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Excessive manganese (Mn) exposure gives rise to various neurological disorders, including motor dysfunction and cognitive impairment. Microglia-mediated neuroinflammation plays an essential role in the pathogenesis of Mn neurotoxicity. However, the underlying mechanisms have not been fully clarified. Immunoproteasome is a specialized proteasome. Recent studies have shown that immunoproteasome, especially catalytic subunit PSMB8, is highly associated with various neurological diseases. Whether PSMB8 is involved in Mn-neurotoxicity is still unknown. In this study, in vivo and in vitro models were established, and our data showed that Mn exposure upregulated the expression and activity of PSMB8. Selective inhibition of PSMB8 mitigated neuroinflammation with reduced microglial activation and fewer TNF-α, iNOS, and CCL12 production in Mn-treated mice and BV2 cells. Learning and memory tests and Golgi staining further confirmed that inhibition of PSMB8 alleviated Mn-induced recognition memory impairments and synapse deficits. Besides, we found that blocking of PERK signaling inhibited Mn-induced elevation of PSMB8. And inhibition of PSMB8 reduced the phosphorylation of NF-κB p65. Together, our data demonstrated that PSMB8 played an essential role in microglia-mediated neuroinflammation upon Mn exposure, and the underlying mechanisms may be via PERK/NF-κB pathways. These results provide a novel target for the prevention and treatment of Mn-neurotoxicity. [Display omitted] • Manganese upregulated the expression and activity of PSMB8. • Inhibition of PSMB8 mitigated microglial activation. • Inhibition of PSMB8 alleviated Mn-induced recognition impairment. • Blocking of PERK signaling reduced Mn-induced elevation of PSMB8. [ABSTRACT FROM AUTHOR]

The HfO films grown on Pt substrates were deposited at different temperatures by RF magnetron sputtering. The crystal quality of HfO film increased with the increasing deposition temperature. Typical bipolar resistive switching (RS) characteristics were observed in prepared samples. The sample deposited at 100 °C showed the best RS performance with large ON/OFF ratio, concentrated distribution of switching voltages and good reliability. Reset-first RS behavior was observed for the 300 °C deposited sample due to the high density of defects and the diffusion of Cu in the film. The distinct RS behaviors are closely related to the microproperties of the films. The possible switching mechanisms were discussed. [ABSTRACT FROM AUTHOR]

Lactobacillus fermentum temperate bacteriophage φ PYB5 uses endolysin Lyb5 and holin Hyb5 to burst the host cell. Previous results showed that expression of Lyb5 in Escherichia coli caused host cell lysis slowly, leading us to suppose that Lyb5 could pass the cytoplasmic membrane partly. In this work, the function of a putative signal peptide (SP Lyb5 ) at the N-terminal of Lyb5 was investigated. In E. coli , the cell adopted a spherical shape during induction of Lyb5 protein, while morphological changes were not observed during expression of the SP Lyb5 truncation, indicating that the SP Lyb5 motif may serve as a functional signal peptide. However, SP Lyb5 was not proteolytically cleaved at the predicted site during the translocation of Lyb5, and the expressed Lyb5 protein appeared in the cytoplasm, cytoplasmic membrane and periplasm fractions with the same molecular mass. Similar results were obtained using Lactococcus lactis as a host to express Lyb5. These results indicated that SP Lyb5 could direct Lyb5 to the periplasm in a membrane-tethered form, and then release it as a soluble active enzyme into the periplasm. In addition, SP Lyb5 could also drive the fused NucleaseB protein to the extracytoplasm environment in E. coli as well as in L. lactis . We proposed that in Gram-negative and Gram-positive hosts SP Lyb5 acted as a signal–anchor–release domain, which was firstly identified here by experimental evidences in lactic acid bacteria phages. The application of signal–anchor–release domain for endolysin export in bacteriophages infecting Gram-positive and Gram-negative hosts was discussed. [ABSTRACT FROM AUTHOR]

Wool fiber diameter (WFD) is the most important economic trait of wool. However, the genes specifically controlling WFD remain elusive. In this study, the expression profiles of skin from two groups of Gansu Alpine merino sheep with different WFD (a super-fine wool group [FD = 18.0 ± 0.5 μm, n= 3] and a fine wool group [FD=23.0±0.5μm, n=3]) were analyzed using next-generation sequencing–based digital gene expression profiling. A total of 40 significant differentially expressed genes (DEGs) were detected, including 9 up-regulated genes and 31 down-regulated genes. Further expression profile analysis of natural antisense transcripts (NATs) showed that more than 30% of the genes presented in sheep skin expression profiles had NATs. A total of 7 NATs with significant differential expression were detected, and all were down-regulated. Among of 40 DEGs, 3 DEGs (AQP8, Bos d2, and SPRR) had significant NATs which were all significantly down-regulated in the super-fine wool group. In total of DEGs and NATs were summarized as 3 main GO categories and 38 subcategories. Among the molecular functions, cellular components and biological processes categories, binding, cell part and metabolic process were the most dominant subcategories, respectively. However, no significant enrichment of GO terms was found (corrected P-value >0.05). The pathways that were significantly enriched with significant DEGs and NATs were mainly the lipoic acid metabolism, bile secretion, salivary secretion and ribosome and phenylalanine metabolism pathways (P < 0.05). The results indicated that expression of NATs and gene transcripts were correlated, suggesting a role in gene regulation. The discovery of these DEGs and NATs could facilitate enhanced selection for super-fine wool sheep through gene-assisted selection or targeted gene manipulation in the future. [ABSTRACT FROM AUTHOR]

Mounting studies have been showed that long-term macrolides used in patients with asthma could improve the lung function and symptoms. However, a large number of studies have reported inconclusive results. The aim of this meta-analysis was to investigate the effect of macrolide antibiotics in patients with asthma. We have performed a search in PubMed, Embase, China National Knowledge Internet (CNKI), and Wanfang databases. The weighed mean difference (WMD) or standardized mean difference (SMD) was used to evaluate the pooled effect. Statistical analysis was performed by STATA 11.0 software. Totally 1306 patients were included in the meta-analysis. The overall results indicated that statistically significance of long-term macrolides therapy in patients with asthma on forced expiratory volume in 1 s (FEV1) (WMD: 0.11, P < 0.01), peak expiratory flow (PEF) (SMD: 0.25, P = 0.001), airway hyper-responsiveness (AHR) (SMD: 0.90, P = 0.04), forced vital capacity (FVC) (WMD: 0.18, P = 0.05) and FEV1/FVC (WMD: 1.93, P < 0.001), but no statistically significance on FEV1/predict, FVC/predict, symptom scores, quality of life scores (QOL), reliever inhaler puffs per 24 h, and cell counts in sputum and blood. The subgroup analysis indicated macrolides could increase FEV1 and PEF in Caucasian and Asian, decrease AHR in Caucasian, while cells counts of sputum improvement among Asian. Therefore, the study suggested that long-term marolides therapy in asthma may improved the FEV1, PEF, AHR, FVC, FEV1/FVC and cells counts in sputum, but it can't improve other lung function (FEV1/predict and FVC/predict) and clinical outcomes (such as symptom, quality of life etc.). [ABSTRACT FROM AUTHOR]

The effects of Cu doping and annealing process on crystal structure and resistive switching (RS) characteristics of HfO 2 films fabricated by RF magnetron sputtering were investigated. The chemical compositions of the films were characterized by X-ray photoelectron spectroscopy. The defects induced by Cu dopants played an important role on the RS characteristics. The enhanced ON/OFF ratio and reduced switch voltages were demonstrated for the doped film. The further annealing process for HfO 2 :Cu film not only decreased the switch voltages but also improved the distribution of the switch voltages of the film. The RS behaviors of HfO 2 :Cu films can be well explained by space charge limited current (SCLC) effect. [ABSTRACT FROM AUTHOR]

