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Background: Preeclampsia is a pregnancy syndrome that may utilize multiple pathogenic mechanisms. Insufficient trophoblast invasion and impaired uterine spiral artery remodeling are believed to be the pathological basis; yet the underlying mechanisms remain largely unclear. Methods: The placental BCAM (basal cell adhesion molecule) expression and important clinical indicators were detected and correlation analysis was performed. MiRNAs directly targeting BCAM were predicted and further verified by dual-luciferase reporter gene, and the downstream molecular mechanisms of BCAM were investigated in both HTR-8/SVneo and JAR cells. In addition, pregnant/nonpregnant rats were treated with adenoviruses containing BCAM shRNA genes (Ad-shBCAM) on gestational 9.5 days to detect the preeclamptic features. Results: The BCAM is highly expressed on the trophoblast membrane and decreased in the preeclamptic placentae. In HTR-8/SVneo and JAR cells, BCAM knockdown inhibited trophoblast proliferation, migration, and invasion, and suppressed phosphorylation on Y705 of STAT3 dependent on the downregulation of PIK3R6. Moreover, miR-199a-5p mediated the degradation of BCAM and also inhibited trophoblast proliferation, migration, and invasion. In vivo, BCAM deficiency induced a preeclampsia-like phenotype included elevated systolic blood pressure, proteinuria, impaired morphology and function of multiple organs (placenta, liver, and kidney), and fetal growth restriction. The expression of placenta BCAM/PIK3R6/p-STAT3 signaling was also downregulated in this preeclampsia rat model. Conclusions: MiR-199a-5p mediated–BCAM deficiency contributes to the suppression of trophoblast proliferation, migration, and invasion by inhibiting PIK3R6/p-STAT3 signaling, which may lead to poor placentation and result in preeclampsia-like phenotypes. Our study provides a new academic perspective on the pathogenesis of preeclampsia.

The East Kunlun orogenic belt (EKOB) is located in the northeastern part of the Qinghai-Tibetan Plateau, China. Voluminous Silurian-Devonian granitoids were formed during the Proto-Tethys Ocean subduction and collision process. In this study, zircon U-Pb age dating, in-situ Hf isotope analyses, and whole rock major and trace element analyses have been carried out on granitoids from the central to eastern EKOB. The formation ages of granodiorite in the Bairiqili area, the granodiorite in the Wulonggou area are 410 ± 2 Ma and 396 ± 1 Ma, respectively, and the granodiorites show I-type features. The Wulonggou syenogranite with a formation age of 398 ± 2 Ma has a high differentiation index (D.I. = 89.59–92.43), and may belong to the high fractionated I-type granite. The Lalangmai tonalite with a formation age of 423 ± 2 Ma has high Sr (339–590 µg/g), eHf(t) (1.5–7.3), and low Y (3.45–6.33 µg/g), which are similar to modern adakites. The Lalangmai tonalite is the latest adakite record during the Proto-Tethys evolution in EKOB. Combined with previous studies, it is concluded that the granitoids from Cambrian to Devonian divided into four episodes. The first episode (515–436 Ma) mainly consists of I-type island arc granites and adakite, which are formed in a subduction environment. The second episode (436–427 Ma) is characterized by the S-type granites related to the collision. The third episode (427–420 Ma) is the transition period between the collision and the post-collision environment. In the fourth episodes (420–385 Ma), granitoids were formed in post-collision extensional environment, which is characterized by I-type and A-type granites. The upwelling of asthenosphere material is likely caused by the collapse of the orogenic belt. After 420 Ma, I-type and A-type granites formed at different depths but in the same environment.

In pharmaceutical industry, a deep understanding on the physical properties of drug substance and excipients is critical for the quality control of solid dose drug product. The purpose of this work is to develop a quantitative simulation calibration and prediction platform to model powder compression by applying the Discrete Element Method (DEM). The Luding elasto-plastic contact model was applied for particle-particle interactions. The loading stiffness, the unloading stiffness ratio, and the particle density (which served by adjusting the bulk volume of a specific mass of particles) were determined as influential parameters in this study. Calibration was established between DEM parameters and compression profile of pharmaceutical powders in a short timeframe. This platform could capture the main compressibility characteristics of pharmaceutical materials and could successfully provide quantitative predictions on compression profiles of mixtures. It was recommended for development of solid dose DP especially when the amount of DS was limited.

