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Abstract This article investigates the evolution of vortex structures in the impeller channel of a multiphase pump. By capturing the vortices in the impeller channel using the vorticity and Q‐criterion, the generation location of the vortex structures is analyzed, and the pressure fluctuations induced by vortices in the main flow passage of the impeller are studied in terms of their time‐ and frequency‐domain characteristics. The relationship between the vorticity and the amplitude of pressure fluctuations at the main frequency of the impeller is further investigated. This study develops a method of identifying vortices in the impeller channel of the multiphase pump, and reveals the intrinsic connection between the vortices and pressure fluctuations in the main flow passage. These findings offer some suggestions for eliminating the influence of vortices and enhancing the pressurizing capabilities of multiphase pumps.

Abstract The paper combines experimental and numerical simulation methods to investigate the tip leakage vortex (TLV) in an oil–gas multiphase pump. The study aims to understand the evolution and dynamic characteristics of the TLV. The vorticity decomposition theory is used to analyze the spatial–temporal evolution, transient behavior, and rigid vorticity of the TLV. The findings reveal that the TLV is formed near the pressure surface when the tip clearance jet passes through the shear layer. In one impeller rotation period, transient fluctuations of the TLV are attributed to pressure differences and velocity changes across the tip clearance, and the TLV undergoes two split–dissipation–recurrence processes within one impeller rotation cycle. The presence of the gas phase enhances the scale and strength of the TLV while prolonging its existence in the flow channel. Analysis based on the rigid vorticity transport equation shows that the growth of the TLV and collapse are primarily governed by the rigid vortex generation term. The Coriolis force term contributes to stabilizing the TLV, while the rigid vorticity stretching term affects its shape. Furthermore, the gas phase significantly increases the value of the Rigid vorticity Curl of pseudo‐Lamb vector Term (RCT), which plays a crucial role in the prolonged existence of the TLV under gas–liquid two‐phase conditions. From an inlet gas void fraction of 0%–20%, the RCT value increases by 4.8 × 106/s2, the entropy production value increases by 75.55%, and the hydraulic efficiency decreases by 16.29%.

Association standardization of oil and gas pipeline network in China has been in progress for quite a period. However, it is urgent to further accelerate its standardized and high-quality development facing the new requirements, such as high-quality development of the industry, autonomy enhancement, extensive international oil and gas cooperation, etc. In attempt to assist achieving the goal, this research analyzed the data pertaining to association standards for oil and gas pipeline network published in China, focusing on its quantitative change, subject content, field distribution, and drafting units, and employed a complex network algorithm to illustrate the present state of association standardization efforts with a diagram. Based on the aforementioned work, this research found out that there are three main operational modes for association standards organizations, that is professional organizations in this field being totally committed, organizations in relevant field being largely involved and others participating occasionally. The analysis results demonstrate that many problems exist in current association standardization work of oil and gas pipeline network, such as lacking of energy and systematic planning, insufficient in the number of standards, especially of high-quality standards, and the implementation of supervision by industry authorities. The research, in dealing with these problems, promoted several countermeasures, including(1) to establish a correct recognition of the importance of association standardization;(2) to build a national organization to promote coordinated development;(3) leveraging the role of Pipe China to promote openness and integration;(4) to develop a multi-level working mechanism to improve the overall quality; and(5) to refine the responsibilities of the supervising authorities to facilitate high-quality development, etc.

In this paper, a gas microbody is proposed to address the issues related to the limited load-carrying capacity of squeezed film gas bearings, complex mechanical structures, large overall dimensions, high manufacturing costs, and complicated installation. Initially, the gas continuity equation of squeezed film was established for modal analysis, without regard to the gas inertial force and the gas volume force which are all far less than the gas viscous force. Then the load-carrying characteristics of squeezed film gas bearing were studied and analyzed with the fluid-structure coupling method. The load-carrying capacity of the squeezed film gas bearing is determined by factors such as bearing amplitude, rotor-axial clearance, and rotor-axial tile contact area. In conclusion, the load-carrying capacity can be enhanced by increasing the amplitude value, reducing the clearance, and increasing the contact area. Among them, when adjusting the amplitude and clearance to improve the bearing’s load-carrying capacity, the stability of bearing operation should be considered. When the clearance is too small, the pressure distribution of the air film will be uneven, and when the contact area is too large, the development of the air film in all directions will be asymmetrical.