The impact of Au-doping on the resistive switching properties of a Cu/HfO 2 /Pt resistive random access memory (RRAM) device is investigated. The significantly enhanced performances are achieved in the Cu/HfO 2 : Au/Pt device, including low set voltages, improved uniformity of switching parameters, enough ON/OFF ratio. This performance improvement in Cu/HfO 2 : Au/Pt is clarified to the suppressed stochastic formation of oxygen vacancy conducting filaments in the HfO 2 film by Au O bond effect. The validity of the trivalent dopants in future application of HfO 2 -based RRAM devices is also identified. [ABSTRACT FROM AUTHOR]

Highlights: [•] The formation energies of oxygen vacancy in Au doped HfO2 are calculated. [•] Au doping suppresses the randomicity of oxygen vacancy filaments’ formation. [•] The Cu/HfO2: Au/Pt shows superior resistive switching properties. [ABSTRACT FROM AUTHOR]

Key message: Genetic basis of grain yield heterosis relies on the cumulative effects of dominance, overdominance, and epistasis in maize hybrid Yuyu22. Abstract: Heterosis, i.e., when F hybrid phenotypes are superior to those of the parents, continues to play a critical role in boosting global grain yield. Notwithstanding our limited insight into the genetic and molecular basis of heterosis, it has been exploited extensively using different breeding approaches. In this study, we investigated the genetic underpinnings of grain yield and its components using 'immortalized F' and recombinant inbred line populations derived from the elite hybrid Yuyu22. A high-density linkage map consisting of 3,184 bins was used to assess (1) the additive and additive-by-additive effects determined using recombinant inbred lines; (2) the dominance and dominance-by-dominance effects from a mid-parent heterosis dataset; and (3) the various genetic effects in the 'immortalized F' population. Compared with a low-density simple sequence repeat map, the bin map identified more quantitative trait loci, with higher LOD scores and better accuracy of detecting quantitative trait loci. The bin map showed that, among all traits, dominance was more important to heterosis than other genetic effects. The importance of overdominance/pseudo-overdominance was proportional to the amount of heterosis. In addition, epistasis contributed to heterosis as well. Phenotypic variances explained by the QTLs detected were close to the broad-sense heritabilities of the observed traits. Comparison of the analyzed results obtained for the 'immortalized F' population with those for the mid-parent heterosis dataset indicated identical genetic modes of action for mid-parent heterosis and grain yield performance of the hybrid. [ABSTRACT FROM AUTHOR]

Substantially high rate of glycolysis, known as the Warburg effect, is a well-known feature of cancers, and emerging evidence suggests that it supports cancerous proliferation/tumor growth. Phosphoglycerate mutase (PGAM), a glycolytic enzyme, is commonly up-regulated in several cancers, and recent reports show its involvement in the Warburg effect. Here, a comprehensive analysis shows that PGAM is acetylated at lysines 100/106/113/138 in its central region, and a member of the Sirtuin family (class III deacetylase), SIRT2, is responsible for its deacetylation. Over-expression of SIRT2 or mutations at the acetylatable lysines of PGAM attenuates cancer cell proliferation with a concomitant decrease in PGAM activity. We also report that the acetyltransferase PCAF (p300/CBP-associated factor) interacts with PGAM and acetylates its C-terminus, but not the central region. As prior evidence suggests that SIRT2 functions as a tumor suppressor, our results would provide support for the mechanistic basis of this activity. [ABSTRACT FROM AUTHOR]

In the process of policy financing guaranteeing help to SMEs to make innovations in green technologies, multiple parties continue to play strategic games for their interests. Evolutionary game theory is a practical tool for analyzing multi-agent strategies, which can help us to explore how policy financing guarantees help to SMEs to achieve effective credit enhancement. This paper constructs a four-party evolutionary game model among SMEs, banks, guarantee agencies, and the government, and obtains four evolutionary stable strategies by analyzing various players' replicator dynamics. In addition, we carry out numerical simulations on the key parameters affecting the stability of the game system. The findings suggest that keeping the fixed risk-ratio between guarantee agencies and banks constant reduces the government's financial burden and strengthens the re-guarantee system's construction at the initial stage of SME financing, which can indirectly increase the enthusiasm for cooperation between banks and guarantee agencies. The interest subsidy policy is more effective in promoting SMEs' compliance and bank–guarantee cooperation in the short term. Meanwhile, the government should increase the supervision of defaulting SMEs and cooperate with financial institutions to improve the credit system for SMEs. [ABSTRACT FROM AUTHOR]

• A cold rolling effectively improves the adhesion between Ti substrate and TNAs. • The influence mechanism of the microstructure of the Ti matrix on the growth process of TNAs and the adhesion between TNAs and the matrix was studied in detail. • The improved finer grain sizes and increased dislocation density may reduce the F contents and release the stress at the interface of TNAs and Ti, thereby improving its adhesion to the base. TiO 2 nanotube arrays (TNAs) prepared by the traditional methods are prone to peeling off from the underlying titanium due to the weak interfacial adhesion between the nanotube layers and Ti substrates, which greatly restricts their applications. Here, 2.5 mm titanium plates are cold rolled to the Ti sheets of various thicknesses by controlling the cold-rolling reduction process. Ti sheets are then anodized in an electrolyte that was composed of water, NH 4 F, and ethylene glycol. It is discovered that after the cold-rolling process, not only are the pore sizes of the nanotubes smaller, but also the tube length is longer, indicating different growth behavior for the rolled Ti sheets. The results of XRD, EBSD, and metallographic microstructure analysis revealed mechanical anchorage at grain boundaries and decreased F contents, which leads to release stress at the TNAs/Ti interface. Most probably the released stress, finer grain sizes and increased dislocation density are responsible for the improved adhesion. [ABSTRACT FROM AUTHOR]

In this study, the bioinspired laminated composites with alternating soft Al layers and hard SiCp/Al were fabricated through the tape casting followed by pressure infiltration. In-situ bending and digital image correlation technology (DIC) analysis were carried out on the laminated composites. The results showed that the uniform layers of SiCp/Al and Al were obtained with the thickness of 30 μm and 10 μm, respectively. The interfaces between layers had an intimated combination. The bending deformation process of the laminated composites could be divided into three stages, i.e., crack initiation, crack stable diffusion and crack propagation instability. During deformation, the laminated structure changed the state of strain and strain distribution, further restricted the development of the crack, and the whole materials presented a stepped fracture. This study provides support for preparation and fracture process analysis of biomimetic layered composites prepared by tape casting. [ABSTRACT FROM AUTHOR]

Hemorrhage progression in deep intracerebral hemorrhage (ICH) involves not only the growth of parenchymal hematoma but also an increase in intraventricular hemorrhage (IVH). The search for methods that predict both the increased risk of parenchymal hematoma and IVH growth is warranted. We conducted a retrospective cohort study at multiple centers. Participants with deep ICH were enrolled from January 2018 to December 2021. Prediction models based on logistic regression analysis included clinical as well as routine radiographic and radiomics variables, separately or in combination. The performance of each model was evaluated using discrimination measures (e.g., area under the curve [AUC]). Evaluation of clinical utility was performed using decision curve analysis (DCA). Overall, 647 individuals across 4 stroke centers were included. A total of 429 (66%) patients from 3 centers were assigned to the primary cohort and 218 (34%) from another center were placed in the validation cohort. Multivariate analysis showed that the Glasgow Coma Scale score, baseline ICH volume, IVH, blend sign, and radiomics score were associated with hemorrhage progression in the primary cohort. The clinical-radiomics model (AUC = 0.852 and 0.835) improved the prediction performance of hemorrhage progression compared to the Noncontrast computed tomography signs model (AUC = 0.666 and 0.618) in both the primary and validation cohorts, with similar results in the decision curve analysis curves. The clinical-radiomics model outperformed the routine Noncontrast computed tomography signs model in predicting the progression of deep ICH. The clinical benefit of screening patients using this model may assist in risk stratification. [ABSTRACT FROM AUTHOR]

Based on first-principles calculations, the electronic and magnetic properties of As doped wurtzite ZnO were studied. The results indicate that the As dopant can induce the magnetic moment of about 1.0 μ, the coupling between the magnetic moments induced by As is ferromagnetic, for which the p-p interaction between As and O atoms should be responsible. [ABSTRACT FROM AUTHOR]

