Search

Bovine tuberculosis (bTB) caused by Mycobacterium bovis (M. bovis) represents one of major zoonotic diseases among cattle, it also affects the health of human, other domestic animals and wild life populations. Inhalation of infected aerosol droplets is considered as the most frequent route of the infection. This study aims to investigate the current forms of tuberculosis in cattle and identify the possible transmission modes in dairy farms of China. 13,345 cows from eight dairy farms in three provinces were comprehensively diagnosed by a multitude of assays, including SIT, CIT, IFN-γ assay and ELISA. It has been indicated that advanced infection of bTB was found in 752 (5.64%) cattle, suggesting a high prevalence of tuberculosis in these dairy farms. In the necropsy examination of 151 positive cattle, typical bTB lesions were observed in 131 cattle (86.75%), of which, notably, 90.84% lesions appeared in liver, spleen, mesenteric lymph nodes, mammary lymph nodes and other organs, taking up a large proportion among cattle with advanced bTB infection. 71.26% extrapulmonary tuberculosis (EPTB) was related to gastrointestinal system. M. bovis nucleic acid was further found in milk and feces samples and M. bovis was even isolated from milk samples. Phylogenetic analysis based on whole genome sequencing unraveled that six isolates were closely related to M. bovis AF2122/97 originated from UK, whereas four isolates shared close relation to M. bovis 30 from China, respectively. Our data demonstrate that the increase of EPTB transmitted by digestive tract is implicated in the current high prevalence rate of bTB in China, which also provides leads for bTB control in other countries with high prevalence of bTB in the future.

Objective. To investigate the differences of candidate cerebrospinal fluid (CSF) biomarkers associated with multiple system atrophy (MSA) and Parkinson’s disease (PD). Method. Here, a systematic review and meta-analysis were conducted on studies related to CSF biomarkers associated with MSA and PD obtained from PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled where appropriate and used to calculate standardized mean differences (SMDs) with 95% confidence intervals (CI). Heterogeneity was assessed using the I2 statistic while Egger’s test was used to test for existing publication bias. Results. MSA patients had higher CSF t-tau (SMD=0.41, 95% CI: 0.10 to 0.72) and YKL-40 (SMD=0.63, 95% CI 0.12 to1.15) as well as DJ-1 (SMD=1.05, 95% CI 0.67 to 1.42) levels than PD patients, while CSF p-tau (SMD=−0.17, 95% CI, -0.31 to -0.02) and Aβ-42 (SMD=−0.33, 95% CI, -0.55 to -0.12) levels in MSA patients were lower than those in PD patients. There were no differences in CSF’s GFAP and Flt3 ligand levels in both MSA and PD patients. Conclusion. The study revealed the differences in CSF biomarker levels between MSA and PD cohorts that can be further explored to clinically distinguish MSA from PD.

Objectives. Inflammatory disease characterized by clinical destructive respiratory disorder is called acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Studies have shown that luteolin exerts anti-inflammatory effects by increasing regulatory T cells (Tregs). In this study, we aimed to determine the effects of luteolin on ALI/ARDS and Treg differentiation. Methods. In this paper, we used cecal ligation puncture (CLP) to generate an ALI mouse model to determine the effects of luteolin on ALI/ARDS. Lung tissues were stained for interleukin- (IL-) 17A and myeloperoxidase (MPO) by immunohistochemical analysis. The levels of Treg-related cytokines in serum and bronchoalveolar lavage fluid (BALF) of mice were detected. The protein levels of NF-κB p65 in lung tissues were measured. Macrophage phenotypes in lung tissues were measured using immunofluorescence. The proportion of Tregs in splenic mononuclear cells and peripheral blood mononuclear cells (PBMCs) was quantified. Furthermore, in vitro, we evaluated the effects of luteolin on Treg differentiation, and the effects of IL-10 immune regulation on macrophage polarization were examined. Results. Luteolin alleviated lung injury and suppressed uncontrolled inflammation and downregulated IL-17A, MPO, and NF-κB in the lungs of CLP-induced mouse models. At this time, luteolin upregulated the level of IL-10 in serum and BALF and the frequency of CD4+CD25+FOXP3+ Tregs in PBMCs and splenic mononuclear cells of CLP mice. Luteolin treatment decreased the proportion of M1 macrophages and increased the proportion of M2 macrophages in lungs of CLP-induced mouse models. In vitro, administration of luteolin significantly induced Treg differentiation, and IL-10 promoted the polarization of M2 macrophages but reduced the polarization of M1 macrophages. Conclusions. Luteolin alleviated lung injury and suppressed uncontrolled inflammation by inducing the differentiation of CD4+CD25+FOXP3+ Tregs and upregulating the expression of IL-10. Furthermore, the anti-inflammatory cytokine IL-10 promoted polarization of M2 macrophages in vitro. Luteolin-induced Treg differentiation from naïve CD4+ T cells may be a potential mechanism for regulating IL-10 production.

