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Gas-liquid slug flow in horizontal pipes occurs frequently in industrial applications and is harmful to the piping systems owing to its intermittent structures. Therefore, it is essential to accurately describe the flow structure and investigate the flow mechanism. A non-intrusive fluorescence imaging method is employed to quantitatively reconstruct the slug bubble in a 15mm ID horizontal pipe in this article. Optical distortion correction method is firstly developed to improve the measurement accuracy of the instantaneous gas holdup, and then the time-average axial bubble velocity is simultaneously measured according to the feature matching of cross-sectional images. Additionally, the influence of phase superficial velocity on the interface stability is investigated through the phase holdup and the circumferential curvature distribution analysis. The typical three-dimensional structures of slug bubble are finally reconstructed through the velocity-based bicubic interpolation and median fusion algorithm. Previous correlations and reference instrumentation are used to evaluate the proposed method. Comparison results show that the method can effectively measure the flow parameters and reconstruct slug bubbles.

Determining the mechanism of senescence-associated pulmonary fibrosis is crucial for designing more effective treatments for chronic lung diseases. This study aimed to determine the following: whether Sirt1 and serum vitamin D decreased with physiological aging, promoting senescence-associated pulmonary fibrosis by activating TGF-β1/IL-11/MEK/ERK signaling, whether Sirt1 overexpression prevented TGF-β1/IL-11/MEK/ERK signaling-mediated senescence-associated pulmonary fibrosis in vitamin D-deficient (Cyp27b1

Mitochondria play an important role in cellular ATP production, reactive oxygen species regulation, and Ca

Accurate detection for pulverized coal injection (PCI) blockage and coke size distribution are effective for blast furnace (BF) operation. Nowadays, tuyere cameras have been applied in BF. However,...

The subject of energetic crystals has been significantly enriched in the past several decades, with the number rising rapidly. Meanwhile, some new types of crystals have appeared, such as energetic...

Jurassic coal samples from Liuhuanggou (LHG) and Wudong (WD) coal mines, Xinjiang Province, China, were selected for oxidative thermal energy experiments. A temperature-programmed experimental system measured the variation of gaseous products and the changes in thermal energy release with temperature. Thermokinetic parameters, namely the apparent activation energy (Ea) and pre-exponential factor (A), of the coal samples for four heating rates were determined using a thermogravimetric analyser. During the low-temperature oxidation stage, two samples had temperature curves characterised by their production levels of the index gas (CO); the temperature changes were approximately equal, but the critical temperatures differed. The WD sample produced less CO gas. However, the maximum and minimum exothermic strengths of the two samples had some similarities to the temperature change curves. The characteristic temperatures for the coal samples were discovered using different heating rates. For the WD sample, the characteristic temperature varied according to the heating rate, and the thermogravimetry (TG) and derivative TG curves of the samples lagged with an increase in the heating rate. The characteristic temperatures of the sample increased with the increase in the heating rate. Isokinetic analysis (the Flynn–Wall–Ozawa and the Kissinger–Akahira–Sunose models) was used to calculate the thermokinetic parameters of the sample. The range of the heating rates was 2 to 15 °C min−1 for oxygen concentration of 21 vol%, and the Ea of the samples decreased with the increase in the heating rate.

The lower flammability limit (LFL) of methane is 5 % in volume. Usually, in the relevant industry, the methane leakage monitoring threshold is set on the basis of the LFL from the perspective of safety precautions. When small amounts of other combustible gases coexist with methane, setting the monitoring threshold according to 5% vol may cause a large deviation and lead to a potential explosion accident. To investigate the effects of flammable gases and the relative humidity (RH) on the methane flammability limit behavior, the flammability limits of methane-air mixtures with the addition of gaseous fuels were experimentally measured in a standard cylindrical setup at various relative humidities. A theoretical model based on the adiabatic flame temperature method was employed to obtain reasonable estimates of the flammability limits of binary mixtures of methane and vapor. The combustion hazards of methane-air mixtures were evaluated. The results showed that both the LFL and the upper flammability limit (UFL) of methane were diminished with the addition of gaseous fuel at the same RH, while these parameters increased with an increase in the RH. The flammable range of methane-air mixtures was slightly narrowed by increasing the RH but was extended by the addition of gaseous fuel. The combustion hazard of methane increases as the volume fraction of added gases increases but drops with an increase in the RH. These phenomena were ascribed to the dual roles of water vapor and the influence of the added gaseous fuel on the initial stage of the methane-air chain reactions. The obtained data could supplement the flammability limits database and help to prevent potential explosion hazards.