Abstract: Based on first-principles calculations, (Sb, N) codoped ZnO are investigated. We find that SbZn–4NO have lower formation energy and can form p-type conduction with smaller hole effective mass. In comparation to monodoping of Sb, SbZn–4NO complex can form better p-type conductivity than SbZn–2VZn, which may be strongly compensated by SbZn defect and result in a decrease of p-type conduction. So we inferred that (Sb, N) codoping in ZnO under O-poor condition should be a realizable candidate of p-type conduction. [Copyright &y& Elsevier]

Highlights: [•] ZAO thin films have been deposited on PMMA substrates using facing target sputtering system. [•] The lowest resistivity of 2.4×10−3 Ωcm with a figure of merit value of 3.42×10−3 Ω−1 was obtained. [•] The intrinsic band gap of ZAO thin film is 3.40eV. [•] The carrier transport of the films is mainly limited by grain boundary scattering. [ABSTRACT FROM AUTHOR]

Highlights: [•] ZAO thin films have been deposited on PET substrates using facing target sputtering system. [•] The lowest resistivity of 1.3×10−3 Ωcm with a sheet resistance of 29Ω/□. [•] The relative visible transmittance above 93% in the visible region. [•] With increased working power, the carrier concentration has little change. [ABSTRACT FROM AUTHOR]

In traditional Chinese medicine, there is a long history that curcuma longa L is used to treat distending pain of chest and belly, arthralgia of shoulder and arm aggravated by cold. Traditional Chinese medicine holds that breast cancer is caused by cold congelation, stagnation of qi and blood stasis. It is usually treated with some pungent and warm Chinese herbs, such as Curcuma longa L and Curcuma zedoaria (Christm.) Rosc, which are effective in promoting blood circulation for removing blood stasis, activating qi-flowing and relieving pain. Curcumin, a polyphenolic compound, is the main pharmacological component extracted from the rhizome of Curcuma longa L. Modern pharmacological studies have found that curcumin has many kinds of pharmacological activities of anti-inflammatory, anti-tumor, anti-angiogenesis, anti-metastasis and anti-multidrug resistance. To explore the mechanism of curcumin and Glioma-associated oncogene homolod-1 (Gli1) on invasion and metastasis of triple negative breast cancer (TNBC) cells through the Hedgehog (Hh)/Gli signaling pathway. The effect of curcumin on TNBC cells was detected by colony formation, wound healing and transwell assay. Breast cancer stem cells (BCSCs) were cultured in serum-free medium and its stemness was detected by flow cytometry and subcutaneous xenografted tumor assay. The formation of mammospheres was used to detect the effect of curcumin and GANT61 (Gli inhibitor)on the formation ability of BCSCs. Gli1 overexpressed was conducted in MDA-MB-231 cells by lentivirus vector HBLV-h-Gli1-3xflag-ZsGreen-PURO. RT-qPCR and Western blot were detected the mRNA and protein level of genes of Hh pathway, Epithelial-mesenchymal transition (EMT) and stemness. The nuclear localization and expression of Gli1 was observed by laser confocal microscope scanning. Co-IP was investigated the key genes interacted with Gli1. The abilities of proliferation, invasion, migration and the formation of mammospheres in TNBC cells were inhibited by curcumin. Furthermore, curcumin reduced the invasion and migration abilities in stable Gli1-overexpressing MDA-MB-231 cell. Moreover, curcumin down-regulated the expression of genes related Hh pathway, EMT and stemness in MDA-MB-231 mammospheres. Observation of laser confocal microscope showed that Gli1 were expressed mainly in nucleus in MDA-MB-231 adherent cells and completely in nucleus in BCSCs, which was significantly reduced in the nucleus and cytoplasm after curcumin treatment. Besides, our results suggested that vimentin was interacted with Gli1. Curcumin can inhibit the proliferation and metastasis of TNBC cells, EMT and characteristics of BCSC by Hedgehog/Gli1 pathway. [Display omitted] • Curcumin can inhibit the proliferation and metastasis of TNBC cells, EMT and characteristics of BCSCs. • Curcumin inhibited Hh pathway by reducing the expression of Gli1 in nucleus.Gli1may be an effective target of curcumin. • Dysregulation of Gli1 induced the expression of vimentin, thus effecting the process of EMT and characteristics of MDA-MB-231 BCSCs. [ABSTRACT FROM AUTHOR]

Climbing on a vertical ship hull underwater while using surface cleaning tools remains a great challenge for climbing robots. In this study, we design a negative-pressure adsorptive underwater climbing robot using the Bernoulli negative-pressure generation mechanism. Computational fluid dynamics modelling is performed with a sliding mesh to explore the optimal adhesion performance. The factors that influence the adsorptive force are investigated, such as the contra-rotating propellers (CRPs) speed and gap distance between the bottom plate of the robot and the adsorbate, and their cause and effect are established by taking into consideration the fluid pressures and velocities for the Bernoulli negative-pressure effect on the bottom plate of the robot. Based on the optimal parameters determined from the numerical simulations, a prototype adsorptive climbing robot is fabricated and tested in a water pool. Comparisons with the experimental results show that the numerical model predicts the adsorptive force with an accuracy of 94.1%. The proposed method and the findings reported in this paper are valuable in guiding the design of negative-pressure adsorptive parameters for climbing robots, and will significantly improve the robot's capability to precisely adjust the adsorptive force by driving the CRP motor accordingly. • Designed an underwater robot by Bernoulli's theorem to generate adsorptive force. • Robot adapts to various adsorbates, with contactless, large and controllable force. • Factors that affect the optimal adsorptive force were studied. • The sliding mesh method was performed to reveal the formation process of the force. • A numerical model to estimate the force was validated with the experimental data. [ABSTRACT FROM AUTHOR]

Biodegradable and absorbable sutures have been widely used in surgical procedures. However, for the repair of ligament and tendon injures, the biodegradable suture cannot provide sufficient mechanical support to close the wound for a long period of time which is important to completely heal the tissue. Herein, we develop a simple method that makes a surface coating to prolong the degradation of the suture in vivo. Polylactic acid (PLLA) and Polycaprolactone (PCL) were successfully coated to a commercial degradable polydioxanone (PDO) suture in this study, which was confirmed by Fourier transform infrared spectra (FTIR). Scanning electron microscopy (SEM) was used to observe the smooth surface of the coated sutures. Moreover, live/dead assay of human fibroblasts after co-culturing with the modified/unmodified sutures showed fairly good cellular activity. In vivo study demonstrates the degradation properties of sutures were significantly changed after the surface coating. The raw suture exhibited the fastest degradation in 12 weeks, showing significantly decline in mechanical strength. Interestingly, the PCL-coated suture was able to maintain more than 20% of its original tensile strength after 12 weeks' implantation. In addition, in vivo results of PCL-coated sutures also showed less inflammatory cell infiltration and less surface inflammation. These findings indicate the one step suture-coating method could be feasibly for the development of clinical equipment. [Display omitted] • PLLA and PCL were coated on PDO suture through a one-step method. • The surface coatings were demonstrated no cytotoxic to human fibroblasts. • Prolonged degradation time and mechanical strength were demonstrated both in vitro and in vivo. • The material is promising for medical applications. [ABSTRACT FROM AUTHOR]

The time-dependent behavior of power-law fluid has a significant influence on the grouting effects of reinforcing loose gravel soil. In this paper, based on basic rheological equations and the time-dependent behavior of rheological parameters (consistency coefficient and rheological index), rheological equations and penetration equations of time-dependent power-law fluid are proposed. Its penetration grouting diffusion mechanism for reinforcing loose gravel soil was then theoretically induced. A set of indoor experimental devices for simulating penetration grouting was designed to simulate the penetration grouting of power-law fluid with different time-dependent behaviors for reinforcing loose gravel soil. Then, relying on the COMSOL Multiphysics platform and Darcy's law, three-dimensional numerical calculation programs for this mechanism were obtained using secondary-development programming technology. Thus, the numerical simulations of the penetration grouting process of power-law fluid with different time-dependent behaviors for reinforcing loose gravel soil were carried out. This theoretical mechanism was validated by comparing results from theoretical analyses, indoor experiments, and numerical simulations. Research results show that the three-dimensional numerical calculation programs can successfully simulate the penetration diffusion patterns of a time-dependent power-law fluid in loose gravel soil. The theoretical calculation values and numerical simulation values of the diffusion radius obtained from this mechanism are closer to indoor experimental values than those obtained from the penetration grouting diffusion theory of power-law fluid without considering time-dependent behavior. This mechanism can better reflect the penetration grouting diffusion laws of a power-law fluid in loose gravel soil than the theory, which can provide theoretical support and guidance for practical grouting construction. [ABSTRACT FROM AUTHOR]