Much research has been conducted to improve the defect-detection rate and detection accuracy of the imaging technology used in terahertz nondestructive testing. Due to the power limit of light sources and noise interference in terahertz equipment, images have low resolution and fuzzy defect edges. Hence, improving the resolution is crucial for detecting defects. We designed an edge detection network structure based on a traditional deep neural network. Besides, we devised a node-fusing strategy to train the network. It demonstrates significant improvement of the resolution of the terahertz defect contour. A quartz fiber composites with embedded defects was tested with our network. The results showed that the proposed super-resolution reconstruction algorithm improves resolution, particularly on the edges of defect contours.

In order to improve the submerged cutting performance of water abrasive suspension jet an experimental investigation on the two-phase flow structure of submerged water jet with semi-coaxial air ventilation is conducted by the method of high-speed camera observation under the condition of flow dynamic similarity, and its unsteady behavior under different conditions is evaluated by analyzing of sequence images. Experiment results show that the flow pattern of air-ventilated jet depends upon the ventilation flow rate. It may be classified into bubbly flow surrounded jet, continuous air-layer covered jet and cavity-bubble flow surrounded jet. In the case of non-ventilation, high-speed water jet into water is accompanied by intensive cavitation and the flow field appears to be a narrow jet surrounded by cavitation bubble clouds. By ventilating to the cavitating jet, air-bubbles become bigger gradually and a cavity area is formed at the exit of nozzle head. When the ventilation flow ratio reaches to the level of 5 a large cavity covering the jet is formed and a continuous air-layer covered jet is then generated. Image analysis demonstrates that the continuous air-layer covering the liquid jet pulsates and sheds downstream periodically. The Strouhal number defined by the dominant frequency of jet pulsation decreases quickly with the increase of ventilation flow rate in the range of Cq ≤ 5. At a suitable ventilation flow ratio (Cq ≈ 6 ~ 8) a relative long stable continuous air-layer covering the jet is generated at high time ratio, which will dramatically enhance the processing ability of submerged water jets. Cutting tests demonstrates that the cutting ability of air ventilated jet depends on the ventilation flow ratio. The relation of processing ability with the flow structure of air ventilated jet is clarified.

The high‐order chromatin structure, together with DNA methylation and other epigenetic marks, plays a vital role in gene regulation and displays abnormal status in cancer cells. Theoretical analyses are expected to provide a more unified understanding of the multi‐omics data on the large variety of samples, and hopefully a common picture of carcinogenesis. In particular, we are interested in the question of whether an underlying origin DNA sequence exists for these epigenetic alterations. The human genome consists of two types of megabase‐sized domain based on the distribution of CpG islands (CGIs) that show distinct structural, epigenetic, and transcriptional properties: CGI‐rich and CGI‐poor domains. Through an integrated analysis of chromatin structure, DNA methylation, and RNA sequencing data, we found that, in carcinogenesis, the two different types of domain display different structural changes and have an increased number of DNA methylation differences and transcriptional‐level differences, compared with in noncancer cells. We also compared the structural features among carcinogenesis, senescence, and mitosis, showing the possible connection between chromatin structure and cell state, which could affect vital cancer‐related properties. In summary, chromatin structure, DNA methylation, and gene expression, as well as their changes observed in several types of cancers, show a dependence on multiscale DNA sequence heterogeneity.

Abstract A recent genome-wide copy number variations (CNVs) scan identified a 16q12.2 deletion that included the carboxylesterase 1 (CES1) gene, which is important in the metabolism of fatty acids and cholesterol. We aimed to investigate whether CES1 CNVs was associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in a Chinese Han population. A case–control study was conducted among 303 patients diagnosed with NAFLD and 303 age (± 5) and sex-matched controls from the Affiliated Nanping First Hospital of Fujian Medical University in China. The copy numbers of CES1 were measured using TaqMan quantitative real-time polymerase chain reaction (qPCR) and serum CES1 was measured using enzyme-linked immunosorbent assays. The Chi-squared test and a logistic regression model were used to evaluate the association between CES1 CNVs and NAFLD susceptibility. The distribution of CES1 CNVs showed a higher frequency of CNVs loss ( 2) was not. There was a suggestion of an association between increased CES1 serum protein levels and CNVs losses among cases, although this was not statistically significant (P = 0.07). Copy number losses (