Purpose. Aspergillus fumigatus, as an opportunistic fungus, has developed a series of escape mechanisms under the host’s immune response to obtain nutrients and promote fungal growth in the hostile environment. The immune escape of pathogens may be through suppressing the inflammatory response mediated by regulatory T cells (Tregs). The aim of this study was to explore whether A. fumigatus influences Gasdermin-D-dependent pyroptosis of the lung by regulating Toll-like receptor 2-mediated regulatory T cell differentiation. Methods. Collect peripheral blood from patients with A. fumigatus. ELISA kits we used to detect the expression levels of IL-1β, IL-6, IL-2R, and IL-10 in the serum and flow cytometry to detect the percentage of CD4+CD25+Foxp3+ Tregs in the patients’ peripheral blood mononuclear cells (PBMCs). The mouse model of A. fumigatus infection was constructed by tracheal instillation. The pathological changes in the lungs of the mice were observed under a microscope. The fungal load in the lung tissue was determined by the plate colony count. ELISA kit was used to detect the lung tissue homogenate proinflammatory cytokines TNF-α, IL-6, CCL2, and VEGF. Q-PCR was used for the detection of the expression of Foxp3 and TLR2 genes in the lung. Western blot was used for the detection of the expression of TLR2, Gasdermin-D (GSDMD), IL-1α, and IL-1β in the lung. Flow cytometry was used to detect splenic CD4+CD25+FOXP3+ Tregs. Using magnetic beads to extract CD4+ T cells from mice spleen, the effects of A. fumigatus conidia or TLR2 inhibitor (C29) to differentiate CD4+ T cells in vitro were tested. Results. The expression of Foxp3 and TLR2 in the lung tissue of mice infected with A. fumigatus increased, and we observed that the proportion of Tregs in both A. fumigatus infection patients and mice was upregulated. After using the CD25 neutralizing antibody, the number of Tregs in the mice spleen was significantly reduced. However, lung damage was reduced and the ability to clear lung fungi was enhanced. We found that the Tregs in TLR2−/− mice were significantly reduced and the nonlethal dose of A. fumigatus conidia did not cause severe lung damage in TLR2−/− mice. Compared with that of wild-type mice, the fungal burden in the lung of TLR2-deficient mice was reduced and the knockout of TLR2 changed the expression of GSDMD, IL-1α, and IL-1β in A. fumigatus. In in vitro experiments, we found that the inhibition of TLR2 can reduce Treg differentiation. Conclusions. A. fumigatus triggers CD4+CD25+FOXP3+ Treg proliferation and differentiation by activating the TLR2 pathway, which may be a potential mechanism for evading host defenses in A. fumigatus. This effect can modulate GSDMD-dependent pyroptosis and may partly involve TRL2 signaling.