A drug delivery system was specifically designed for the treatment of rheumatoid arthritis (RA) by local percutaneous administration and the nano-controlled release of methotrexate (MTX). The release behavior of MTX from the synthesized MTX-mSiO2@PDA system was investigated in vitro and in vivo. The obtained results show that after 48 h, twice as much MTX (cumulative amount) is released at pH 5.5 than at pH 7.4. This suggests that the MTX-mSiO2@PDA system exhibits a good pH sensitivity. In vitro local percutaneous administration experiments revealed that the cumulative amount of MTX transferred from MTX-mSiO2@PDA to pH 5.0 receptor fluid through the whole skin was approximately three times greater than the amount transferred to pH 7.4 receptor fluid after 24 h. Moreover, in vivo experiments conducted on a complete induced arthritis (CIA) model in DBA/1 mice demonstrated that the thickness of a mouse's toes decreases to nearly 65% of the initial level after 27 days of local percutaneous MTX-mSiO2@PDA administration. Compared to the mice directly injected with MTX, those administered with MTX-mSiO2@PDA by local percutaneous application exhibit much lower toe thickness deviation, which indicates that the latter group experiences a better cure stability. Overall, these results demonstrate that the local percutaneous administration of MTX delivery systems characterized by nano-controlled release may play an important role in RA therapy. [ABSTRACT FROM AUTHOR]

Three putative promoter regions were identified preceding the nisZ gene in Lactococcus lactis HSM-22. To investigate their function in the control of nisZ biosynthesis, green fluorescence protein (GFP) was adopted as probe to determine activities of the three promoters. The results showed that PnisZ-0 containing two sets of the −35 and −10 regions exhibited the same maximum activity as promoter PnisZ-2 containing the putative promoter region near the start codon. However, the GFP expression level directed by PnisZ-0 was twofold higher than that found with PnisZ-2 under low-dose nisin, indicating that promoter PnisZ-1 distant from the start codon could be important in response to the inducer nisin. Then, Pnis-2 was randomized to develop functional promoters through the degenerate oligonucleotide approach in L. lactis. 35 inducible promoters and 14 constitutive promoters were obtained, covering 3-5 logs of expression levels in small increments of activity. Sequence analysis revealed that base changes in both consensus sequence and spacing sequence resulted in remarkable decrease of promoter activity, while the sequence outside −35 and −10 regions would influence the promoter function radically. The functional promoters were evaluated for the efficiency and stability to control β-galactosidase (Gal) expression in L. lactis. High correlation was obtained between the Gal activity and promoter strength, suggesting that promoters developed here have the potential for fine tuning gene expression in L. lactis. [ABSTRACT FROM AUTHOR]

Selection of recombinant inbred lines (RILs) from elite hybrids is a key method in maize breeding especially in developing countries. The RILs are normally derived by repeated self-pollination and selection. In this study, we first investigated the accuracy of different models in predicting the performance of F hybrids between RILs derived from two elite maize inbred lines Zong3 and 87-1, and then compared these models through simulation using a wider range of genetic models. Results indicated that appropriate prediction models depended on genetic architecture, e.g., combined model using breeding value and genome-wide prediction (BV+GWP) has the highest prediction accuracy for high V/ V ratio (>0.5) traits. Theoretical studies demonstrated that different components of genetic variance were captured by different prediction models, which in turn explained the accuracy of these models in predicting the F hybrid performance. Based on genome-wide prediction model (GWP), 114 untested F hybrids possibly having higher grain yield than the original F hybrid Yuyu22 (the single cross between Zong3 and 87-1) have been identified and recommended for further field test. [ABSTRACT FROM AUTHOR]

Abstract: In the liver, glucokinase (GCK) facilitates hepatic glucose uptake during hyperglycemia and is essential for the regulation of a network of glucose-responsive genes involved in glycolysis, glycogen synthesis, and lipogenesis. To better understand the consequences of changes in response to a liver-specific deficiency of GCK function, we examined the expression profiles of genes involved in glucose metabolism in the liver, pancreas, muscle and adipose tissue in heterozygous liver-specific Gck knockout (Gck w/−) mice. Our results showed that with the development of a liver GCK deficiency, significant decreases in the mRNA levels for insulin receptor and Glut2 were observed in the liver, and HkII in muscle, while glucagon mRNA increased markedly in the pancreas. The levels of circulating glucagon hormone levels increased with increased mRNA levels. Depite a decrease in muscle HkII levels, the hexokinase activity level did not change. Our findings suggest that in liver-specific Gck w/– mice, peripheral tissues use different strategies to tackle with hyperglycemia even at a young age. By identifying the specific changes that occur in different tissues at an early stage of glucokinase deficiency, potentially we can develop interventions to prevent further progression to diabetes. [Copyright &y& Elsevier]

The clinical relevance of coronary artery ectasia (CAE) is poorly understood. We investigated the prevalence, potential predictors, and prognostic significance of CAE in patients with atherosclerotic coronary artery disease. Consecutive patients undergoing percutaneous coronary intervention (PCI) from January 2016 to December 2018 were included and followed up for 1 year. CAE was diagnosed as an abnormal dilation >1.5-fold the diameter of adjacent normal segments on angiography. A total of 590 patients with CAE were identified from 36 790 patients undergoing PCI (overall rate of CAE: 1.6%). In multivariate analysis, variables including body mass index >30 kg/m2 (risk ratio, RR: 2.413, P =.018), ever-smoking (RR: 1.669, P <.001), hypertension (RR: 1.221, P =.025), acute myocardial infarction at admission (RR: 1.343, P =.004), no diabetes (RR:.810, P =.023), previous myocardial infarction (RR: 1.545, P <.001), no left main disease (RR:.632, P =.008) and multiple-vessel disease (RR: 1.326, P =.001), increased C-reactive protein (RR: 1.006, P =.012) were predictors of CAE. The incidence of adverse cardiovascular outcomes did not differ significantly between patients with or without CAE (P =.203). CAE is not uncommon among patients undergoing PCI in this cohort study. The presence of CAE vs its absence had no significant impact on 1-year clinical outcomes after PCI. [ABSTRACT FROM AUTHOR]

Superconducting quantum computing is currently one of the most promising platforms for universal quantum information processing. The readout resonator is an essential integral part of a superconducting qubit, while its size is much larger compared to the Josephson junction. We propose and realize a new readout resonator using space-filling curves, specifically Hilbert space-filling curves. We introduce the frequency analysis method and demonstrate a qubit sample, in which the Hilbert-space-filling-curves resonator (HSFCR) is used to read out the qubit states. We also propose to fabricate the HSFCRs and Josephson junctions simultaneously in the same processes of E-beam lithography and E-beam evaporation. Our design reduces the resonator area sufficiently and, thus, will help to improve the integration of superconducting qubits, as well as to design other superconducting quantum devices. [ABSTRACT FROM AUTHOR]