Fluidized bed dryer often used in the pharmaceutical industry for drying of wet granules. Coupled computational fluid dynamics (CFD) - discrete element method (DEM) is frequently used to model the drying process because of its ability to obtain the relevant information at the particle level. However, it becomes almost impossible to model the industrial scale fluidized bed dryer using the coupled CFD-DEM method because of the presence of large number of particles [Formula: see text]. To reduce the number of particles to be tracked in the simulation, coarse grained coupled CFD-DEM method was developed by researchers where a certain number of particles of the original system was represented by a relatively bigger particle in the coarse-grained system. The appropriate scaling of the particle-particle and particle-fluid interaction forces is necessary to make sure that the dynamics of the coarse-grained particles/parcels accurately represent the dynamics of the original particles. The coarse-graining of the drying process of pharmaceutical granules during fluidization needs systematic coarse-graining of the momentum, heat, and solvent vapor transfer process. A coarse grained coupled CFD-DEM method was used to model the momentum and heat transfer during the fluidization of pharmaceutical granules. It was shown that the heat transfer during the fluidization of large number of particles could be predicted by simulating a smaller number of bigger particles with appropriate scaling of particle-particle heat and momentum transfer, and particle-fluid heat and momentum transfer at significantly smaller computational time. This model can be further extended by including a coarse-grained moisture transport model in future.

Modifying surfaces using free radical polymerization (FRP) offers a means to incorporate the diverse physicochemical properties of vinyl polymers onto new materials. Here, we harness the universal surface attachment of polydopamine (PDA) to "prime" a range of different surfaces for free radical polymer attachment, including glass, cotton, paper, sponge, and stainless steel. We show that the intrinsic free radical species present in PDA can serve as an anchor point for subsequent attachment of propagating vinyl polymer macroradicals through radical-radical coupling. Leveraging a straightforward, twofold soak-wash protocol, FRP over the PDA-functionalized surfaces results in covalent polymer attachment on both porous and nonporous substrates, imparting new properties to the functionalized materials, including enhanced hydrophobicity, fluorescence, or temperature responsiveness. Our strategy is then extended to covalently incorporate PDA nanoparticles into organo-/hydrogels via radical cross-linking, yielding tunable PDA-polymer composite networks. The propensity of PDA free radicals to quench FRP is studied using in situ

Converging lines of evidence suggest an association between schizophrenia and prenatal neurodevelopmental disorders. Preeclampsia is a multisystem disease based on the coexistence of pregnancy and elevated blood pressure, which increases the risk for offspring abnormal neurodevelopment. Previous studies have showed maternal preeclampsia is associated with an increased risk of offspring schizophrenia, but the molecular mechanism remains unclear. In this study, we sought to identify key protein-coding genes between maternal preeclampsia and offspring schizophrenia. GSE53987 and GSE166846 datasets from Gene Expression Omnibus (GEO) database were analysed to obtain common differentially expressed genes (DEGs) between preeclampsia and schizophrenia. GSE62105 dataset was analysed to identify the DEGs' expressions in neural cells from one control and one schizophrenic patient. GSE92845 dataset was analysed to describe the changes of the DEGs in human neural stem cells. In total, we obtained ten common DEGs. All of them expressed differently in neural cells of the control and schizophrenic patient. We chose the six DEGs that had similar trend in both neural cells and UCB from preeclampsia patients and analysed their expressions in human neural stem cells over time. We found the expressions of CKAP5 and SAT1 in day 30 had significant difference comparing with those in day 0. The KEGG pathway analysis of their interaction proteins showed they were involved with metabolism. Our results may provide a new insight for genetic basis of relationship between maternal preeclampsia and offspring schizophrenia.

Drying of wet granules in a fluidized bed dryer is an important part of the pharmaceutical tablet manufacturing process. Complicated gas-solid flow patterns appear in the fluidized bed dryer, and interphase momentum, heat, and mass transfer happen during the drying process. A coupled computational fluid dynamics (CFD)-discrete element method (DEM)-based approach was used to model the drying process of pharmaceutical wet granules in a fluidized bed dryer. The evaporation of water from the surfaces of the particles and the cohesion force between the particles due to the formation of liquid bridges between the particles were also considered in this model. The model was validated by comparing the model predictions with the experimental data available from the literatures. The validated model was used to investigate the drying kinetics of the wet granules in the fluidized bed dryer. The results from numerical simulations showed that the dynamics and rate of increase of temperature of wet particles were considerably different from those of dry particles. Finally, the model was used to investigate the effects of inlet air velocity and inlet air temperature on the drying process. The model predicted increase in drying rate with the increase of inlet air velocity and inlet air temperature. This model can help not only to understand the multiphase multicomponent flow in fluidized bed dryer but also to optimize the drying process in the fluidized bed dryer.