Nonalcoholic steatohepatitis (NASH), the progressive form of nonalcoholic fatty liver disease (NAFLD), is becoming a common chronic liver disease with the characteristics of steatosis, inflammation and fibrosis. Macrophage plays an important role in the development of NASH. In this study, Annexin A5 (Anx A5) is identified with the special effect on hepatic macrophage phenotype shift from M1 to M2. And it is further demonstrated that Anx A5 significantly switches metabolic reprogramming from glycolysis to oxidative phosphorylation in activated macrophages. Mechanistically, the main target of Anx A5 in energy metabolism is confirmed to be pyruvate kinase M2 (PKM2). And we following reveal that Anx A5 directly interacts with PKM2 at ASP101, LEU104 and ARG106, inhibits phosphorylation of Y105, and promotes PKM2 tetramer formation. In addition, based on the results of PKM2 inhibitor (compound 3k) and the phosphorylated mutation (PKM2 (Y105E)), it is proved that Anx A5 exhibits the function in macrophage polarization dependently on PKM2 activity. In vivo studies also show that Anx A5 improves steatosis, inflammation and fibrosis in NASH mice due to specially regulating hepatic macrophages via interaction with PKM2. Therefore, we have revealed a novel function of Anx A5 in hepatic macrophage polarization and HFD-induced NASH, providing important insights into the metabolic reprogramming, which is important for NASH therapy.

Lysine acetylation is a vital post-translational modification (PTM) of proteins, which plays an important role in cancer development. In healthy human liver tissues, multiple non-histone proteins were identified with acetylation modification, however, the role of acetylated proteins in hepatocellular carcinoma (HCC) development remains largely unknown. Here we performed a quantitative acetylome study of tumor and normal liver tissues from HCC patients. Overall, 598 lysine acetylation sites in 325 proteins were quantified, and almost 59% of their acetylation levels were significantly changed. The differentially acetylated proteins mainly consisted of non-histone proteins located in mitochondria and cytoplasm, which accounted for 42% and 24%, respectively. Bioinformatics analysis showed that differentially acetylated proteins were enriched in metabolism, oxidative stress, and signal transduction processes. In tumor tissues, 278 lysine sites in 189 proteins showed decreased acetylation levels, which occupied 98% of differentially acetylated proteins. Moreover, we collected twenty pairs of tumor and normal liver tissues from HCC male patients, and found that expression levels of SIRT1 (p = 0.002), SIRT2 (p = 0.01), and SIRT4 (p = 0.045) were significantly up-regulated in tumor tissues. Over-expression of possibly accounted for the widespread deacetylation of non-histone proteins identified in HCC tumor tissues, which could serve as promising predictors of HCC. Taken together, our work illustrates abundant differentially acetylated proteins in HCC tumor tissues, and offered insights into the role of lysine acetylation in HCC development. It provided potential biomarker and drug target candidates for clinical HCC diagnosis and treatment.

Aircraft detection in remote sensing images (RSIs) has drawn widespread attention in recent years, which has been widely used in the military and civilian fields. While the complex background, variations of aircraft pose and size bring great difficulties to the effective detection. In this paper, we propose a novel aircraft target detection scheme based on small training samples. The scheme is coarse-to-fine, which consists of two main stages: region proposal and target identification. First, in the region proposal stage, a circular intensity filter, which is designed based on the characteristics of the aircraft target, can quickly locate the centers of multi-scale suspicious aircraft targets in the RSIs pyramid. Then the target regions can be extracted by adding bounding boxes. This step can get high-quality but few candidate regions. Second, in the stage of target identification, we proposed a novel rotation-invariant feature, which combines rotation-invariant histogram of oriented gradient and vector of locally aggregated descriptors (VLAD). The feature can characterize the aircraft target well by avoiding the impact of its rotation and can be effectively used to remove false alarms. Experiments are conducted on Remote Sensing Object Detection (RSOD) dataset to compare the proposed method with other advanced methods. The results show that the proposed method can quickly and accurately detect aircraft targets in RSIs and achieve a better performance.