Dual-task performance depends on both modalities (e.g., vision, audition, haptics) and task types (spatial or object-based), and the order by which different task types are organized. Previous studies on haptic and especially auditory–haptic attentional blink (AB) are scarce, and the effect of task types and their order have not been fully explored. In this study, 96 participants, divided into four groups of task type combinations, identified auditory or haptic Target 1 (T1) and haptic Target 2 (T2) in rapid series of sounds and forces. We observed a haptic AB (i.e., the accuracy of identifying T2 increased with increasing stimulus onset asynchrony between T1 and T2) in spatial, object-based, and object–spatial tasks, but not in spatial–object task. Changing the modality of an object-based T1 from haptics to audition eliminated the AB, but similar haptic-to-auditory change of the modality of a spatial T1 had no effect on the AB (if it exists). Our findings fill a gap in the literature regarding the auditory–haptic AB, and substantiate the importance of modalities, task types and their order, and the interaction between them. These findings were explained by how the cerebral cortex is organized for processing spatial and object-based information in different modalities.

Coal spontaneous combustion involves the process of functional group distribution and heat accumulation in coal. Therefore, analyzing the thermal reaction process of coal spontaneous combustion and...

Interleukin-12 (IL-12) and IL-23 are thought to have central roles in inflammation and are critical to pathologies associated with inflammation-induced bone disorders. The deletion of IL-12p40 (a common subunit of IL-12 and IL-23) can improve bone regeneration. However, the relative roles of IL-12 and IL-23 in bone disorders are largely unknown. Methods: Ectopic bone formation and skull defect models were established to evaluate the relative roles of IL-12 and IL-23 in inflammatory bone disorders. Differences in bone mass among WT, IL-12p35-/-, and IL-12p40-/- mice (young and elderly) were detected by micro-CT. Osteogenic and osteoclastic activities were explored using ELISA, qRT-PCR, and histological analysis. Moreover, the mechanisms by which IL-12 and IL-23 regulated the differentiation of BMMSCs and RAW264.7 cells were explored using Alizarin Red and tartrate-resistant acid phosphatase staining in vitro. Apilimod was used to inhibit IL-12 and IL-23 production in vivo. Results: Mice deficient in IL-12p40 promoted bone formation and protected against aging-related bone loss. By contrast, bone loss was aggravated in IL-12-/- mice, suggesting that IL-23 may play a dominant role in inflammation-related bone disorders. Mechanistically, IL-12 and IL-23 coupled osteogenesis and osteoclastic activities to regulate bone homeostasis and repair. IL-23 deficiency increased bone formation and inhibited bone resorption. Finally, apilimod treatment significantly improved bone regeneration and calvarial defect repair. Conclusion: These data collectively uncover a previously unrecognized role of IL-23 in skeletal tissue engineering. Thus, IL-23 can act as a biomarker to predict diseases and treatment efficacy, and apilimod can be used as an effective therapeutic drug to combat inflammatory bone disorders.

Adsorption of test substances on micromembrane filters during sample pretreatment before qualitative and quantitative analysis has greatly affected the accuracy of the measurement. In the present study, it was found that the adsorption rate of pyraclostrobin reached 77.7-100% when water samples of pyraclostrobin (1 mL) were filtered with polyethersulfone (PES) and nylon 6 filters. Therefore, the adsorption mechanisms were investigated from the kinetics, isotherms, and thermodynamics of the pyraclostrobin adsorption process, combined with Attenuated Total Reflection-Fourier Transform Infra-Red (ATR-FTIR) spectroscopy and X-ray Photoelectron Spectroscopy (XPS) analysis. The adsorption of pyraclostrobin on the PES micromembrane is chemical adsorption; while Nylon 6 is physical adsorption. However, pyraclostrobin adsorption onto surface sites of Nylon 6 micromembrane was mostly through physical monolayer. The π-π electron-donor-acceptor (EDA) between pyraclostrobin and PES may promote the adsorption of PES to pyraclostrobin, and hydrogen bonding between pyraclostrobin and Nylon 6 micromembrane may be involved in the adsorption. Our study also proved the addition of methanol and iodine solution was an effective strategy to reduce the adsorption effects and to increase the accuracy of the detection.