Abstract Background The prevalence of Non-alcoholic fatty liver disease (NAFLD) is increasing and emerging as a global health burden. In addition to environmental factors, numerous studies have shown that genetic factors play an important role in the development of NAFLD. Copy number variation (CNV) as a genetic variation plays an important role in the evaluation of disease susceptibility and genetic differences. The aim of the present study was to assess the contribution of CNV to the evaluation of NAFLD in a Chinese population. Methods Genome-wide analysis of CNV was performed using high-density comparative genomic hybridisation microarrays (ACGH). To validate the CNV regions, TaqMan real-time quantitative PCR (qPCR) was utilized. Results A total of 441 CNVs were identified, including 381 autosomal CNVs and 60 sex chromosome CNVs. By merging overlapping CNVs, a genomic CNV map of NAFLD patients was constructed. A total of 338 autosomal CNVRs were identified, including 275 CNVRs with consistent trends (197 losses and 78 gains) and 63 CNVRs with inconsistent trends. The length of the 338 CNVRs ranged from 5.7 kb to 2.23 Mb, with an average size of 117.44 kb. These CNVRs spanned 39.70 Mb of the genome and accounted for ~ 1.32% of the genome sequence. Through Gene Ontology and genetic pathway analysis, we found evidence that CNVs involving nine genes may be associated with the pathogenesis of NAFLD progression. One of the genes (NLRP4 gene) was selected and verified by quantitative PCR (qPCR) method with large sample size. We found the copy number deletion of NLRP4 was related to the risk of NAFLD. Conclusions This study indicate the copy number variation is associated with NAFLD. The copy number deletion of NLRP4 was related to the risk of NAFLD. These results could prove valuable for predicting patients at risk of developing NAFLD.

BackgroundAbdominal obesity and adipocytokines are closely related to atherosclerosis, and adiponectin level is considered one of the important clinical indicators. This study aimed to analyze the associations of abdominal visceral fat content and adiponectin level with intracranial atherosclerotic stenosis (ICAS).MethodsA total of 186 patients were enrolled in this study. Patients were distributed into ICAS and non-ICAS by the degree of artery stenosis. Plasma adiponectin levels and the ratio of visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT) were measured. The related factors of intracranial atherosclerotic stenosis were determined using multivariable logistic regression analysis.ResultsThe VAT/SAT ratio (OR, 26.08; 95% CI, 5.92–114.83; p < 0.001) and adiponectin (OR, 0.61; 95% CI, 0.44–0.84; p = 0.002) were found to be the independent predictors of ICAS in a multivariable logistic regression analysis. The prevalence of ICAS increased (T1: 27.4%; T2: 50.0%; T3: 75.8%) as the VAT/SAT ratio tertile increased (p < 0.001). The prevalence of ICAS decreased (T1: 72.6%; T2: 54.8%; T3: 25.8%) as the adiponectin tertile increased (p < 0.001). In ROC curves analysis, VAT/SAT ratio had a sensible accuracy for the prediction of ICAS. The optimal cut-off value of VAT/SAT ratio to predict ICAS in this study was 1.04 (AUC: 0.747; p < 0.001; sensitivity: 67.4%; specificity: 74.7%). The optimal adiponectin cutoff was 3.03 ug/ml (AUC: 0.716; p < 0.001; sensitivity:75.8%; specificity: 61.5%).ConclusionHigher VAT/SAT ratio and lower plasma adiponectin levels were closely related to the increased risk of intracranial atherosclerotic stenosis.

BackgroundCOVID-19 (coronavirus disease 2019) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seriously endangers people's lives. The variation in SARS-CoV-2 makes the research and development of vaccines and specific drugs particularly important. However, the prevention and diagnosis of COVID-19 cannot be underestimated in the control of the epidemic.Case PresentationWe introduced a 65-year-old female patient who was diagnosed with COVID-19. The SARS-CoV-2 nucleic acid test result of this patient was positive again during treatment. It took 85 days from the first symptom to the final cure. According to the known reports, she is currently the patient with the longest virus shedding in Sichuan Province, China. Due to the patient's special condition, she was treated in four hospitals before and after, and she was diagnosed with type 2 diabetes mellitus (T2DM) and right lung metastatic adenocarcinoma. We fully introduced the patient's epidemiological history, diagnosis, testing, and treatment process. The patient was finally discharged from the hospital under the treatment of antiviral, hypoglycaemic, anti-anxiety, and a combination of Chinese and Western medicine.ConclusionsThe epidemic is still rampant, and we should not relax our efforts in the prevention and control of viruses. For the elderly, especially those who are suffering from complications or vulnerable to diseases, it is recommended to extend the observation time. Additionally, medical workers should pay attention to the mental state of patients.

