolution of springback and neutral layer for AZ31B magnesium alloy sheet was investigated by V-bending tests at temperatures from 50 to 300°C. Moreover, in order to perceive the influence of the punch radii on springback and offset of neutral layer, the tests with punch radii at 7.5, 8.1, 8.7 and 9.3mm were conducted at 100°C. The results show that the neutral layer shifts to the tension zone of the sheets. The coefficient of neutral layer (k-value) decreases with the increase of temperature and punch radii. This is mainly because of the asymmetry between the outer tension layer and inner compression layer during bending. The outer tension region is dominated by slip, while the inner compression region is dominated by twinning. With the increase of temperature, the asymmetry of tension–compression becomes weaker, and the offset of neutral layer decreases. The offset of neutral layer increases as punch radii decreases. The shift of neutral layer of AZ31B sheet results in the calculation of springback bigger than the reality.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The present study was conducted to determine whether and how store-operated Ca
2+
entry (SOCE) in glomerular mesangial cells (MCs) was altered by high glucose (HG) and diabetes. Human MCs were ...treated with either normal glucose or HG for different time periods. Cyclopiazonic acid-induced SOCE was significantly greater in the MCs with 7-day HG treatment and the response was completely abolished by GSK-7975A, a selective inhibitor of store-operated Ca
2+
channels. Similarly, the inositol 1,4,5-trisphosphate-induced store-operated Ca
2+
currents were significantly enhanced in the MCs treated with HG for 7 days, and the enhanced response was abolished by both GSK-7975A and La
3+
. In contrast, receptor-operated Ca
2+
entry in MCs was significantly reduced by HG treatment. Western blotting showed that HG increased the expression levels of STIM1 and Orai1 in cultured MCs. A significant HG effect occurred at a concentration as low as 10 mM, but required a minimum of 7 days. The HG effect in cultured MCs was recapitulated in renal glomeruli/cortex of both type I and II diabetic rats. Furthermore, quantitative real-time RT-PCR revealed that a 6-day HG treatment significantly increased the mRNA expression level of STIM1. However, the expressions of STIM2 and Orai1 transcripts were not affected by HG. Taken together, these results suggest that HG/diabetes enhanced SOCE in MCs by increasing STIM1/Orai1 protein expressions. HG upregulates STIM1 by promoting its transcription but increases Orai1 protein through a posttranscriptional mechanism.
In this paper, the Lie group method is performed on a special dark fluid, the Chaplygin gas, which describes both dark matter and dark energy in the present universe. Based on an optimal system of ...one-dimensional subalgebras, similarity reductions and group invariant solutions are given. Finally, by means of Ibragimov’s method, conservation laws are obtained.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Stem-cell-based therapy is very promising for Alzheimer's disease (AD), yet has not become a reality. A critical challenge is the transplantation microenvironment, which impacts the therapeutic ...effect of stem cells. In AD brains, amyloid-beta (Aβ) peptides and inflammatory cytokines continuously poison the tissue microenvironment, leading to low survival of grafted cells and restricted efficacy. It is necessary to create a growth-supporting microenvironment for transplanted cells. Recent advances in AD studies suggest that the asparaginyl endopeptidase (AEP) is a potential intervention target for modifying pathological changes. We here chose APP/PS1 mice as an AD model and employed pharmacological inhibition of the AEP for one month to improve the brain microenvironment. Thereafter, we transplanted neural stem cells (NSCs) into the hippocampus and maintained therapy for one more month. We found that inhibition of AEPs resulted in a significant decrease of Aβ, TNF-α, IL-6 and IL-1β in their brains. In AD mice receiving NSC transplantation alone, the survival of NSCs was at a low level, while in combination with AEP inhibition pre-treatment the survival rate of engrafted cells was doubled. Within the 2-month treatment period, implantation of NSCs plus pre-inhibition of the AEP significantly enhanced neural plasticity of the hippocampus and rescued cognitive impairment. Neither NSC transplantation alone nor AEP inhibition alone achieved significant efficacy. In conclusion, pharmacological inhibition of the AEP ameliorated brain microenvironment of AD mice, and thus improved the survival and therapeutic efficacy of transplanted stem cells.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Glaciers are attracting increasing attention in the context of climate change, and glacier tourism has also become a popular tourist product. However, few studies have been conducted concerning the ...image of glacier tourism destinations. To address this gap in the literature, in this study, we extracted destination images from 138,709 visitor reviews of 107 glacier tourism destinations on TripAdvisor using latent Dirichlet allocation (LDA) topic modeling, identified destination image characteristics using salience−valence analysis (SVA), and analyzed the differences in glacier tourism destination image characteristics across seasons and regions. According to the findings, the image of a glacier tourism destination consists of 14 dimensions and 53 attributes, with landscapes and specific activities representing the core image and viewing location and necessity representing the unique image. We identified significant seasonal and regional differences in the image of glacier tourism destinations. Finally, we discussed the unique image of glacier tourism destinations, the reasons for differences in the images, and the characteristics of different glacier tourism regions. This research could assist in the scientific management of their core images by glacier tourism destinations, as well as in the rational selection of destinations and travel timing by glacier tourists.