This project designed and created a large-scale pyrolysis incineration system that decomposes waste tributyl phosphate/kerosene (TBP/OK) solvent from the plutonium/uranium process (PU-REX) in the nuclear industry. This system consists of a suspension preparation system (SPS), a pyrolysis and ash discharge system (PADS), and a combustion furnace and gas treatment system (CGS). The preparation of a waste TBP/OK emulsified suspension in the SPS, continuous operation experiments of the PADS and CGS, and pyrolysis incineration experiments were conducted. The results show that the SPS achieved the automatic preparation and feeding of emulsified suspensions at 30 kg/h. The PADS decomposed 99.99% of the TBP/OK emulsified suspensions and fixed more than 99% of phosphorus. The CGS burned the pyrolysis gas without diesel oil and purified more than 99.995% of the radioactive nuclides. This system showed great feasibility, stability, continuity, and safety, proving the compatibility between multiple systems of this new design. This paper marks a significant step in pyrolysis incineration technology for the nuclear industry.

Primary health care has been emphasized as a pillar of China’s current round of health reforms throughout the previous decade. The purpose of this study is to analyze the accessibility of primary health care services in Beijing and to identify locations with a relative scarcity of health personnel. Seven ecological conservation districts, which are relatively underdeveloped, were selected in the study. The Gini coefficient and Lorenz curve, as well as the shortest trip time and modified two-step floating catchment area (M2SFCA) approach, are used to quantify inequalities in primary health care resources and spatial accessibility. The Gini coefficient of primary medical services was calculated as high as 0.705, showing a significant disparity in primary care services. A total of 81.22% of communities reached the nearest primary care institution within 15 min. The average accessibility of primary healthcare services, as measured by the number of health professionals per 1000 population, was 2.34 in the 1715 communities of seven ecological conservation districts. Three hundred and ninety-one communities (22.80%) were identified with relatively low accessibility. More primary health professionals should be allocated to Miyun, Mentougou, and Changping Districts. Overall, the primary healthcare resources were distributed unevenly in most districts. According to our study, expanding primary healthcare institutions, increasing the number of competent health professionals, and enhancing road networks will all be effective ways to increase spatial accessibility and reduce primary healthcare service disparity in Beijing.

Background: Chronic alcohol is one of the leading risk factors for male osteoporosis . Angiogenesis and osteogenesis coupled by type-H vessels coordinate the biological process of bone homeostasis to prevent osteopenia. It is unknown whether alcohol inhibits type-H-vessel-dependent bone formation. Aims: This study aimed to determine whether alcohol hampers proliferation and promotes aging of endothelial cells of type-H vessels, and whether alcohol inhibits the differentiation of bone marrow-mesenchymal stem cells (BM-MSCs) into osteoblasts through reducing the number and secretion of endothelial cells in type-H vessels. Materials and Methods: Two-month-old mice fed with alcohol liquid diet (28% of calories) or normal liquid diet for two months. The tibias were isolated and detected with X-ray and micro-CT. Paraffin-embedded or frozen tibial sections were prepared and used for immunohistochemical or immunofluorescence staining respectively in vivo . Human Umbilical Vein Endothelial Cells (HUVECs) were treated with different-concentrated alcohol for 12 hours. The conditioned medium of the above HUVECs cells was collected to culture human BM-MSCs, which were induced to differentiate into osteoblasts in vitro . Results: The alcoholic diet retarded the bone growth and lead to osteoporosis, impaired bone formation of osteoblasts, and decreased CD31 hi EMCN hi type-H-vessel formation through inhibiting proliferation and promoting aging of endothelial cells in mice. Alcohol treatment obviously increased the expression of p16, while significantly decreased the expression of Bmi-1, CDK6, Cyclin D, E2F1 and BMP2 compared to vehicle. Alcohol inhibited the differentiation of BM-MSCs into osteoblasts through reducing the BMP2 secretion of endothelial cells in type-H vessels. Conclusions: Alcoholic diet impaired CD31 hi EMCN hi type-H-vessel formation through inhibiting proliferation and promoting aging of endothelial cells via Bmi-1/p16 signaling, and inhibited the differentiation of BM-MSCs into osteoblasts through reducing the BMP2 secretion of endothelial cells in type-H vessels. It provides a basis for developing a new treatment strategy targeting aging endothelial cells of type-H-vessel to prevent alcoholic osteopenia.