Purpose. Osteoporosis is a complication of type 2 diabetes, and it is characterized by reduced bone mass, augmented bone fragility, and increased risk of fracture, thus reducing patient quality of life, especially in the elderly. Ferroptosis has been implicated in the pathological process of type 2 diabetic osteoporosis (T2DOP), but the specific underlying mechanisms remain largely unknown. This study clarified the role of activating transcription factor 3 (ATF3) in T2DOP and explored its specific regulatory mechanism, providing a new treatment target for T2DOP. Methods. We cultured hFob1.19 cells in high glucose (HG, 35 mM) and knocked down ATF3 using short hairpin RNA (shRNA). We then measured cell viability, assessed morphology, quantified the expression of ATF3 and glutathione peroxidase 4 (GPX4), detected the levels of reactive oxygen species (ROS) and lipid peroxides, and determined the osteogenic function of osteoblasts. Cystine/glutamate antiporter (system Xc-) activity was evaluated by determining the expression of SLC7A11 and the levels of glutathione (GSH) and extracellular glutamate. We constructed a T2DOP rat model and observed the effect of ATF3 on ferroptosis and T2DOP by knocking down ATF3 using small interfering RNA (siRNA). Then, we evaluated the levels of iron metabolism, lipid peroxidation, and bone turnover in serum, detected the expression of ATF3, SLC7A11, and GPX4 in bone tissues, and assessed bone microstructure using microcomputed tomography. Results. ATF3 expression was increased in osteoblasts under HG condition and in T2DOP rats. Inhibiting the function of ATF3 increased GPX4 levels and reduced the accumulation of ROS and lipid peroxides. These changes inhibited the ferroptosis of osteoblasts and improved osteogenic function. In addition, HG induced ATF3 upregulation, resulting in decreased SLC7A11 expression and lower levels of intracellular GSH and extracellular glutamate. Conclusion. Osteoblast ferroptosis under HG conditions is induced by ATF3-mediated inhibition of system Xc- activity, and these events contribute to T2DOP pathogenesis.

China is the first country in the world to grow, make and taste tea, and has a colorful tea culture. After absorbing some of the connotations of Chinese tea culture, the United Kingdom, through innovation and integration, has condensed a unique British tea culture. The two countries that both have tea have very different tea situations. This paper focuses on comparing the differences between the two countries at the level of the material culture in tea culture and exploring the reasons behind the differences.

This paper describes a zero-dimensional model for evaluating the mass flow rate history of a solid rocket motor igniter. Based on the results of an igniter-firing experiment, in which the igniter is the only source of combustion gas and no propellant is ignited, the proposed model can be used to compute the mass flow rate of the igniter. Different species and temperature-dependent properties, such as the specific heat for each species, are considered. The coupling between the flow field variables in the combustion chamber and the heat transfer at the gas-solid interface is computed in a segment way. Calculations are performed for different species and properties, and the errors are discussed. Using the computed igniter mass flow rate as a boundary condition, a two-dimensional calculation is performed for validation purposes. The results are in good agreement with experimental data. The proposed model can be used to provide reasonable boundary conditions for solid rocket motor simulations and to evaluate the performance of igniters. Although derived on the basis of a small-scale solid rocket motor, the model has the potential to be used in large-scale systems.

Background: The efficacy and safety of anti–nerve growth factor (NGF) antibody therapy used for osteoarthritis (OA) pain are controversial. Purpose: To evaluate the efficacy and safety of anti-NGF antibody therapy via a meta-analysis of randomized controlled trials (RCTs). Study Design: Systematic review; Level of evidence, 1. Methods: PubMed, the Cochrane Central Register of Controlled Trials, Embase, and the Web of Science databases were searched for RCTs assessing anti-NGF antibody treatments for hip and knee OA. A total of 623 records were retrieved from the databases. A random-effects model was used to assess primary and secondary outcomes. Bias was assessed using the Cochrane Collaboration tool, funnel plots, and the Egger test. Subgroup analyses were used to assess the efficacy and safety of the independent variables. Sensitivity analysis was conducted to evaluate the effectiveness of tanezumab and the effectiveness of anti-NGF antibodies compared to active comparator drugs. We present the effects of dose, administration mode, and treatment duration on the efficacy and safety of anti-NGF antibody therapy. Results: There were 19 RCTs included in our meta-analysis. Anti-NGF antibody treatment showed significant improvements on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain, physical function, and stiffness as well as on a patient global assessment (PGA). The overall standardized mean differences were as follows: WOMAC pain (–0.31 [95% CI, –0.36 to –0.26]; Z = 11.75; P 2 = 38%), WOMAC physical function (−0.36 [95% CI, –0.41 to –0.30]; Z = 12.67; P < .001; I 2 = 44%), WOMAC stiffness (–3.59 [95% CI, –4.87 to –2.30]; Z = 5.47; P < .001; I 2 = 98%), and PGA (−0.28 [95% CI, –0.34 to –0.22]; Z = 9.39; P < .001; I 2 = 50%). Anti-NGF antibody treatment resulted in a greater incidence of adverse events (risk ratio, 1.09 [95% CI, 1.06 to 1.12]; Z = 5.60; P < .001; I 2 = 0%). The incidence of serious adverse events was similar between the treatment and control groups (risk ratio, 1.15 [95% CI, 0.98 to 1.34]; Z = 1.71; P = .09; I 2 = 0%). Conclusion: Anti-NGF antibody treatment significantly relieved pain and improved function in patients with hip and knee OA. However, no conclusion could be drawn regarding the optimal treatment plan for anti-NGF antibodies when all 3 variables (dose, administration mode, and treatment duration) were combined in the analyses.