The organization of maize ( Zea mays L.) germplasm into genetically divergent heterotic groups is the foundation of a successful hybrid maize breeding program. In this study, 94 CIMMYT maize lines (CMLs) and 54 United States germplasm enhancement of maize (GEM) lines were assembled and characterized using 1,266 single nucleotide polymorphisms (SNPs) with high quality. Based on principal component analysis (PCA), the GEM lines and CMLs were clearly separated. In the GEM lines, there were two groups classified by PCA corresponding to the heterotic groups 'stiff stalk' and 'non-stiff stalk'. CMLs did not form obvious subgroups by PCA. The allelic frequency of each SNP differed in GEM lines and CMLs. In total, 3.6% alleles (46/1,266) of CMLs are absent in GEM lines and 4.4% alleles (56/1,266) of GEM lines are absent in CMLs. The performance of F1 plants ( n = 654) produced by crossing between different groups based on pedigree information was evaluated at the breeding nurseries of two CIMMYT stations. Genomic estimated phenotypic values of plant height and days to anthesis for a testing set of 45 F1 crosses were predicted based on the training data of 600 F1 crosses using a best linear unbiased prediction method. The prediction accuracy benefitted from the adoption of the markers associated with quantitative trait loci for both traits; however, it does not necessarily increase with an increase in marker density. It is suggested that genomic selection combined with association analysis could improve prediction efficiency and reduce cost. For hybrid maize breeding in the tropics, incorporating GEM lines which have unique alleles and clear heterotic patterns into tropically adapted lines could be beneficial for enhancing heterosis in grain yields. [ABSTRACT FROM AUTHOR]

• The longer alkyl side chain length of ionic liquids, the stronger interaction between ionic liquids and bovine serum albumin. • The cytotoxicities of 1-alkyl-3-methylimdazolium dicyanamide to MCF-7 cells increased with the alkyl chain length. • The inhibition to bacterial growth augmented when the alkyl chain length increased. In this study, the behavior of 1-alkyl-3-methylimidazolium dicyanamide ionic liquids (ILs) with ethyl, butyl, hexyl, octyl, and decyl side-chains was evaluated to gain a deeper insight into the potential hazards posed by ILs to the environment and organisms. The effects of the alkyl side-chain length on the interactions between the ILs and bovine serum albumin (BSA), the cytotoxicity and antibacterial performance of the ILs was evaluated. The BSA binding ability of the ILs increased with increasing alkyl side-chain length, and the binding constants of the ILs increased from 1.80 L/mol for 1-ethyl-3-methylimidazolium dicyanamide to 196 L/mol for 1-decyl-3-methylimidazolium dicyanamide. IL binding with BSA was a spontaneous process initiated by hydrophobic forces. This was confirmed using circular dichroism spectra, dynamic light scattering measurements and molecular docking simulations. The results of the cytotoxicity and antimicrobial activity of ILs demonstrated that the increase in alkyl side-chain length increased IL toxicity. The effects of the alkyl side-chain length of 1-alkyl-3-methylimidazolium tetrafluoroborate ILs on the interactions between ILs and BSA and cytotoxicity of the ILs were also evaluated. Furthermore, we demonstrated that tetrafluoroborate-based ILs were more toxic than dicyanamide-based ILs. Herein, we thoroughly describe the effects of the alkyl side-chain length on the properties of ILs and provide background information for future studies on the properties of carbon dots fabricated using ILs as precursors. [ABSTRACT FROM AUTHOR]

• Ultrasonic assisted enzymatic degumming (UAED) is developed to refine ARA oil. • UAED is optimized by response surface methodology with Box- Behnken design. • Fatty acid composition of oil by UAED is similar to those of enzymatic degumming (ED) and crude oil. • In addition to oxidation stability, the quality of oil by UAED is superior to that of oil by ED and crude oil. Ultrasound assisted enzymatic method was applied to the degumming of arachidonic acid (ARA) oil produced by Mortierella alpina. The conditions of degumming process were optimized by response surface methodology with Box- Behnken design. A dephosphorization rate of 98.82% was achieved under optimum conditions of a 500 U/kg of Phospholipase A 1 (PLA 1) dosage, 2.8 mL/100 g of water volume, 120 min of ultrasonic time, and 135 W of ultrasonic power. The phosphorus content of ultrasonic assisted enzymatic degumming oil (UAEDO) was 4.79 mg/kg, which was significantly lower than that of enzymatic degumming oil (EDO, 17.98 mg/kg). Crude Oil (CO), EDO and UAEDO revealed the similar fatty acid compositions, and ARA was dominated (50.97 ~ 52.40%). The oxidation stability of UAEDO was equivalent to EDO and weaker than CO, while UAEDO presented the strongest thermal stability, followed by EDO and CO. Furthermore, aldehydes, acids and alcohols were identified the main volatile flavor components for the three oils. The proportions of major contributing components such as hexanal, nonanal, (E)-2-nonanal, (E, E)-2,4-decadienal, (E)-2-nonenal and aldehydes in UAEDO and EDO were all lower than CO. Overall, Ultrasound assisted enzymatic degumming proved to be an efficient and superior method for degumming of ARA oil. [ABSTRACT FROM AUTHOR]

[Display omitted] • [Ch][Bit] and [Ch][Dhc] changed the natural structure of BSA. • The esterase-like activity of BSA decreased after adding [Ch][Br] and [Ch][I]. • The order of cytotoxicity: [Ch][Dhc] < [Ch][Bit] < [Ch][I] < [Ch][Br] < [Ch][Cl]. Choline-based ionic liquids (ILs) have been widely applied because of their good biocompatibility. Herein, the toxicity of choline-based ILs containing different anions was studied by UV–vis absorption spectra, fluorescence spectra, MTT assays and antibacterial experiments. The results explained that choline chloride ([Ch][Cl]) had no obvious effect on the conformation of bovine serum albumin (BSA), while the conformation could be slightly changed by choline bromide ([Ch][Br]). In the presence of choline iodide ([Ch][I]), choline bitartrate ([Ch][Bit]) and choline dihydrogen citrate ([Ch][Dhc]), the conformation of BSA changed significantly. The quenching mechanisms of [Ch][Bit] and [Ch][Dhc] were static quenching procedure, while there were charge transfer quenching and static quenching for [Ch][I]. ILs combined with BSA in spontaneous manner driven by hydrogen bond and van der Waals force, which was proved by thermodynamic constants and molecular docking. The toxicity of the five ILs to mammalian cells and bacteria came to a similar conclusion. [Ch][Cl] had little toxicity to cells, which was less than [Ch][Br] and [Ch][I]. [Ch][Bit] and [Ch][Dhc] were more toxic. These results provide more information to understand the effect of anions on choline-based ILs, in order to find low toxic choline-based ILs that can be used in biological and pharmaceutical fields. [ABSTRACT FROM AUTHOR]

The herbicide 4-chloro-2-methylphenoxy acetic acid (MCPA) is widely used to control the spread of broad-leaved weeds in agricultural soils, though it remains unclear how tomato plants cope with the phytotoxic effects of MCPA at the molecular level. In this study, RNA-seq and Illumina MiSeq were used to sequence bacterial communities in tomato rhizosphere soils treated with MCPA and the phosphate-solubilizing bacterial strain N3. The results showed that MCPA induced abnormal growth of lateral roots in tomato seedlings and reduced uptake of the nutrients N, P, and K as well as the hormone (ABA and GA3) levels. Inoculation with strain N3 increased nutrient uptake by roots and increased levels of the hormones ABA, ZEA, and JA in tomato seedlings and also increased the abundance of the phyla Proteobacteria and Gemmatimonadetes in soil under MCPA treatment. GO functional groups in which differentially expressed genes (DEGs) are involved included DNA binding transcription factor activity, transcriptional regulator activity, enzyme inhibitor activity, and cell wall biogenesis. The highest numbers of DEGs are annotated to ribosome, photosynthesis, and carbon metabolism categories. Our findings provide valuable information for the application of strain N3, which is beneficial for reducing the toxic effect of MCPA on vegetable plants. [Display omitted] • MCPA inhibited main root growth and induced abnormal lateral root formation in tomato. • Strain N3 greatly increased nutrient uptake in roots, especially Fe3+ by 3.58-fold. • MCPA decreased levels of plant hormones (ABA, JA, and GA3), but increased the ZEA. • MCPA reduced the relative abundance of Cyanobacteria-chloroplasts in substrate soils. • Strain N3 can abate the toxic effect of MCPA to improve tomato seedling growth. [ABSTRACT FROM AUTHOR]