SCOPE Liver plays a central role in maintaining lipid homeostasis which is dysregulated in non-alcoholic fatty liver disease (NAFLD) caused by overload of dietary fat, increase in lipid synthesis, and alteration of fatty acid oxidation in the liver. In this study, we aimed to investigate whether intermittent calorie restriction using a fasting-mimicking diet (FMD) is able to slow down the progression of NAFLD in mice. METHODS AND RESULTS This study analyzed the intervention activity of a FMD low in carbohydrate/protein but high in dietary fibers with a NAFLD mouse model induced by high-fat high-sucrose diet (HFHSD). Intermittent application of the FMD reduces HFHSD-induced obesity and glucose intolerance. The FMD decreases the size of adipocytes and elevates expression of lipolysis genes and HSL protein in white adipose tissue. HFHSD-induced lipid accumulation in the liver is reduced by the FMD, accompanied by a reduction of macrophage marker in the liver. RNA sequencing reveals that the expression of a number of genes involved in fatty acid oxidation is elevated by the FMD. CONCLUSION The findings indicate that intermittent application of the FMD can improve NAFLD, at least in part, through increased lipolysis in white adipose tissue and elevated fatty acid oxidation in the liver.

To study the similarities and differences in the macrocharacteristics of a coal seam during low-temperature oxidation at different regions of the same coal mine, six coal samples from the 13-1 seam were selected from Huainan, Anhui, China. The macroscopic spontaneous combustion characteristics, including the gaseous products and characteristic temperatures, during the low-temperature oxidation of samples from different regions of the same coal seam, were studied using a temperature-programmed test. The results revealed that the characteristic temperatures of the samples from the coal seam were close to each other, the critical temperature range was 70–80 °C, and the crack temperature range was 90–100 °C. The CO/O2 ratio varied considerably. Thus, the degree of incomplete oxidation reaction to release CO was different at different regions in the coal seam. Moreover, the variation in the CO/CO2 ratio of the samples from the coal seam was similar. A calorimeter (C80 Calvet, SETARAM, France) was adopted to explore the exothermic characteristics of the coal seam during low-temperature oxidation. The exothermic onset temperature of the samples from the coal seam was similar, with a range of 50.1–54.3 °C. Differences were observed in the total thermal energy released by oxidation at low temperature in the samples from the coal seam; however, the percentage of thermal energy release at low temperature and that during the entire oxidation process was similar. The changes in the apparent activation energy of coal specimens from the seam were similar. It was, and is, important to investigate the prediction and prevention technique of spontaneous combustion in regional coal seams.

Long noncoding RNAs (lncRNAs) have emerged as key regulators of cell differentiation and development. However, potential roles for lncRNAs in chondrogenic differentiation have remained poorly understood. Here we identify lncRNA ADAMTS9 antisense RNA 2, ADAMTS9-AS2, which controls the chondrogenic differentiation by acting as a competing endogenous RNA (ceRNA) in human mesenchymal stem cells (hMSCs). We screen out ADAMTS9-AS2 of undifferentiated and differentiated cells during chondrogenic differentiation by microarrays. Suppression or overexpression of lncRNA ADAMTS9-AS2 correlates with inhibition and promotion of hMSC chondrogenic differentiation, respectively. We find that ADAMTS9-AS2 can sponge miR-942-5p to regulate the expression of Scrg1, a transcription factor promoting chondrogenic gene expression. Finally, we confirm the function of ADAMTS9-AS2 to cartilage repair in the absence of transforming growth factor β (TGF-β) in vivo. In conclusion, ADAMTS9-AS2 plays an important role in chondrogenic differentiation as a ceRNA, so that it can be regarded as a therapy target for cartilage repair. Keywords: LncRNA ADAMTS9-AS2, MiR-942-5p, chondrogenesis, hMSCs, cartilage regeneration, chondrogenic differentiation, cartilage defect

AlSi12 cladding layer was fabricated on steel plate without zinc coating via cold metal transfer arc deposited technique. The wettability, morphologies, microstructures, and mechanical prop...