Background: Ginsenoside Rb1, a triterpene saponin, is derived from the Panax ginseng root and has potent antiinflammatory activity. In this study, we determined if Rb1 can increase macrophage phagocytosis and elucidated the underlying mechanisms. Methods: To measure macrophage phagocytosis, mouse peritoneal macrophages or RAW 264.7 cells were cultured with fluorescein isothiocyanate–conjugated Escherichia coli, and the phagocytic index was determined by flow cytometry. Western blot analyses were performed. Results: Ginsenoside Rb1 increased macrophage phagocytosis and phosphorylation of p38 mitogen-activated protein kinase (MAPK), but inhibition of p38 MAPK activity with SB203580 decreased the phagocytic ability of macrophages. Rb1 also increased Akt phosphorylation, which was suppressed by LY294002, a phosphoinositide 3-kinase inhibitor. Rb1-induced Akt phosphorylation was inhibited by SB203580, (5Z)-7-oxozeaenol, and small-interfering RNA (siRNA)–mediated knockdown of p38α MAPK in macrophages. However, Rb1-induced p38 MAPK phosphorylation was not blocked by LY294002 or siRNA-mediated knockdown of Akt. The inhibition of Akt activation with siRNA or LY294002 also inhibited the Rb1-induced increase in phagocytosis. Rb1 increased macrophage phagocytosis of IgG-opsonized beads but not unopsonized beads. The phosphorylation of p21 activated kinase 1/2 and actin polymerization induced by IgG-opsonized beads and Rb1 were inhibited by SB203580 and LY294002. Intraperitoneal injection of Rb1 increased phosphorylation of p38 MAPK and Akt and the phagocytosis of bacteria in bronchoalveolar cells. Conclusion: These results suggest that ginsenoside Rb1 enhances the phagocytic capacity of macrophages for bacteria via activation of the p38/Akt pathway. Rb1 may be a useful pharmacological adjuvant for the treatment of bacterial infections in clinically relevant conditions. Keywords: Akt, Ginsenoside Rb1, Macrophage, p38, Phagocytosis

We design optimization on the overall blade structure of a vortex pump conducted by using the orthogonal test method to clarify the matching relationship of impeller and casing structures and then improve the hydraulic performance of the vortex pump. Based on two different impeller structures of forward-deflecting (denoted as R1 − F2) and backward-deflecting (denoted as F1 − R2), key parameters describing the impeller structure are calculated through optimization for the objective function of hydraulic efficiency by means of orthogonal tests and computational fluid dynamic simulations. Optimization computations show that the forward-deflecting blade impeller is superior to the backward-deflecting one. Model test of the optimized vortex pump is carried out calculating the error from the comparison of pump efficiencies calculated by model test and numerical simulation is calculated to be less than 6%. The experimental verification shows that the flow simulation has some errors. The weight of structure parameters such as the blade installation angle (α), the blade deflecting angle (β), the position of blade deflecting point (L), the radius (r) of smoothing arc at the deflecting point, the wedge type (W) of blade, to the lift head, the flow rate, and the efficiency of the pump is investigated, through multiparameter optimizations. Visualization observation of flows in the model pump consisted of a back-placed impeller and a front vaneless chamber is further performed. The characteristic of vortex formation predicted by flow simulation agrees with the result of visualization observation. The above results demonstrate that the optimum impeller type of vortex pump is forward-deflecting blade impeller. The optimum combination of the key structure parameters is that the deflection angle of the blade inlet (α) equals 30°, the position of blade deflecting point lM = 2/3 L, the chamfering radius (r) at the deflecting point r = 3 mm, and the best wedge type is axial deflecting blade.

With the increase of power level and integration in electric vehicle controllers, the heat flux of the key silicon-based IGBT (Insulated Gate Bipolar Transistor) device has reached its physical limit. At present, third-generation semiconductor devices including SiC MOSFETs (Metal-Oxide-Semiconductor Field-Effect Transistor) are gradually replacing the dominant IGBT module. The hybrid IGBT module consists of both and can improve the performance and reduce the cost of controllers. Limits due to the installation space, location, and other conditions in the car make it difficult to meet the requirements of controllers with an air-cooled heatsink due to their large size and limited heat dissipation capacity. A smaller and more powerful water-cooled heatsink case is required to ensure the heat dissipation of the IGBT in the controller. Based on previous experience in finite element numerical simulation, hydrodynamics calculation, and heat transfer calculation, ANSYS Workbench finite element software was used to analyze the thermal resistance of each structure inside the module and the heatsink structure. The fluid characteristics and heat transfer performance of three different flow channel structures were analyzed, and the design of the cooling flow fin was improved to provide a reference for the heat dissipation of the hybrid IGBT module.