Ma-xing-shi-gan-tang (MXSGT), which is documented in the Treatise on Febrile Diseases and is a therapeutic drug, is a well-known classic prescription in China and has been widely studied. Previous studies have shown that MXSGT has various pharmacological activities, including anti-influenza virus activity, and ameliorates microvascular hyperpermeability and inflammatory reactions. However, no study has reported the effect of MXSGT in the treatment of bacterial pneumonia. In this study, the potential inhibition of MXSGT against the virulence of S. pneumoniae by targeting PLY was investigated. First, HPLC analysis was used to determine the main components of MXSGT. Then PLY protein was constructed and used for hemolysis assay and western blot to test the ability of MXSGT to inhibit PLY activity, production and widowed characteristics. The growth curve of S. pneumoniae was drawled with or without MXSGT treatment. In addition, the inhibition of MXSGT against PLY-mediated A549 cell death was examined by cytotoxicity assay. Finally, the mouse experiment was used to verify the effect of MXSGT on mouse lungs. This work has discovered that MXSGT, a TCM prescription, is an effective inhibitor of PLY, an important virulence factor that is essential for S. pneumoniae pathogenicity. MXSGT inhibits the oligomerization of PLY without affecting S. pneumoniae growth and PLY production. In addition, experimental MXSGT treatment was effective against S. pneumoniae infection both in vitro and in vivo. These findings directly demonstrate the potential mechanism of the Chinese herbal formula MXSGT in the treatment of pneumococcal disease and provide additional evidence for promotion of the wide use of MXSGT in the clinic. [Display omitted] [ABSTRACT FROM AUTHOR]

HfO x /Cu/HfO x structures with Ti electrodes were fabricated to investigate the resistive switching characteristics. Stable and uniform switching behaviors can be observed for HfO x /Cu/HfO x sample except the few cycles at the beginning. XPS depth profile of the structure was carried out to explore the role of interface layer on chemical composition of HfO x film and the defects in the films were analyzed. In addition, the resistance in LRS was insensitive to device area. The processes of growth and dissolution of conductive filaments in HfO x film during switching cycles were investigated. The undissolved filaments in the bottom part of HfO x film promoted the growth of filaments in the subsequent set process. As the fixed V o s filaments and stable residual Cu filaments which can act as a precursor in upper and bottom part of the sample were formed, excellently uniform distribution of switching parameters can be obtained. Meanwhile, good endurance and retention properties can be observed for HfO x /Cu/HfO x sample. The migration of V o s and diffusion of Cu atoms under electric field were both responsible for the resistive switching behavior for HfO x /Cu/HfO x sample, and the underlying physical model of conductive filaments was proposed to illustrate the switching mechanism of HfO x /Cu/HfO x sample. • Interface modulation of HfO x /Cu/HfO x /Ti sample was analyzed by XPS depth profile. • Excellent uniformity of switching parameters were observed for the prepared sample. • Stable residual Cu filaments greatly improved the reliability of HfO x sample. • Oxygen vacancies and diffused Cu atoms both contributed to switching behavior. [ABSTRACT FROM AUTHOR]

d -Tagatose is a low-calorie sweetener with health benefits. To produce d -tagatose from lactose, a metabolic engineering Lactiplantibacillus plantarum was constructed. The galactokinase gene gal K was inactivated and the original promoter of β-galactosidase gene lac LM was replaced by a strong lactose/galactose-inducible promoter P lacLM-35-10 in Lpb. plantarum WCFS1. Subsequently, the l -arabinose isomerase gene Ara A derived from Lactobacillus casei SDMCC050286 was over-expressed. A recombinant strain with the potential of d -tagatose production was obtained. Its galactose metabolism pathway was blocked, and β-galactosidase activity was increased by 5.4-folds. Meanwhile, the heterogeneous l -arabinose isomerase was highly expressed in this strain. The optimal conditions for d -tagatose production by resting cells of the recombinant strain were at 65 °C and pH 7.5. Furthermore, the conversion rate of d -tagatose from 175 g/L lactose reached 33% at 56 h. This study verified the feasibility of one-pot production of d -tagatose from lactose by engineering strain of Lpb. plantarum , thereby laying down the foundation for industrial usage of lactose. • An engineering Lpb. plantarum was constructed to produce d -tagatose from lactose. • Leloir pathway was blocked and β-galactosidase activity was increased 5.4-folds. • The l -arabinose isomerase from Lb. casei was highly expressed. • The conversion rate of d -tagatose from 175 g/L lactose reached 33% by using the strain. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is resistant to current immunotherapy. This poor outcome mainly results from the immunosuppressive characteristics of tumor microenvironment (TME). Accumulating evidence indicates that some chemotherapy agents trigger immunogenic cell death (ICD), providing a promising strategy to remodel the immunosuppressive TME. The role of Plumbagin (PLB, a naphthoquinone compound from Plumbago zeylanica L.) as the ICD inducer for HCC cells was confirmed in this study. Dihydrotanshinone I (DIH, a phenanthraquinone compound of Salvia miltiorrhiza) functioned as the ICD enhancer by generating the reactive oxygen species (ROS). A poly(D,L-lactic- co -glycolic acid) (PLGA)-based nanoparticle (NP) was used to co-encapsulate PLB, DIH and NH 4 HCO 3 (a pH sensitive adjuvant). This NP was further coated with the mannose-inserted erythrocyte membrane to produce a nanoformulation. This nanoformulation significantly increased the half-life and tumor targeting of two drugs in orthotopic HCC mice, generating chemo-immunotherapeutic effects for reversal of immunosuppressive TME. Consequently, the biomimetic nanoformulation loaded with low doses of PLB and DIH achieved significantly longer survival of HCC mice, without causing toxic signs. Our study demonstrates a promising strategy for remodeling the immunosuppressive TME of liver cancer. Co-delivery of Plumbagin and Dihydrotanshinone I using biomimetic NPs for reversal of immunosuppressive TME in HCC. [Display omitted] • Plumbagin functions as an ICD inducer against HCC. • Dihydrotanshinone I generates ROS to enhance the ICD effects of PLB. • A biomimetic co-nanoformulation reverses the immunosuppressive tumor microenvironment of HCC. [ABSTRACT FROM AUTHOR]

Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) plays an essential role in Tau and Aβ pathology closely related to Alzheimer's disease (AD). Accumulative evidence has demonstrated DYRK1A inhibition is able to reduce the pathological features of AD. Nevertheless, there is no approved DYRK1A inhibitor for clinical use as anti-AD therapy. This is somewhat due to the lack of effective and safe chemotypes of DYRK1A inhibitors. To address this issue, we carried out in silico screening, in vitro assays and in vivo efficacy evaluation with the aim to discover a new class of DYRK1A inhibitors for potential treatment of AD. By in silico screening, we selected and purchased 16 potential DYRK1A inhibitors from the Specs chemical library. Among them, compound Q17 (Specs ID: AO-476/40829177) potently inhibited DYRK1A. The hydrogen bonds between compound Q17 and two amino acid residues named GLU239 and LYS188, were uncovered by molecular docking and molecular dynamics simulation. The cell-based assays showed that compound Q17 could protect the SH-SY5Y human neuroblastoma cell line from okadaic acid (OA)-induced injury by targeting DYRK1A. More importantly, compound Q17 significantly improved cognitive dysfunction of 3 × Tg-AD mice, ameliorated pathological changes, and attenuated Tau hyperphosphorylation as well as Aβ deposition. In summary, our computational modeling strategy is effective to identify novel chemotypes of DYRK1A inhibitors with great potential to treat AD, and the identified compound Q17 in this study is worthy of further study. Graphic abstract [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Gangba sheep as a famous breed of Tibetan sheep, its wool color is mainly white and black. Gangba wool is economically important as a high-quality raw material for Tibetan blankets and Tibetan serge. However, relatively few studies have been conducted on the wool color of Tibetan sheep. Results: To fill this research gap, this study conducted an in-depth analysis of two populations of Gangba sheep (black and white wool color) using whole genome resequencing to identify genetic variation associated with wool color. Utilizing PCA, Genetic Admixture, and N-J Tree analyses, the present study revealed a consistent genetic relationship and structure between black and white wool colored Gangba sheep populations, which is consistent with their breed history. Analysis of selection signatures using multiple methods (FST, π ratio, Tajima's D), 370 candidate genes were screened in the black wool group (GBB vs GBW); among them, MC1R, MLPH, SPIRE2, RAB17, SMARCA4, IRF4, CAV1, USP7, TP53, MYO6, MITF, MC2R, TET2, NF1, JAK1, GABRR1 genes are mainly associated with melanin synthesis, melanin delivery, and distribution. The enrichment results of the candidate genes identified 35 GO entries and 19 KEGG pathways associated with the formation of the black phenotype. 311 candidate genes were screened in the white wool group (GBW vs GBB); among them, REST, POU2F1, ADCY10, CCNB1, EP300, BRD4, GLI3, and SDHA genes were mainly associated with interfering with the differentiation of neural crest cells into melanocytes, affecting the proliferation of melanocytes, and inhibiting melanin synthesis. 31 GO entries and 22 KEGG pathways were associated with the formation of the white phenotype. Conclusions: This study provides important information for understanding the genetic mechanism of wool color in Gangba, and provides genetic knowledge for improving and optimizing the wool color of Tibetan sheep. Genetic improvement and selective breeding to produce wool of specific colors can meet the demand for a diversity of wool products in the Tibetan wool textile market. [ABSTRACT FROM AUTHOR]