MicroRNAs play important roles in osteoporosis and show great potential for diagnosis and therapy of osteoporosis. Previous studies have demonstrated that miR-146a affects osteoblast (OB) and osteoclast (OC) formation. However, these findings have yet to be identified in vivo, and it is unclear whether miR-146a is related to postmenopausal osteoporosis. Here, we demonstrated that miR-146a knockout protects bone loss in mouse model of estrogen-deficient osteoporosis, and miR-146a inhibits OB and OC activities in vitro and in vivo. MiR-146a-/- mice displayed the same bone mass as the wild type (WT) but exhibited a stronger bone turnover than the WT did under normal conditions. Nevertheless, miR-146a-/- mice showed an increase in bone mass after undergoing ovariectomy (OVX) compared with those subjected to sham operation. OC activities were impaired in the miR-146a-/- mice exposed to estrogen deficiency, which was diametrically opposite to the enhanced bone resorption ability of WT. Macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) from a bone microenvironment affect this extraordinary phenomenon. Therefore, our results implicate that miR-146a plays a key role in estrogen deficiency-induced osteoporosis, and the inhibition of this molecule provides skeleton protection. © 2019 American Society for Bone and Mineral Research.

Coal spontaneous combustion is characterized by high-temperature oxidation and microscopic mechanisms. These are essential aspects to understand when attempting to control or prevent spontaneous combustion. Three fresh bituminous coal samples were collected for experimentation from Huainan, China. X-ray diffraction and Fourier-transform infrared spectrometry were conducted to determine the microscopic characteristics of coal during high-temperature oxidation. The mineral structures and functional groups were ascertained to ensure that the original structural characteristics of the coals were obtained. Thermogravimetry–differential scanning calorimetry was used to divide the high-temperature oxidation into four substages and obtain detailed exothermic characteristics. The heat energy release exhibited a positive correlation with an increase in temperature. Moreover, to investigate the relationship between the functional groups and their exothermic characteristics, correlation analysis was conducted for describing the quantitative phenomena within the four oxidation stages. The results revealed that the oxygen-containing groups were initially the most active and reactive among the 14 types of functional groups. The most rapid stage of spontaneous combustion, in which should be the most cautious and aware of risks, was the oxygen adsorption and mass gain stage because the heat energy output increased rapidly and passed this stage, thus leading to dangerous and possibly unrecoverable situations.

Gravity casting has been applied extensively. Cavity will occur in the casting and form shrinkage cavity in solidification due to volume reduction and lowering of liquid metal level, which will affect casting quality. The formation process of shrinkage cavity cannot be directly observed and needs to be displayed by using the numerical simulation method. The smoothed particle hydrodynamics (SPH) method is a pure Lagrange method with no grids and has now been applied in casting numerical simulation, but the prediction model of the shrinkage cavity in gravity casting solidification based on the SPH method has not been reported. In this paper, the mathematical model for temperature field (including latent heat treatment) and shrinkage cavity prediction in solidification is established based on the SPH method. The correctness for the temperature field (including latent heat treatment) is validated by computing temperature field in the solidification of an L-shaped aluminum alloy casting, and correctness for the prediction of shrinkage cavity is validated by computing the shrinkage cavity in the solidification of a cylindrical steel casting.

To investigate the effects of ethylene on methane-air explosions on a macro-to-micro level, the corresponding explosion and flame emission spectral behaviors were experimentally studied in a 20-L spherical chamber. The maximum explosion pressure, maximum pressure rising rate, and explosion duration were tested. The emission spectra of the key intermediates OH*, H* and CH2O* were obtained synchronously by using a photomultiplier-monochromator method. The detailed mechanism of GRI-Mech 3.0 was employed to analyze the kinetic reactions in the explosion process. A comprehensive analysis was performed by correlating the explosion parameters and emission spectral data. The results indicated that the added C2H4 would enhance the explosion of the fuel-lean methane-air mixture and attenuate the explosion of the fuel-rich mixture. It first promotes and then weakens the explosion of the stoichiometric methane-air mixture on the basis of the added volume fraction. The behavior of free radicals is well in accordance with the explosion parameters. The added C2H4 promotes the accumulation of the intermediates. Moreover, the variation in the production rate for the dominant reactions to generate the intermediates, caused by the addition of C2H4, directly results in a change in the average rising rate and maximum emission intensity of the intermediates.