In order to improve the geo-location accuracy of the airborne optoelectronic platform and eliminate the influence of assembly systematic error on the accuracy, a systematic geo-location error correction method is proposed. First, based on the kinematic characteristics of the airborne optoelectronic platform, the geo-location model was established. Then, the error items that affect the geo-location accuracy were analyzed. The installation error between the platform and the POS was considered, and the installation error of platform’s pitch and azimuth was introduced. After ignoring higher-order infinitesimals, the least square form of systematic error is obtained. Therefore, the systematic error can be obtained through a series of measurements. Both Monte Carlo simulation analysis and in-flight experiment results show that this method can effectively obtain the systematic error. Through correction, the root-mean-square value of the geo-location error have reduced from 45.65 m to 12.62 m, and the mean error from 16.60 m to 1.24 m. This method can be widely used in systematic error correction of relevant photoelectric equipment.

Correlation filter (CF) based trackers have gained significant attention in the field of visual single-object tracking, owing to their favorable performance and high efficiency; however, existing trackers still suffer from model drift caused by boundary effects and filter degradation. In visual tracking, long-term occlusion and large appearance variations easily cause model degradation. To remedy these drawbacks, we propose a sparse adaptive spatial-temporal context-aware method that effectively avoids model drift. Specifically, a global context is explicitly incorporated into the correlation filter to mitigate boundary effects. Subsequently, an adaptive temporal regularization constraint is adopted in the filter training stage to avoid model degradation. Meanwhile, a sparse response constraint is introduced to reduce the risk of further model drift. Furthermore, we apply the alternating direction multiplier method (ADMM) to derive a closed-solution of the object function with a low computational cost. In addition, an updating scheme based on the APCE-pool and Peak-pool is proposed to reveal the tracking condition and ensure updates of the target’s appearance model with high-confidence. The Kalam filter is adopted to track the target when the appearance model is persistently unreliable and abnormality occurs. Finally, extensive experimental results on OTB-2013, OTB-2015 and VOT2018 datasets show that our proposed tracker performs favorably against several state-of-the-art trackers.

Background: Selecting patients who potentially benefit from immune checkpoint inhibitors (ICIs) is critical. Programmed death ligand-1 (PD-L1) protein immunohistochemical expression on cancer cells or immune cells and next-generation sequencing-based tumor mutational burden (TMB) are hot spots in studies on ICIs, but there is still confusion in the testing methods. Because blood samples are much easier for clinical application, many potential peripheral biomarkers have been proposed. This study identified blood parameters associated with the outcome of non-small cell lung cancer (NSCLC) patients with ICI monotherapy.Materials and Methods: Data from 76 NSCLC patients were analyzed retrospectively. To assess the connection between survival and peripheral blood markers measured before the first and fifth doses of ICI treatment, we utilized Cox regression model survival analysis and receiver operating characteristic (ROC) curve analysis to assess the markers.Results: In the nivolumab cohort, the optimal cutoffs for predicting 11-month overall survival (OS) were 168.13 and 43 g/L for platelet-to-lymphocyte ratio (PLR) and albumin, respectively. When patients were grouped with PLR and albumin, a significant difference in SD-PR vs. PD rate was found between the high and low groups, which was not found when the patients were grouped by PD-L1 expression. Patients with high PLR (>168.13) or low albumin ( ≤ 43 g/L) before ICI had a significantly increased hazard of progression, separately (for PLR, P = 0.006; for albumin, P = 0.033), and of death (for PLR, P = 0.014; for albumin, P = 0.009) compared with those patients who had low PLR or albumin levels. More importantly, we found that a higher PLR (>168.13) before the fifth dose of ICIs was also a prognostic biomarker, which significantly correlated with shorter OS in both the nivolumab (P = 0.046) and durvalumab cohorts (P = 0.028).Conclusions: PLR and albumin may help in the stratification of high progression and death risk groups in advanced NSCLC patients treated with nivolumab and durvalumab monotherapy.