Cognitive deficits are long-lasting consequences of drug use, yet the convergent mechanism by which classes of drugs with different pharmacological properties cause similar deficits is unclear. We find that both phencyclidine and methamphetamine, despite differing in their targets in the brain, cause the same glutamatergic neurons in the medial prefrontal cortex of male mice to gain a GABAergic phenotype and decrease expression of their glutamatergic phenotype. Suppressing drug-induced gain of GABA with RNA-interference prevents appearance of memory deficits. Stimulation of dopaminergic neurons in the ventral tegmental area is necessary and sufficient to produce this gain of GABA. Drug-induced prefrontal hyperactivity drives this change in transmitter identity. Returning prefrontal activity to baseline, chemogenetically or with clozapine, reverses the change in transmitter phenotype and rescues the associated memory deficits. This work reveals a shared and reversible mechanism that regulates the appearance of cognitive deficits upon exposure to different drugs.

Autism spectrum disorders (ASD) can be caused by environmental factors. These factors act early in the development of the nervous system and induce stereotyped repetitive behaviors and diminished social interactions, among other outcomes. Little is known about how these behaviors are produced. In pregnant women, delivery of valproic acid (VPA) (to control seizure activity or stabilize mood) or immune activation by a virus increases the incidence of ASD in offspring. We found that either VPA or Poly Inosine:Cytosine (which mimics a viral infection), administered at mouse embryonic day 12.5, induced a neurotransmitter switch from GABA to glutamate in PV- and CCK-expressing interneurons in the medial prefrontal cortex by postnatal day 10. The switch was present for only a brief period during early postnatal development, observed in male and female mice at postnatal day 21 and reversed in both males and females by postnatal day 30. At postnatal day 90, male mice exhibited stereotyped repetitive behaviors and diminished social interaction while female mice exhibited only stereotyped repetitive behavior. Transfecting GAD1 in PV- and CCK-expressing interneurons at postnatal day 10, to reintroduce GABA expression, overrode the switch and prevented expression of autistic-like behavior. These findings point to an important role of neurotransmitter switching in mediating the environmental causes of autism.

Vortex pumps have good non-clogging performance owing to their impellers being retracted into retraction cavities, but they are much less efficient than ordinary centrifugal pumps. In this paper, numerical simulations were performed on a model of the 150WX200-20 vortex pump for four different blade types, and the influence of blade structure on pump performance was determined. The simulations revealed the existence of axial vortices in the flow passage between the blades in the impeller region. The geometric characteristics of these axial vortices were more regular in two-phase solid-liquid flow than single-phase liquid flow. The presence of the solid phase reduced the vortex strength compared with the single-phase flow and suppressed the increase in size of the secondary circulation vortex. It was found, however, that the blade shape had a greater influence on the circulating flow than the presence of the solid phase. The flow state of the medium flowing out of the impeller domain had a direct effect on the circulating flow with this effect being related to the law governing the flow of the medium in the flow channel between the blades. It was found that the performance of a front-bent blade was the best and that of a curved blade the worst. This influence of blade type on the internal flow structure was used to further explain the relationship between the internal flow structure and the external characteristics of the vortex pump, the understanding of which is crucial for blade selection and hydraulic optimization.

By studying the substrate material, structure, chip distribution, and array form of the multi-chip light-emitting diode (LED) package, the heat-dissipation capacity of the LED package is improved. Finite element analysis and steady-state thermal analysis are used to simulate and analyze LED packages with different materials and structures. Using the theory of LED illuminance and uniformity, the illuminance of some structures is computed. The results show that the change of substrate material and structure can greatly impact heat dissipation, while changing array forms has little effect on heat dissipation. By improving the spatial distribution of the chip, the temperature superposition problem of the substrate is solved, and the illuminance and uniformity are improved while dissipating heat. The LED filaments of the combined, equidistant, chip-distribution mode have improved heat dissipation. The S-type equal difference has the highest illumination and high illumination uniformity.