Research on the micro- and macrocharacteristics of different metamorphic degrees of coal helps improve the control and protection techniques used during spontaneous combustion. Nine coals with different properties were thoroughly investigated in this study. Fourier transform infrared spectroscopy and a self-designed temperature-programmed oil bath experimental system were adopted to analyze the molecular structure and macrocharacteristic parameters of the spontaneous combustion of coal. Additionally, the influence of particle size on spontaneous combustion was considered. Various functional groups were employed as microcharacteristic parameters to capture the principal active groups in oxidation. The gas production rate, oxygen consumption rate, gas concentration, heat energy release rate, and characteristic temperatures were evaluated as macrocharacteristic parameters to investigate the changes in coal during oxidation. The results establish that the microcharacteristics of coal molecules determine the degree of spontaneous combustion based on intrinsic properties and that changes in the macrocharacteristics of the spontaneous combustion of coal reflect the microstructural changes. The contents of the hydroxyl groups, carbonyl groups, alkyl ether and aryl ether in the coal molecules gradually decrease with the metamorphic increase. Oxygen-containing functional groups have higher reactivities and easily react with oxygen, causing the macroparameters, such as the oxygen consumption rate, the gas generation rate and the heat energy release rate, to consistently decrease with the increase of the metamorphic degree. Small-particle-size coal molecules have more active aliphatic hydrocarbons, oxygen-containing functional groups and a larger specific surface area, increasing the chances of adsorbing the oxygen of active groups and promoting the reaction between coal and oxygen. The experimental results indicate that coal samples with higher metamorphic degrees or larger sizes exhibit lower tendencies toward spontaneous combustion. Evaluation of the spontaneous combustion of coal based on a temperature-programmed oil bath experimental system is of great practical importance for preventing the spontaneous combustion of coal during storage, processing and utilization and can serve as a convenient reference for production safety in mining applications.

Tin bronze cladding layer with thin thickness and large width was fabricated on thin steel sheet by cold metal transfer arc deposited technique. The morphology, microstructure and mechanical proper...

In mining, coal is crushed into particles of various sizes. The size of these reactant particles affects the combustion risk profiles in mine safety, thus affecting industrial safety considerations. Therefore, this study explores the influence of particle size on hazardous gas emissions during the high-temperature oxidation of coal. A custom-designed and built high-temperature experimental system was developed and implemented. This practical experiment was conducted with the aforementioned system to analyze three coal samples from Huainan, Anhui Province, China. The gas concentration data were recorded for carbon monoxide, carbon dioxide, alkanes, and alkenes, with six different particle sizes, and covered a temperature range of 30 to 500 °C. As the oxygen consumption rate and normal temperatures are equally strong influential factors of spontaneous combustion, the oxygen consumption rate was simultaneously captured using the indicator gas growth rate method to determine the five characteristic temperatures was captured using the indicator gas growth rate analytical method. The five characteristic temperatures for the six particle sizes were determined as follows: critical, crack, active, speedup, and ignition.

Low-density lipoprotein cholesterol (LDL-C) is the hallmark of atherosclerotic cardiovascular diseases. The hepatic LDL receptor (LDLR) plays an important role in clearance of circulating LDL-C. PCSK9 facilitates degradation of LDLR in the lysosome and antagonizing PCSK9 has been successfully used in the clinic to reduce blood LDL-C level. Here we identify a new player that modulates LDLR interaction with PCSK9, thus controlling LDLR degradation and cholesterol homeostasis.The blood LDL-C and cholesterol levels were analyzed in mice with hepatic deletion of Paqr3 gene. The half-life of LDLR was analyzed in HepG2 cells. The interaction of PAQR3 with LDLR and PCSK9 was analyzed by co-immunoprecipitation and immunofluorescent staining.The blood LDL-C and total cholesterol levels in the mice with hepatic deletion of Paqr3 gene were significantly lower than the control mice after feeding with high-fat diet (p 0.001 and p 0.05 respectively). The steady-state level of LDLR protein is elevated by Paqr3 knockdown/deletion and reduced by PAQR3 overexpression. The half-life of LDLR protein is increased by Paqr3 knockdown and accelerated by PAQR3 overexpression. PAQR3 interacts with the β-sheet domain of LDLR and the P-domain of PCSK9 respectively. In addition, PAQR3 can be localized in early endosomes and colocalized with LDLR, PCSK9 and LDL. Mechanistically, PAQR3 enhances the interaction between LDLR and PCSK9.Our study reveals that PAQR3 plays a pivotal role in controlling hepatic LDLR degradation and blood LDL-C level via modulating LDLR-PCSK9 interaction.