Objectives: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Curcumin has been reported to be an anti-inflammatory factor through enhancing the function of regulatory T cells (Tregs). This study aimed to explore the effect of curcumin on the differentiation of Tregs and the role of curcumin in ALI/ARDS. Methods: A cecal ligation and puncture (CLP)-induced acute lung injury mouse model was used to explore the effect of curcumin in ALI/ARDS. The severity of lung injury was evaluated. Immunohistochemistry of IL-17A and MPO in lung tissue was examined. Treg-related cytokine levels in serum and bronchoalveolar lavage fluid (BALF) were tested. The expression of nuclear factor-kappa B (NF-κB) in lung tissue was detected. Macrophages in lung tissue were detected by immunofluorescence. Splenic CD4+CD25+FOXP3+ Tregs were quantified, and the differentiation of Tregs from naïve CD4 + T cell and STAT5 was evaluated. The expression of IL-10 during naïve CD4 + T cell differentiation in vitro was tested. Results: Curcumin alleviated lung injury in the induced CLP mouse model and suppressed inflammation. IL-17A, MPO-producing neutrophils, and NF-κB p65 expression in lungs of CLP mice decreased significantly after pretreatment with curcumin. We found curcumin could regulate M1/M2 macrophage levels in lungs of CLP mice. This may have been through regulating the differentiation of Tregs and the production of Treg-derived IL-10. Treg-derived IL-10 is the main factor that could affect macrophage polarization. We found curcumin could increase Treg proportions in vivo and up-regulate IL-10 expression in serum and BALF of CLP mice. In our in vitro experiments, we found curcumin could promote Treg differentiation and increase the production of IL-10. Conclusions: Curcumin can reduce the degree of severity of ALI and uncontrolled inflammation through promoting the differentiation of naïve CD4 + T cells to CD4+ CD25+ FOXP3+ Tregs. Curcumin promotes the conversion of macrophages from M1 to M2. The differentiation of Tregs induced by curcumin may be one source of IL-10 immune modulation.

Human umbilical-cord mesenchymal stem cells (hUCMSCs) are a safe and convenient source of MSCs and have shown beneficial effects in neonatal infection and sepsis animal models. However, the factors leading to improved outcomes are still unclear. The aim of this study was to investigate the antibacterial effect and regulation of antimicrobial resistance of hUCMSCs. We separated imipenem-resistant Pseudomonas aeruginosa (PA) from neonates and incubated it with hUCMSCs as well as their culture medium. Assessment of direct inhibition of bacterial growth was done by counting CFUs. The concentration of antibacterial peptides in the culture medium of hUCMSCs was measured. Standard PA was inoculated with a sub-inhibitory concentration of imipenem with and without hUCMSC conditioned medium and antimicrobial peptides. The sensitivity to imipenem was detected until PA showed resistance to imipenem. Outer membrane protein (OprD2) mRNA expression in PA before and after the induction of imipenem resistance was analysed. We found that HUCMSCs possessed direct antimicrobial properties against bacteria and could alleviate antibiotic resistance via reserving OprD2 expression in PA.

GZD824 is a novel third-generation BCR-ABL inhibitor. It entered Phase II clinical trials in China and Phase Ib clinical trials in USA in 2019 for treatment of patients with resistant chronic myeloid leukemia (CML). We found that at concentrations below 10 nM, GZD824 significantly suppresses FLT3, FGFR1 and PDGFRα kinase activities and inhibits their signal pathways in MV4-11Flt3-ITD, KG-1FGFR1OP2-FGFR1 and EOL-1FIP1L1-PDGFRa leukemia cells. It selectively inhibits the growth of MV4-11Flt3-ITD, KG-1FGFR1OP2-FGFR1 and EOL-1FIP1L1-PDGFRa cells, and also effectively suppresses the growth of Ba/F3-FLT3-ITD cells harboring F691I and other mutations with IC50 values