An increase in internal pressure of a Roto-Jet pump is due to combined action of its impeller and rotating casing. Internal pressure of the pump chamber was determined according to outlet pressure of the impeller, and the influence of the rotary casing effect was ignored. To study the combined action mechanism of the rotating casing effect and impeller structure on the Roto-Jet pump, we used the open test bed of the Roto-Jet pump and four model pumps with impellers of different structures as research objects. We also conducted a comprehensive experimental study on the coupling mechanism between the rotating casing effect and impeller structure. Numerical calculation was performed to avoid the assumption of isotropic eddy viscosity, Reynolds stress linear pressure-strain model is selected, and the numerical calculation results are compared with the experimental results to verify its credibility. The results show that the rotating casing effect has multiple functions to reduce the friction loss of the disc, improve the pressure distribution inside the rotating casing, and increase the pump head. All scheme, pressure, and velocity fluctuations occur in the upstream and wake regions of the collecting pipe and the energy loss is concentrated in the upstream region. The difference in velocity distribution inside the collecting pipe is small and negligible. As long as the impeller and rotating casing continue to rotate synchronously, the liquid shear velocity at the same coordinate position of each scheme remains unchanged, and the liquid rotation angular velocity in the rotating casing is approximately 75% of the rotating casing which conforms to the rigid motion law. In the same scheme, the coefficient of uneven velocity inside the rotating casing gradually increases along the radial direction. The closer to the axis, the faster is the decrease of the peak tangential velocity and the velocity tends to be uniform. The size, shape, and position of the vortex core inside the rotating casing change constantly with various schemes. The distribution of vortex cores varies under each scheme. The front cover and rotating casing have a serious effect on the vortex core. The extremely poor analysis of the test results shows that the performance of the Roto-Jet pump is better when the closed impeller is rotated in synchronisation with the rotating casing. The advantages and disadvantages of each blade type can be determined according to the situation. The research results can exhibit the influence mechanism of the Roto-Jet pump shell effect. Selection of an impeller structure provides a reference.

Microglia activation contributes to Alzheimer’s disease (AD) etiology, and microglia migration is a fundamental function during microglia activation. The repressor element-1 silencing transcription factor (REST), a powerful transcriptional factor, was found to play a neuroprotective role in AD. Despite its possible role in disease progression, little is known about whether REST participates in microglia migration. In this study, we aimed to explore the function of REST and its molecular basis during microglia migration under Aβ1-42-treated pathological conditions. When treated by Aβ1-42 REST was upregulated through JAK2/STAT3 signal pathway in BV2 cells. And transwell coculture system was used to evaluate cell migration function of microglia-like BV2. Small interfering RNA (siRNA) targeting progranulin (PGRN) were delivered into BV2 cells, and results showed that PGRN functions to promote BV2 migration. REST expression was inhibited by sh-RNA, which induced BV2 cell migration obviously. On the contrary, REST was overexpressed by REST recombinant plasmid transfection, which repressed BV2 cell migration, indicating that REST may act as a repressor of cell migration. To more comprehensively examine the molecular basis, we analyzed the promoter sequence of PGRN and found that it has the potential binding site of REST. Moreover, knocking-down of REST can increase the expression of PGRN, which confirms the inhibiting effect of REST on PGRN expression. Further detection of double luciferase reporter gene also confirmed the inhibition of REST on the activity of PGRN promoter, indicating that REST may be an inhibitory transcription factor of PGRN which governs microglia-like BV2 cell migration. In conclusion, the present study demonstrates that transcription factor REST may act as a repressor of microglia migration through PGRN.

Compelling evidence from basic molecular biology has demonstrated the crucial role of microglia in the pathogenesis of Alzheimer’s disease (AD). Microglia were believed to play a dual role in both promoting and inhibiting Alzheimer’s disease progression. It is of great significance to regulate the function of microglia and make them develop in a favorable way. In the present study, we investigated the function of repressor element 1-silencing transcription factor (REST) in Aβ1-42-induced BV-2 cell dysfunction. We concluded that Aβ1-42 could promote type I activation of BV-2 cells and induce cell proliferation, migration, and proinflammation cytokine TNF-α, IL-1β, and IL-6 expression. Meanwhile, REST was upregulated, and nuclear translocalization took place due to Aβ1-42 stimulation. When REST was knocked down by a specific short hairpin RNA (sh-RNA), BV-2 cell proliferation, migration, and proinflammation cytokine expression and secretion induced by Aβ1-42 were increased, demonstrating that REST may act as a repressor of microglia-like BV-2 cell activation.