The slow-developing neurological disorder Alzheimer’s disease (AD) has no recognized etiology. A bioinformatics investigation verified copper metabolism indicators for AD development. GEO contributed AD-related datasets GSE1297 and GSE5281. Differential expression analysis and WGCNA confirmed biomarker candidate genes. Each immune cell type in AD and control samples was scored using single sample gene set enrichment analysis. Receiver Operating Characteristic (ROC) analysis, short Time-series Expression Miner (STEM) grouping, and expression analysis between control and AD samples discovered copper metabolism indicators that impacted AD progression. We test clinical samples and cellular function to ensure study correctness. Biomarker-targeting miRNAs and lncRNAs were predicted by starBase. Trust website anticipated biomarker-targeting transcription factors. In the end, Cytoscape constructed the TF/miRNA-mRNA and lncRNA-miRNA networks. The DGIdb database predicted biomarker-targeted drugs. We identified 57 differentially expressed copper metabolism-related genes (DE-CMRGs). Next, fourteen copper metabolism indicators impacting AD progression were identified: CCK, ATP6V1E1, SYT1, LDHA, PAM, HPRT1, SCG5, ATP6V1D, GOT1, NFKBIA, SPHK1, MITF, BRCA1, and CD38. A TF/miRNA-mRNA regulation network was then established with two miRNAs (hsa-miR-34a-5p and 34c-5p), six TFs (NFKB1, RELA, MYC, HIF1A, JUN, and SP1), and four biomarkers. The DGIdb database contained 171 drugs targeting ten copper metabolism-relevant biomarkers (BRCA1, MITF, NFKBIA, CD38, CCK2, HPRT1, SPHK1, LDHA, SCG5, and SYT1). Copper metabolism biomarkers CCK, ATP6V1E1, SYT1, LDHA, PAM, HPRT1, SCG5, ATP6V1D, GOT1, NFKBIA, SPHK1, MITF, BRCA1, and CD38 alter AD progression, laying the groundwork for disease pathophysiology and novel AD diagnostic and treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: The incidence of arterial stenosis is increasing year by year. In order to better diagnose and treat arterial stenosis, numerical simulation technology has become a popular method. OBJECTIVE: A novel model is constructed to investigate the influence of microcirculation on the hemodynamics of artery bypass graft. METHODS: In this paper, a severely narrow artery bypass graft model is considered. The geometric shape includes a narrow artery tube and a bypass graft of the same diameter with a 45° suture angle. The fluid-structure interaction model is considered by finite element numerical calculation, and the flow is simulated with microcirculation as the outlet boundary condition. The changes of blood flow velocity, pressure and wall shear stress are analyzed. RESULTS: The results show that blood almost entirely flows into the graft tube and there is no recirculation area at the anastomosis. CONCLUSION: The artery bypass graft model considering microcirculation function could simulate the physiological characteristics of blood flow more reasonably, and it provide helps for clinicians to diagnose and treat arterial stenosis. [ABSTRACT FROM AUTHOR]

The quality properties and antioxidant activities of tiger nut (Cyperus esculentus L.) oil produced using mechanical expression with subcritical n -butane extraction (ME-SBE) and supercritical CO 2 extraction (ME-SCO 2 E) were investigated and compared with mechanical expression or critical fluid extraction. Results showed that the highest extraction yield was obtained by ME-SBE (28.47 ± 0.20 g/100 g) and ME-SCO 2 E (28.56 ± 0.24 g/100 g). The content of tocopherols, β -carotene and total phenolic compound in oil extracted by ME-SBE (30.69 ± 0.15 mg/100 g, 160.56 ± 7.98 μg/100 g and 28.79 ± 0.34 mg sinapic acid/100 g, respectively) were the highest, and followed by ME-SCO 2 E oil, For fatty acid composition, five oils were similar and rich in oleic acid (73.81–74.10%) and linoleic acid (8.75–8.89%). Furthermore, oil extracted by ME-SBE presented the uppermost antioxidant activities and oxidation stability, which were correlated with α-tocopherols, total tocopherols and total phenolic compound content. Thus, mechanical expression with subcritical n -butane extraction appeared to be preferable for tiger nut oil extraction. • Profiles of tiger nut oils obtained by five methods were studied. • ME-SBE was proven to be the most suitable method, and the highest yield was 28.5 g/100 g • Tiger nut oils showed a predominance of oleic acid (73.81–74.10%). • Oil extracted by ME-SBE appeared better qualities and antioxidant activities. [ABSTRACT FROM AUTHOR]

[Display omitted] • BRS and URS behaviors of HfO x :Cu samples under different conditions were studied. • Better control of filaments led to the uniform switching performance of BRS sample. • Forming processes under different voltage polarities were investigated. • The type and number of defects showed a crucial role on switching behaviors. Dopants-dependent polarity transition of switching behaviors for HfO x :Cu-based RRAM were investigated. By inducing different concentrations of Cu dopants and setting compliance current, the BRS and URS behaviors of HfO x :Cu films were demonstrated. The chemical bonding states and the doping concentrations of HfO x :Cu films were analyzed by XPS technology. The electroforming processes of BRS and URS behaviors under different polarity of applied voltage were explored to understand the different behaviors of HfO x :Cu films. The uniform distribution of resistances and switching voltages, large memory window and good reliability can be observed for BRS sample. While the excess dopants in the film resulted in the poor reliability of URS sample. The different switching behaviors was closely related to the type and number of defects in the film and their migration may show some effect on multi-level behavior. The switching mechanisms of BRS and URS behaviors of HfO x :Cu films were clarified in the view of oxygen vacancies and Cu ions, and the physical models were proposed. [ABSTRACT FROM AUTHOR]

Various congenital and acquired urinary system abnormalities can cause structural damage to patients' bladders. This study aimed to construct and evaluate a novel surgical patch encapsulated with adipose-derived stem cells (ADSCs) for bladder tissue regeneration. The surgical patch consists of multiple biomaterials, including bladder acellular matrix (BAM), collagen type I from rat tail, microparticle emulsion cross-linking polylactic-co-glycolic acid (PLGA)-chitosan (CS) with PLGA-sodium alginate (SA), and growth factors. ADSCs were seeded on the surgical patch. Approximately 50% of the bladder was excised and replaced with a surgical patch. Histological, immunohistochemical and urodynamic analyses were performed at the 2nd, 4th, and 8th weeks after surgery, respectively. The PLGA-CS, PLGA-SA or surgical patch showed no cytotoxicity to ADSCs. PLGA-CS cross-linked with PLGA-SA at a ratio of 5:5 exhibited a loose microporous structure and was chosen as the candidate for ADSC seeding. We conducted bladder repair surgery in rats using the patch, successfully presenting urothelium layers, muscle bundles, and vessel regeneration and replacing 50% of the rat's natural bladder in vivo. Experiments through qualitative and quantitative evaluation demonstrate the application potential of the composite biomaterials in promoting the repair and reconstruction of bladder tissue. [ABSTRACT FROM AUTHOR]