PIP5k1β is crucial to the generation of phosphotidylinosotol (4, 5)P2. PIP5k1β participates in numerous cellular activities, such as B cell and platelet activation, cell phagocytosis and endocytosis, cell apoptosis, and cytoskeletal organization. In the present work, we aimed to examine the function of PIP5k1β in osteoclastogenesis and osteogenesis to provide promising strategies for osteoporosis prevention and treatment. We discovered that PIP5k1β deletion in mice resulted in obvious bone loss and that PIP5k1β was highly expressed during both osteoclast and osteoblast differentiation. Deletion of the gene was found to enhance the proliferation and migration of bone marrow-derived macrophage-like cells to promote osteoclast differentiation. PIP5k1β−/− osteoclasts exhibited normal cytoskeleton architecture but stronger resorption activity. PIP5k1β deficiency also promoted activation of mitogen-activated kinase and Akt signaling, enhanced TRAF6 and c-Fos expression, facilitated the expression and nuclear translocation of NFATC1, and upregulated Grb2 expression, thereby accelerating osteoclast differentiation and function. Finally, PIP5k1β enhanced osteoblast differentiation by upregulating master gene expression through triggering smad1/5/8 signaling. Therefore, PIP5k1β modulates bone homeostasis and remodeling.

As an efficient underwater cutting method, flux cored arc cutting is not clear in its mechanism because it is difficult to directly observe the process. In this paper, we studied the mechanism of flux cored arc cutting in air first. The impact of cutting parameters was studied by cutting workpiece’s edge and observing it with a high-speed camera system. Secondly, a sandwich structure was designed to observe the underwater cutting process. The characteristics of air and underwater cutting were analyzed and compared, and it showed that the arc moved up and down while moving forward with the cutting torch in both circumstances. Based on the arc movement characteristics and the underwater circumstance, a numerical simulation of the underwater cutting process was conducted. The simulation results showed that different cutting parameters led to different cutting mode and kerf forming. The numerical results of temperature distribution and kerf shape were consistent to the experimental data, which revealed the cutting mechanism. This work is significant for further process optimization and cutting automation.

MIL-125(Ti)-derived titanium oxides, a functionalized cake-like 3D material, is becoming increasingly attractive to researchers. In this work, COOH functionalized anatase TiO2 (TiO2@C) was prepared by one-step calcination method. And the TiO2@C, as a novel catalyst, was used to accelerate electron transfer from As(III) to Cr(VI) for simultaneous Cr(VI) reduction and As(III) oxidization in aqueous solution. The results showed that the addition of TiO2@C greatly accelerates the coupled As(III)/Cr(VI) reaction. This reaction is further enhanced at acidic pH and higher concentrations of material. Furthermore, the mutual conversion is equally sensitive to ion initial concentration. Accordingly, a new microscopic redox reaction process of As(III) and Cr(VI) was proposed, which was first made clear of the mutual redox via XPS and FTIR analysis. To be specific, the carboxyl on anatase not only offers As(III) and Cr(VI) ions binding sites, but also initiates the electron transfer from As(III) to Cr(VI) on the solid surface. While the cake-like geometry with high surface area serves for the electron transfer pathways. This unparalleled reaction mechanism enlighten us on a new field of COOH functionalized catalyst used for the coupled removal of As(III)/Cr(VI).

Low circulating 25-hydroxyvitamin D (25(OH)D) levels associate with obesity, diabetes, and hyperlipidemia, but the underlying mechanisms remain uncertain. As energy-dense diet contributes to these disorders, this study investigates whether diet could impair vitamin D metabolism.Compared with control chow-fed mice, high fat diet (HFD)-fed mice show lower serum 25(OH)DThese findings suggest that diet-induced elevation of circulating cholesterol, glucose, and insulin reduces serum 25(OH)D