Chromatin undergoes drastic structural organization and epigenetic reprogramming during embryonic development. We present here a consistent view of the chromatin structural change, epigenetic reprogramming, and the corresponding sequence-dependence in both mouse and human embryo development. The two types of domains, identified earlier as forests (CGI-rich domains) and prairies (CGI-poor domains) based on the uneven distribution of CGI in the genome, become spatially segregated during embryonic development, with the exception of zygotic genome activation (ZGA) and implantation, at which point significant domain mixing occurs. Structural segregation largely coincides with DNA methylation and gene expression changes. Genes located in mixed prairie domains show proliferation and ectoderm differentiation-related function in ZGA and implantation, respectively. The chromatin of the ectoderm shows the weakest and the endoderm the strongest domain segregation in germ layers. This chromatin structure difference between different germ layers generally enlarges upon further differentiation. The systematic chromatin structure establishment and its sequence-based segregation strongly suggest the DNA sequence as a possible driving force for the establishment of chromatin 3D structures that profoundly affect the expression profile. Other possible factors correlated with or influencing chromatin structures, including transcription, the germ layers, and the cell cycle, are discussed for an understanding of concerted chromatin structure and epigenetic changes in development.

Stable matching of neurotransmitters with their receptors is fundamental to synapse function and reliable communication in neural circuits. Presynaptic neurotransmitters regulate the stabilization of postsynaptic transmitter receptors. Whether postsynaptic receptors regulate stabilization of presynaptic transmitters has received less attention. Here, we show that blockade of endogenous postsynaptic acetylcholine receptors (AChR) at the neuromuscular junction destabilizes the cholinergic phenotype in motor neurons and stabilizes an earlier, developmentally transient glutamatergic phenotype. Further, expression of exogenous postsynaptic gamma-aminobutyric acid type A receptors (GABAA receptors) in muscle cells stabilizes an earlier, developmentally transient GABAergic motor neuron phenotype. Both AChR and GABAA receptors are linked to presynaptic neurons through transsynaptic bridges. Knockdown of specific components of these transsynaptic bridges prevents stabilization of the cholinergic or GABAergic phenotypes. Bidirectional communication can enforce a match between transmitter and receptor and ensure the fidelity of synaptic transmission. Our findings suggest a potential role of dysfunctional transmitter receptors in neurological disorders that involve the loss of the presynaptic transmitter.

Because of the high-speed rotating impeller and the asymmetry volute, the flow parameters are strongly nonlinear in the screw centrifugal pump runner, in which the flow is multi-scale irregular and complex; moreover, the solid–liquid two-phase flow exacerbated the degree of nonlinear. To analyze the mechanism of solid–liquid two-phase flow and the evolution of the vortex in screw centrifugal pump, the model of the large- and meso-scale vortex evolution when the solid–liquid two-phase flow layered with the buoyancy effect is established, the flow structure and the change regulation of inner flow are revealed in the screw centrifugal pump, by the means of theoretical study of the inner flow states of the screw centrifugal pump, and the calculation of the internal flow field numerical simulation was performed. The research shows that the isodensity surface and isobaric surface are oblique which lead to the change in the vorticity; with both the fluid viscosity and the baroclinicity, the working vortex maintains an orderly flow form in time and space; the form of the vortex is mainly affected by the forces of fluid field, the vortex constantly reshapes the flow structure, the low-pressure areas form the positive vortex, while high-pressure areas are inclined to forming the reverse vortex, both the positive and reverse vortices always appear in pairs, which make the fluid take on the next states continuously; it is the difference of solid and liquid proportion in the solid–liquid two-phase flow that results in the phenomenon in which the flow tends to form different concentrations and stratifications, especially in rotating machinery; these phenomena are more common. With the effect of the rotating machinery impeller, the flow field becomes the flow with the vorticity, namely, forming the rotational flow, as well as the velocity difference between solid and liquid in the solid–liquid two-phase flow, and leads to that the fluid machinery internal velocity gradient and pressure gradient change is considerably great, which induces and motivates the generation and evolution of the vortex further.

Recent studies have suggested that 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) increases macrophage phagocytosis through adenosine monophosphate-activated protein kinase (AMPK). However, little information is available on the effects of AICAR on the clearance of apoptotic cells by macrophages, known as efferocytosis, which is essential in maintaining tissue homeostasis and resolving inflammation. AICAR increased p38 MAPK activation and the phagocytosis of apoptotic cells by macrophages, which were inhibited by the p38 MAPK inhibitor, SB203580, the TGF-beta-activated kinase 1 (TAK1) inhibitor, (5Z)-7-oxozeaenol, and siRNA-mediated knock-down of p38α. AICAR increased phosphorylation of Akt, but the inhibition of PI3K/Akt activity using LY294002 did not affect the AICAR-induced changes in efferocytosis in macrophages. CGS15943, a non-selective adenosine receptor antagonist, did not affect AICAR-induced changes in efferocytosis, but dipyridamole, an adenosine transporter inhibitor, diminished the AICAR-mediated increases in efferocytosis. AICAR-induced p38 MAPK phosphorylation was not inhibited by the AMPK inhibitor, compound C, or siRNA-mediated knock-down of AMPKα1. Inhibition of AMPK using compound C or 5'-iodotubercidin did not completely block AICAR-mediated increases in efferocytosis. Furthermore, AICAR also increased the removal of apoptotic neutrophils or thymocytes in mouse lungs. These results reveal a novel mechanism by which AICAR increases macrophage-mediated phagocytosis of apoptotic cells and suggest that AICAR may be used to treat efferocytosis-related inflammatory conditions.