The assumption that the composition of continental input can be characterized from crustal rock types is the prerequisite for the application of the molybdenum (Mo) isotopic composition as an agent to determine variations in the redox state of the paleo-oceans. The Mo isotopes' behavior in the weathered profile of basalt and granite had been studied in pervious works (Pearce et al., 2010, Voegelin et al., 2012 and Wang et al., 2018). However, the Mo isotopes' behavior in the weathered profile of carbonate rock is unknown. In this work, the Mo concentration and Mo isotopic composition in a weathered profile from Guizhou province, China, are investigated for the first time to understand the behavior of Mo isotopes during carbonate rock chemical weathering. The profile is developed on Early Triassic dolomite. According to the field observation and element ratios, the weathered profile is divided into intensely weathered zone (IWZ), weekly weathered zone (WWZ) and fresh bedrock. The clear correlation between Hf and Zr concentration suggests that the dolomite is the parental material for the terra rossa. The τMo of weather soil ranging from ‒1.37 to –0.14 indicates the significant loose of Mo. The δ98Mo of the soil varies from –0.66 to 0.12‰, markedly lighter than the fresh bedrocks (1.82 to 1.97‰). The difference between soils and fresh bedrocks in δ98Mo suggests that Mo isotopes are fractionated during carbonate rock chemical weathering and heavy Mo isotopes are preferentially released, similar to the weathered profile of basalt and granite. According to the coupling relationship between Mo/Al2O3 and δ98Mo, the weathered model of dolomite was established: (1) the carbonate component is firstly dissolved, releasing most Mo with heavy Mo isotope composition. (2) The detrital component then is weathered to form secondary minerals, which adsorb the Mo from weathering fluid. Thus, the Mo/Al2O3 and δ98Mo of samples from IWZ are greater than that of WWZ. [ABSTRACT FROM AUTHOR]

The development of an efficient and convenient material to improve skin tissue regeneration is a major challenge in healthcare. Inspired by the theory of moist wound healing, portable chitooligosaccharide (COS)/sodium alginate (SA) dual-net gel films containing multiple metal ions were prepared by a casting and in-situ spray method, which can be used to significantly promote wound healing without the use of therapeutic drugs. A variety of divalent cations was introduced in this experiment to improve the advantages of each metal ion by forming metal ion chelates with COS. Moreover, the physicochemical properties and antioxidant properties of nIon2+-COS/SA gel films were systematically characterized and evaluated by in vitro experiments. The gel films showed good antibacterial activity against Gram-negative and Gram-positive bacteria. In addition, the gel films showed good cytocompatibility in cellular experiments, and the gel films with Zn2+ and Sr2+ addition significantly accelerated wound healing in whole skin defect model experiments. Therefore, this nIon2+-COS/SA gel film is an ideal candidate material for wound dressing. [ABSTRACT FROM AUTHOR]

• A polysaccharide (MPW) was isolated from Lepidium meyenii Walp. (Maca). • MPW is mainly composed of →4) -α-D-Glcp- (1 → glycoside bond. • MPW showed significant in vivo tumor immunotherapy activity. • MPW and its cationic derivative (C-MPW) can re-direct TAMs to M1 phenotype. • C-MPW exhibited a stronger tumor immunotherapy activity than MPW. In the current study, we developed a synergistic chemo-immunotherapy using doxorubicin (Dox) and a natural polysaccharide as immunomodulator. First, we isolated a polysaccharide (MPW) from the root of Lepidium meyenii Walp. (maca) and characterized its chemical properties. MPW contains → 4) -α-D-Glcp- (1 → glycosidic bonds, while the terminal α-D-Glcp- (1 → group is connected to the main chain through an O -6 bond. This polysaccharide was then modified by cationization (C-MPW) to enhance immunoregulatory activity. MPW and C-MPW were combined with Dox and their chemo-immunotherapy effects on 4T1 tumor-bearing mice were assessed. Results indicated that the combination of MPW/C-MPW exerted a stronger anti-tumor effect than Dox alone, while reducing systemic toxicity and inhibiting tumor metastasis. In addition, MPW and C-MPW exerted tumor immunotherapy effects through the NF-κB, STAT1, and STAT3 signaling pathways, redirecting TAMs to the M1 phenotype that facilitates immunological responses against tumors. As a result, the immunosuppressive tumor microenvironment was remodeled into an immune-activated state due to enhanced secretion of IL-12, TNF-α, and INF-γ. Moreover, C-MPW exerted a stronger immunomodulatory effect than MPW. In conclusion, MPW and its cationic derivative are promising tools for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

• Nine undescribed sesquiterpene coumarins were isolated from F. sinkiangensis. • Compound 5 was isolated from F. sinkiangensis as natural SC for the first time. • The anti-neuroinflammatory effects of the identified SCs were evaluated in vitro. • SCs may be potential neuroinflammatory inhibitors. Nine undescribed (1 – 4 , 6 – 10) sesquiterpene coumarins, together with a new natural one (5) and ten known ones (11 – 20), were isolated from the low polarity fraction of the 95% ethanol extract of the resin of Ferula sinkiangensis. Their structures were elucidated based on the comprehensive analysis of HRESIMS, 1D and 2D NMR data. The absolute configurations were determined by comparison of experimental and calculated ECD spectra. All the identified SCs were evaluated for their anti-neuroinflammatory activities in LPS-induced BV-2 cells. Ferusingensine G (8) displayed a significant inhibitory effect on nitric oxide (NO) production with an IC 50 value of 1.2 μM. The results suggested that natural SCs might be served as potential neuroinflammatory inhibitors. [ABSTRACT FROM AUTHOR]

• Zinc-phthalocyanine with a new phase (η-phase) has been fabricated. • The crystal structure and optical properties of zinc-phthalocyanine have been investigated. • The crystal-structure parameters of the new prepared Zinc-phthalocyanine were obtained by fitting the X-ray diffraction data. Zinc-phthalocyanine has great potential for the applications in band-structure engineering, organic solar cells and photodynamic therapy. The optical and structural properties of zinc-phthalocyanine have been studied extensively previously. Here we report we have fabricated the nanowires of zinc-phthalocyanines (the η -phase) and investigated their crystal structures and optical properties. The in-situ x-ray-diffraction experiments show that zinc-phthalocyanine nanowires grown at the low-temperature region have a distinct crystal structure as compared with the zinc-phthalocyanine polymorphs reported previously. We have also fitted the x-ray diffraction data and obtained the crystal-structure parameters, which further suggests that the nanowire phase has a new crystal structure. The UV–Vis experiments suggest similar qualitative feature in both the Q-band and the B-band, but slightly different quantitative perspectives. As explained by using the first-principles calculations, a mixture of intra-molecular and charge-transfer excitations can account for the splitting of the Q-band. Our work can provide a solid foundation for the further applications of zinc-phthalocyanines in organic optoelectronics. [ABSTRACT FROM AUTHOR]

• A LV quantification method that provide both the quantification results and the sample-level confidence assessment. • An uncertainty-weighted loss to attenuate the effect of difficult samples and improve the quantification performance. • Two types of uncertainties in the quantification model are investigated and reveal weak correlation with quantification error. Quantification of cardiac left ventricle has become a hot topic due to its great significance in clinical practice. Many efforts have been devoted to LV quantification and obtained promising performance with the help of various deep neural networks when validated on a group of samples. However, none of them can provide sample-level confidence of the results, i.e., how reliable is the prediction result for one single sample, which would help clinicians make decisions of whether or not to accept the automatic results. In this paper, we achieve this by introducing the uncertainty analysis theory into our LV quantification network. Two types of uncertainty, Model Uncertainty, and Data Uncertainty are analyzed for the quantification performance and contribute to the sample-level confidence. Experiments with data of 145 subjects validate that our method not only improved the quantification performance with an uncertainty-weighted regression loss but also is capable of providing for each sample the confidence level of the estimation results for clinicians' further consideration. [ABSTRACT FROM AUTHOR]