Current techniques for the generation of cell-laden microgels are limited by numerous challenges, including poorly uncontrolled batch-to-batch variations, processes that are both labor- and time-consuming, the high expense of devices and reagents, and low production rates; this hampers the translation of laboratory findings to clinical applications. To address these challenges, we develop a droplet-based microfluidic strategy based on metastable droplet-templating and microchannel integration for the substantial large-scale production of single cell-laden alginate microgels. Specifically, we present a continuous processing method for microgel generation by introducing amphiphilic perfluoronated alcohols to obtain metastable emulsion droplets as sacrificial templates. In addition, to adapt to the metastable emulsion system, integrated microfluidic chips containing 80 drop-maker units are designed and optimized based on the computational fluid dynamics simulation. This strategy allows single cell encapsulation in microgels at a maximum production rate of 10 ml h−1 of cell suspension while retaining cell viability and functionality. These results represent a significant advance toward using cell-laden microgels for clinical-relevant applications, including cell therapy, tissue regeneration and 3D bioprinting.

Background: There is increasing and inconsistent evidence of a relationship between hypertensive disorders of pregnancy (HDP) and season of delivery or conception.Methods: Four databases, the Cochrane Library, PubMed, EMBASE and Web of Science, were searched until September 29th, 2021. Two authors extracted data independently. A random effects model and the Mantel-Haenszel method were used to calculate pooled ORs and 95% CIs.Results: Twenty articles were included in the systematic review, and 11 articles were included in the meta-analysis. The quantitative analysis of the association between delivery season and HDP showed that the odds of HDP was higher in women who deliver in winter than in those who delivered in summer (OR=1.18, 95% CI 1.02-1.38, p < 0.001) and all other seasons (OR = 1.17, 95% CI 1.03-1.34, p

Purpose Amyand’s hernia is a rare hernia defined as an inguinal hernia that contains the appendix within the hernia sac. Current treatment of Amyand’s hernia remains controversial. Our study retrospectively reviewed 6 cases of Amyand’s hernia, aiming to provide a reference for the surgical treatment of Amyand's hernia. Methods Six patients diagnosed with Amyand’s hernia from September 2010 to May 2020 were retrospectively enrolled in our study. We summarized clinical data of six patients including the chief complaint, physical examinations, laboratory examinations, imaging examinations, surgical methods, and postoperative treatments and outcomes. Results The diagnosis of six cases with Amyand’s hernia was made during surgery. Two patients had normal appendixes whereas the remaining four patients had appendicitis. Two patients with normal appendix received tension-free mesh repair through the inguinal incision. Among those with inflamed or perforated appendixes, two received mesh repair and the other two did not. The discharge time after surgery of six patients was 9.8 ± 6.1 days. One patient suffered from a wound infection. No additional postoperative complications were detected. Conclusions Computed tomography and ultrasonography are helpful but limited in the definite diagnosis of Amyand’s hernia. The presence of a normal appendix does not require to be resected, but appendicectomy is necessary if the appendix is inflamed. The treatment of Amyand's hernia should be tailored based on the patient's condition and the type of Amyand's hernia.