OBJECTIVE: To establish equations for the estimation of glomerular filtration rates (eGFRs) based on serum creatinine (SCr) and/or serum cystatin C (SCysC) in Chinese patients with chronic kidney disease (CKD), and to compare the new equations with both the reference GFR (rGFR) and the literature equations to evaluate their applicability. METHODS: The 788 Chinese CKD patients were randomly divided into two groups, the training group and the testing group, to establish new eGFR-formulas based on serum CysC and to validate the established formulas, respectively. (99m)Tc-DTPA clearance (as the rGFR), serum Cr, and serum CysC were determined for all patients, and GFR was calculated using the Cockcroft-Gault equation (eGFR1), the MDRD formula (eGFR2), the CKD-EPI formulas (eGFR3, eGFR4), and the Chinese eGFR Investigation Collaboration formulas (eGFR5, eGFR6). The accuracy of each eGFR was compared with the rGFR. RESULTS: The training and testing groups' mean GFRs were 50.84±31.36 mL/min/1.73 m(2) and 54.16±29.45 mL/min/1.73 m(2), respectively. The two newly developed eGFR formulas were fitted using iterative computation: [Formula: see text] and [Formula: see text]. Significant correlation was observed between each eGFR and the rGFR. However, proportional errors and constant errors were observed between rGFR and eGFR1, eGFR2, eGFR4, eGFR5 or eGFR6, and constant errors were observed between eGFR3 and rGFR, as revealed by the Passing & Bablok plot analysis. The Bland-Altman analysis illustrated that the 95% limits of agreement of all equations exceeded the previously accepted limits of

In order to study the power capability of impeller and energy conversion mechanism of screw centrifugal pump, the methods of theoretical analysis and numerical simulation by computational fluid dynamics theory (CFD) were adopted, specifically discussing the conditions of internal flow such as velocity, pressure, and concentration. When the medium is sand-water two-phase flow and dividing the rim of the lines and wheel lines of screw centrifugal pump to segments to analyze energy conversion capabilities which along the impeller profile lines with the dynamic head and hydrostatic head changer, the results show that the energy of fluid of the screw centrifugal pump is provided by helical segment, and the helical segment of the front of the impeller has played the role of multilevel increasing energy; the sand-water two phases move at different speeds because the different force field and the impeller propeller and centrifugal effect. As liquid phase is the primary phase, the energy conversion is mainly up to the change of liquid energy, the solid phase flows under the wrapped action of liquid, and solid energy is carried out through liquid indirectly.

Physical exercise promotes motor skill learning in normal individuals and those with neurological disorders but its mechanism of action is unclear. We find that one week of voluntary wheel running enhances the acquisition of motor skills in normal adult mice. One week of running also induces switching from ACh to GABA expression in neurons in the caudal pedunculopontine nucleus (cPPN). Consistent with regulation of motor skills, we show that the switching neurons make projections to the substantia nigra (SN), ventral tegmental area (VTA) and ventrolateral-ventromedial nuclei of the thalamus (VL-VM). Use of viral vectors to override transmitter switching blocks the beneficial effect of running on motor skill learning. We suggest that neurotransmitter switching provides the basis by which sustained running benefits motor skill learning, presenting a target for clinical treatment of movement disorders.

Neurotransmitter switching in the adult mammalian brain occurs following photoperiod-induced stress, but the mechanism of regulation is unknown. Here, we demonstrate that elevated activity of dopaminergic neurons in the paraventricular nucleus of the hypothalamus (PaVN) in the adult rat is required for the loss of dopamine expression after long-day photoperiod exposure. The transmitter switch occurs exclusively in PaVN dopaminergic neurons that coexpress vesicular glutamate transporter 2 (VGLUT2), is accompanied by a loss of dopamine type 2 receptors (D2Rs) on corticotrophin-releasing factor (CRF) neurons, and can lead to increased release of CRF. Suppressing activity of all PaVN glutamatergic neurons decreases the number of inhibitory PaVN dopaminergic neurons, indicating homeostatic regulation of transmitter expression in the PaVN.