In E-commerce, vouchers are important marketing tools to enhance users' engagement and boost sales and revenue. The likelihood that a user redeems a voucher is a key factor in voucher distribution decision. User-item Click-Through-Rate (CTR) models are often applied to predict the user-voucher redemption rate. However, the voucher scenario involves more complicated relations among users, items and vouchers. The users' historical behavior in a voucher collection activity reflects users' voucher usage patterns, which is nevertheless overlooked by the CTR-based solutions. In this paper, we propose a Deep Multi-behavior Graph Networks (DMBGN) to shed light on this field for the voucher redemption rate prediction. The complex structural user-voucher-item relationships are captured by a User-Behavior Voucher Graph (UVG). User behavior happening both before and after voucher collection is taken into consideration, and a high-level representation is extracted by Higher-order Graph Neural Networks. On top of a sequence of UVGs, an attention network is built which can help to learn users' long-term voucher redemption preference. Extensive experiments on three large-scale production datasets demonstrate the proposed DMBGN model is effective, with 10% to 16% relative AUC improvement over Deep Neural Networks (DNN), and 2% to 4% AUC improvement over Deep Interest Network (DIN). Source code and a sample dataset are made publicly available to facilitate future research., 9 pages, 5 figures, accepted full paper SIGKDD'21 applied data science track

Background Introduction Multiple sclerosis(MS) is a common complication of uncontrolled or excessive neuroinflammation and autoimmunity disease. Advances in high-throughput technologies and available bioinformatics tools make it possible to evaluate different expressions in the whole genome instead of focusing on a limited number of genes. MethodsMaterials and methods Two public available databases GSE81279 and GSE21942 of multiple sclerosis samples were downloaded analyzed by CIBERSORT. Gene Ontology (GO) and KEGG pathway analysis based on GSEA was performed by cluster profile software to reveal the regulatory relations among genes and provided a systematic understanding of the functional differentially expressed genes at the transcriptional level.GSE81279 was used to validate the association between core genes and clinical information. ResultsFor immune cells, T-cell gamma delta and monocyte showed a trend toward reduction. The connection between the most prominent GO terms showed HBB, GATA2, NAA35, TCL1A, SECISBP2L, CLC, AGPAT5, CCR3, LTF, MALAT1, MS4A3 were significantly differentially expressed in MS. Gene set enrichment result was presented CDKN1A, DDB2, MME HMGN1, XPC, RELA for subsequent analysis.GSE81279 showed five types of immune cells revealed important links with MS. GSEA and layered KEGG analyses revealed that enrichment of immune response-related in primary immunodeficiency, it also consistent with previous studies. We got 10 genes, including HLA-DR, IL7R, HBB, TNFRSF1A, CYP27B1, NR1H3, IL2RA, TNFR1, BAFF, and CYP2R1 had close connections to clinical features. ConclusionsOur study identifies immune cell infiltration with microarray data of the plasma in MS by using CIBERSORT analysis, we also provide novel information for further study of genes of multiple sclerosis.

Fat storage and mobilization in adipose tissue play a central role in energy metabolism and are directly linked to the development of obesity. Upon starvation, fat is mobilized from adipose tissue by lipolysis, a process by which triglycerides are hydrolyzed to free fatty acids to be used as an energy source in skeletal muscles and other tissues. However, how lipolysis is activated by starvation is not fully known. In this study, we demonstrate that PAQR11, a member of the progesterone and AdipoQ receptor family, regulates starvation-mediated lipolysis. Paqr11-deleted mice are resistant to high-fat diet-induced obesity. Paqr11 deletion promotes lipolysis in white adipose tissue, characterized by increased phosphorylations of hormone-sensitive lipase (HSL) and perilipin 1 (PLIN1) and elevated serum levels of glycerol and free fatty acids. PKA activity and cAMP levels in white adipose tissue are also increased by Paqr11 deletion, accompanied by accelerated protein degradation of phosphodiesterase 4D (PDE4D). Mechanistically, PAQR11 decreases the interaction of PDE4D with SKP1-CUL1-FBXO2 E3 ligase complex, thus modulating the polyubiquitination/degradation of PDE4D. Fasting decreases the expression of the Paqr11 gene, and starvation-induced lipolysis in white adipose tissue is enhanced by Paqr11 deletion, while insulin-mediated suppression of lipolysis is not affected. Collectively, these results reveal that PAQR11 regulates lipolysis of adipose tissue and affects high-fat diet-induced obesity., Highlights • Paqr11 deletion promotes lipolysis in epididymal white adipose tissue. • PAQR11 modulates cAMP level by altering protein degradation of PDE4D. • PAQR11 affects the interaction of PDE4D with SKP1-CUL1-FBXO2 E3 ligase complex. • PAQR11 regulates starvation-induced lipolysis in adipose tissue.