Given that the modification of stem cell-derived extracellular vesicles (EVs) can enhance their regenerative efficiency, an increasing number of studies pay attention to the therapeutic potential of hypoxic preconditioning of stem cell-derived EVs (Hypo-EVs) in cardiac repair. Our meta-analysis aims to evaluate the cardiac repair of Hypo-EVs in preclinical animal models of myocardial infarction (MI). We searched PubMed, EMBASE, and the Web of Science up to January 2021. The primary outcome was left ventricular ejection fraction (LVEF). The second outcomes were left ventricular fractional shortening (LVFS) and infarct size. Random-effects modeling was used to calculate pooled weighted mean differences (WMDs) and 95% confidence intervals (CIs). Nine studies satisfied the inclusion criteria. Compared with the model group, pooled analyses demonstrated that stem cell-derived EVs culturing in normal oxygen environment (Nor-EVs) can improve LVEF (WMD: 9.07, 95% CI: 6.76 to 11.38

It has become acentral question to guarantee the security of sensitive data in enterprise information systems. Actually, different enterprises may grasp asymmetric information due to their scales. ...

Purpose: Amyand’s hernia is a rare hernia defined as an inguinal hernia that contains the appendix within the hernia sac. Current treatment of Amyand’s hernia remains controversial. Our study retrospectively reviewed 6 cases of Amyand’s hernia, aiming to provide a reference for the surgical treatment of Amyand's hernia.Methods: Six patients diagnosed with Amyand’s hernia from September 2010 to May 2020 were retrospectively enrolled in our study. We summarized clinical data of six patients including the chief complaint, physical examinations, laboratory examinations, imaging examinations, surgical methods, and postoperative treatments and outcomes.Results: The diagnosis of six cases with Amyand’s hernia was made during surgery. Two patients had normal appendixes whereas the remaining four patients had inflamed appendixes. Two patients with normal appendix received tension-free mesh repair through the inguinal incision. Among those with inflamed or perforated appendixes, two received mesh repair and the other two did not. The discharge time after surgery of six patients was 9.8±6.1 days. One patient suffered from an incision infection. No additional postoperative complications were detected. Conclusions: Computed tomography and ultrasonography are helpful but limited in the definite diagnosis of Amyand’s hernia. The presence of a normal appendix does not require to be resected, but appendicectomy is necessary if the appendix is inflamed. The treatment of Amyand's hernia should be tailored based on the patient's condition and the type of Amyand's hernia.

Crowd counting, which has been widely adopted for estimating the number of people in safety-critical scenes, is shown to be vulnerable to adversarial examples in the physical world (e.g., adversarial patches). Though harmful, adversarial examples are also valuable for evaluating and better understanding model robustness. However, existing adversarial example generation methods for crowd counting lack strong transferability among different black-box models, which limits their practicability for real-world systems. Motivated by the fact that attacking transferability is positively correlated to the model-invariant characteristics, this paper proposes the Perceptual Adversarial Patch (PAP) generation framework to tailor the adversarial perturbations for crowd counting scenes using the model-shared perceptual features. Specifically, we handcraft an adaptive crowd density weighting approach to capture the invariant scale perception features across various models and utilize the density guided attention to capture the model-shared position perception. Both of them are demonstrated to improve the attacking transferability of our adversarial patches. Extensive experiments show that our PAP could achieve state-of-the-art attacking performance in both the digital and physical world, and outperform previous proposals by large margins (at most +685.7 MAE and +699.5 MSE). Besides, we empirically demonstrate that adversarial training with our PAP can benefit the performance of vanilla models in alleviating several practical challenges in crowd counting scenarios, including generalization across datasets (up to -376.0 MAE and -354.9 MSE) and robustness towards complex backgrounds (up to -10.3 MAE and -16.4 MSE).

Background COVID-19 has become a global pandemic. Its occurrence has substantially affected the psychological condition of pregnant women. The purpose of this study is to learn about the incidence of anxiety and depression among pregnant women during the pandemic, and to conduct a meta-analysis of the existing research.Methods PubMed, Web of Science and EMBASE were searched without a lower time limit and up to August 13, 2020. The incidences of anxiety and depression among pregnant women were synthesized and discussed.Results The prevalence of anxiety in 8 studies with a total sample size of 7493 individuals was 43% (95% confidence interval: 0.28-0.58), and the prevalence of depression in 7 studies with a sample size of 6116 people was 32% (95% confidence interval: 0.26-0.37). Significant heterogeneity was detected across studies of these incidence estimates. Subgroup analysis included the economic status to explore the sources of heterogeneity, and Egger’s test was conducted to examine the publication bias.Conclusions Since significant heterogeneity has been detected in studies of anxiety and depression, we must interpret the results with caution. As the COVID-19 pandemic will not end in a short time, corresponding psychological interventions must be implemented to address the mental health of pregnant women.