The occurrence of segmental/lobar pattern pneumonia (S/L-PP) in children has recently increased. The pathogens of the disease may change for the misuse of antibiotics and the application of vaccines. ...Therefore, pathogens positive in hospitalized children with S/L-PP and their association with clinical characteristics may have changed. The aim of this study was to analyze the pathogens positive in hospitalized children with S/L-PP and their association with clinical characteristics.
The current study analyzed the epidemiological and clinical characteristics of pathogens positive in children with S/L-PP under 14 years old at a single hospital between 1st Jan 2014 and 31st Dec 2018 retrospectively. The pathogens were detected by microbial cultivation, indirect immunofluorescence of the kit (PNEUMOSLIDE IgM), Elisa, and/or real-time PCR in the samples of the patients.
A total of 593 children with S/L-PP received treatment at a single hospital during the study period by inclusion criteria. Four hundred fifty-one patients were single positive for one pathogen and 83 patients were positive for at least 2 pathogens. Mycoplasma pneumoniae (M.pneumoniae) (72.34%) was the most commonly detected pathogen, followed by Streptococcus pneumoniae (S.pneumoniae) (8.77%). The prevalence of M.pneumoniae in children with S/L-PP increased with time (p < 0.05). The positive rate of M.pneumoniae increased with ages of patients (p < 0.05). M.pneumoniae was statistically associated with the extrapulmonary manifestations while S.pneumoniae was statistically associated with abnormal white blood cells (WBCs) and C reactive proteins (CRPs) (p < 0.05).
M.pneumoniae was the most positive pathogen in children with S/L-PP. The positive rate of M.pneumoniae in children with S/L-PP increased with time and the ages of children. M.pneumoniae was associated with extrapulmonary manifestations while S.pneumoniae was associated with abnormal WBCs and CRPs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Shell cross-linked nanoparticles were fabricated by the complexation of poly(3-methacrylamido phenylboronic acid) (PMAPBA) and thiolated chitosan (chitosan-SH) via boronic acid-related reactions. The ...formation of PMAPBA/chitosan-SH nanoparticles was confirmed by transmission electron microscopy, dynamic light scattering, and UV spectroscopy. The nanoparticles had a narrow size distribution with a relatively high positive charge density, and the size and zeta potential of the nanoparticles correlated with the chitosan-SH concentration. Furthermore, owing to the cross-linking of the nanoparticle shell, insulin was encapsulated in the nanoparticles with a loading capacity of up to 18%. The release of insulin from the nanoparticles slowed down because of the presence of disulfide bonds and increased with increasing glucose level in the medium. The structure of the released insulin was not distorted. More importantly, the nanoparticles had good cytocompatibility, as demonstrated by in vitro experiments. The simplicity of this strategy along with a high loading capacity, glucose sensitivity, and cytocompatibility of the produced nanoparticles should significantly boost their application in self-regulated insulin delivery.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To evaluate the interaction of depression and anxiety with the development of recurrent pregnancy loss (RPL).