A new electrochromic device (ECD) was fabricated, consisting of poly(3,4-(2,2-dimethyl-propylenedioxy)thiophene) (PProDOT–Me2) and tungsten trioxide (WO3) films. The conventional cathodic EC material PProDOT–Me2 acts as an electrocatalytic counter electrode here, working with an electrolyte which contains the Br−/Br3− redox couple to accelerate the electrochromic process and lower the driving voltage of the ECD. The device can be fully colored at under −1.0 V and self-bleached at 0 V (in a short-circuited state) with high optical modulation of 72.4% at 680 nm. Compared with other self-bleaching devices, the response time of 5.6 s for coloring and 15.3 s for bleaching suggests an exceptional switching speed. Additionally, the coloration efficiency (CE) of the device reaches 88.9 cm2/C. When the long-term stability of the device was evaluated, no apparent deterioration was observed after 5000 cycles. Keywords: Electrocatalytic, PProDOT-Me2, Br−/Br3− redox couple, Electrochromic device

BackgroundIt is unclear whether there are individual differences in the long-term efficacy of computer-assisted and traditional total knee arthroplasty. The purpose of this study was to perform a meta-analysis comparing the same individuals undergoing computer-assisted and traditional total knee arthroplasty separately to determine whether computer-assisted total knee arthroplasty can provide better lower extremity radiographic results and clinical outcomes.MethodsWe searched literatures to identify relevant randomized controlled trials comparing the effects of computer-assisted and traditional methods in bilateral total knee arthroplasty. After screening, quality evaluation and data extraction according to inclusion and exclusion criteria, the quality and bias risks of the included studies were evaluated. The meta-analysis compared the radiographic results, functional outcomes and complications of the two techniques.ResultsSix clinical controlled trials were included, with total of 1098 patients. The meta-analysis showed that the accuracy in terms of the mechanical axis of the lower extremity, the sagittal alignment of the femoral component and the coronal alignment of the tibial component in computer-assisted total knee arthroplasty was significantly better than those in traditional total knee arthroplasty. There were no differences in the functional results, revision rates or aseptic loosening rates between the two techniques.ConclusionAfter excluding individual differences such as bone development and bone quality, although computer-assisted techniques can better accurately correct the mechanical axis of the lower extremity and the position of prosthesis implantation than traditional techniques, there is no significant difference in the functional results and revision rate of bilateral total knee arthroplasty in the same individual.

Construction of a reliable stock portfolio remains an open issue in quantitative investment. Multiple machine learning models have been trained for stock portfolio selection, but their practical applicability remains limited due to the challenges posed by the characteristic of a low signal-to-noise ratio (SNR), the nature of time-series data, and non-independent identical distribution in financial data. Here, we transformed the stock selection task into a matching problem between a group of stocks and a stock selection target. We proposed a novel representation algorithm of stock selection target and a novel deep matching algorithm (TS-Deep-LtM). Then we proposed a deep stock profiling method to extract the optimal feature combination and trained a deep matching model based on TS-Deep-LtM algorithm for stock portfolio selection. Especially, TS-Deep-LtM algorithm was obtained by setting statistical indicators to filter and integrate three deep text matching algorithms. This parallel framework design made it good at capturing signals from time-series data and adapting to non-independent identically distributed data. Finally, we applied the proposed model to stock selection and tested long-only portfolio strategies from 2010 to 2017. We demonstrated that the risk-adjusted returns obtained by our portfolio strategies outperformed those obtained by the CSI300 index and learning-to-rank approaches during the same period.