A nested case-control study involving 2558 participants was conducted with data from the ...prospective Miscarriage Woman Cohort study between 2017 and 2019 in the province of Gansu, China. The questionnaire data, self-rating anxiety scale and self-rating depression scale were collected after each participant's first miscarriage. Information on RPL outcomes was obtained from the medical records within the subsequent 2 years. All patients diagosed RPL were recruited as cases whilst a randomly selected group of women with only one miscarriage in the past were recruited as controls. The logistic regression and the interaction effects between anxiety and depression and RPL were analysed.
The prevalence of anxiety (n = 325, 28.7% vs. n = 278, 19.5%) and depression symptoms (n = 550, 48.6% vs. n = 589, 41.3%) for the 1132 RPL cases were higher than 1426 non-RPL controls (P < 0.001). After adjusting for possible confounding variables, the odds ratio (OR) value, reflecting the multiplicative interaction, was 1.91 (95% CI 1.50-2.44, P < 0.001) for cases with both anxiety and depression symptoms compared with the non-RPL group. The relative excess risk of interaction value, reflecting the additive interaction between anxiety and depression to RPL was 1.15 (95% CI 0.32-4.21). Moreover, the adjusted OR for RPL cases with mild anxiety and severe depression was 2.77 (95% CI 1.07-44.14, P < 0.001), for RPL cases with severe anxiety and mild depression was 4.23 (95% CI 1.01-22.21, P < 0.001), for RPL cases with severe anxiety and moderate depression was 4.34 (95% CI 1.03-21.28, P < 0.001) and for RPL cases with severe anxiety and severe depression was 5.95 (95% CI 1.09-45.09, P < 0.05).
Either depression or anxiety alone could increase the risk of subsequent RPL. Anxiety and depression had a synergistic effect after the first miscarriage which increased the development of subsequent RPL disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background The Oxford classification of immunoglobulin A (IgA) nephropathy (IgAN) provides a histopathologic grading system that is associated with kidney disease outcomes independent of clinical ...features. We evaluated the Oxford IgAN classification in a large cohort of patients from China. Study Design Retrospective study. Setting & Participants 1,026 adults with IgAN from 18 referral centers in China. Inclusion criteria and statistical analysis were similar to the Oxford study. Predictors Histologic findings of mesangial hypercellularity score, endocapillary proliferation, segmental sclerosis or adhesion, crescents, necrosis, and tubular atrophy/interstitial fibrosis. Clinical features, blood pressure, estimated glomerular filtration rate (eGFR), proteinuria, and treatment modalities. Outcomes Time to a 50% reduction in eGFR or end-stage renal disease (the combined event); the rate of eGFR decline (slope of eGFR); proteinuria during follow-up. Results Compared with the Oxford cohort, the Chinese cohort had a lower proportion of patients with mesangial hypercellularity (43%) and endocapillary proliferation (11%), higher proportion with segmental sclerosis or adhesion (83%) and necrosis (15%), and similar proportion with crescents (48%) and tubular atrophy/interstitial fibrosis (moderate, 24%; severe, 3.3%). During a median follow-up of 53 (25th-75th percentile, 36-67) months, 159 (15.5%) patients reached the combined event. Our study showed that patients with a mesangial hypercellularity score higher than 0.5 were associated with a 2.0-fold (95% CI, 1.5-2.8; P <0.001) higher risk of the combined event than patients with a score of 0.5 or lower. Patients with tubular atrophy/interstitial fibrosis of 25%-50% and >50% versus <25% were associated with a 3.7-fold (95% CI, 2.6-5.1; P <0.001) and 15.1-fold (95% CI, 9.5-24.2; P <0.001) higher risk of the combined event, respectively. Endocapillary proliferation, glomerular crescents, and necrosis were not significant. Limitations Retrospective study; the therapeutic interventions were miscellaneous. Conclusions We confirmed the associations of mesangial hypercellularity and tubular atrophy/interstitial fibrosis with kidney disease outcomes.
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