Isoliquiritigenin (ISL) is a flavonoid isolated mainly from the licorice plant, a traditional Chinese herb. ISL has shown anticancer, anti-inflammatory, antioxidant, and antidiabetic activities. However, the pharmaceutical effects of ISL on atherosclerosis are seldom explored. In this study, we used apolipoprotein E (ApoE) knockout mouse model and angiotensin II- (Ang II-) stimulated vascular smooth muscle cells (VSMCs) to elucidate the pharmacological mechanism of ISL to inhibit atherosclerosis. We found that in ApoE−/− mice ISL could attenuate atherosclerotic lesion, reduce serum lipid levels, and inhibit TRPC5 expression. In vitro, ISL inhibited Ang II-stimulated proliferation of VSMCs and suppressed Ang II-induced TRPC5 and PCNA expressions in a dose-dependent fashion. In conclusion, our findings provide novel insight into the pharmacological effects of ISL on atherosclerosis and suggest that ISL is beneficial for cardiovascular protection.

Progranulin (PGRN), which plays an anti-inflammatory role in acute lung injury (ALI), is promising as a potential drug. Studies have shown that regulatory T cells (Tregs) and interleukin- (IL-) 10 can repress inflammation and alleviate tissue damage during ALI. In this study, we built a lipopolysaccharide- (LPS-) induced ALI mouse model to illustrate the effect of PGRN on regulation of Treg differentiation and modulation of IL-10 promoting macrophage polarization. We found that the proportion of Tregs in splenic mononuclear cells and peripheral blood mononuclear cells was higher after treatment with PGRN. The increased proportion of Tregs after PGRN intratracheal instillation was consistent with the decreased severity of lung injury, the reduction of proinflammatory cytokines, and the increase of anti-inflammatory cytokines. In vitro, the percentages of CD4+CD25+FOXP3+ Tregs from splenic naïve CD4+ T cells increased after PGRN treatment. In further research, it was found that PGRN can regulate the anti-inflammatory factor IL-10 and affect the polarization of M1/M2 macrophages by upregulating IL-10. These findings show that PGRN likely plays a protective role in ALI by promoting Treg differentiation and activating IL-10 immunomodulation.

This paper focuses on system reliability analysis with dependent competing failure process due to soft failure and hard failure. Some new probabilistic methods based on cumulative shock model and nonlinear Wiener process under different shifting thresholds situation are obtained. Considering that nonlinearity exists extensively in practice, the continuous soft failure process is governed by random effected nonlinear Wiener process. Firstly, reliability evaluation models for hard failure and soft failure are obtained under the cumulative shock, respectively. Furthermore, some system reliability models under different shifting thresholds situation are studied, in which failure threshold will decrease after a certain number of shocks. A real numerical example about fatigue crack growth dataset is carried out to demonstrate the proposed procedure. Numerical results indicate that both random shocks and shifting threshold have significant effect on system reliability. Finally, some sensitivity analysis are also been given.

Glycyrrhiza uralensis Fisch. is used in large quantities in traditional Chinese medicine. It contains flavonoids, saponins, and polysaccharides, with flavonoids being the main active ingredients. In this study, flavonoids were isolated from the roots of Glycyrrhiza uralensis Fisch. grown in 21 areas in China by water extraction, alcohol precipitation, polyamide resin separation, and other methods. Fingerprints were established by high performance liquid chromatography (HPLC). There were 15 common peaks in the fingerprints by similarity evaluations of the chromatographic fingerprints. The spectrum-effect relationships between the HPLC fingerprints and pharmacological activities of flavonoids in G. uralensis Fisch., including the heat clearing, detoxifying effects, cough relief, and phlegm elimination effects, were assessed by gray relational analysis and partial least squares regression. After HPLC-quadrupole time-of-flight mass spectrometry and standard comparison, these five identified compounds (liquiritin apioside, neoisoliquiritin, licochalcone A, licochalcone B, and licochalcone C) could be used to evaluate licorice quality with regard to its efficacy. This research provides a scientific basis for improving licorice quality and also establishes a model for modernization of traditional Chinese medicines.

Angiogenesis is a crucial event during cancer progression that regulates tumor growth and metastasis. Activin receptor-like kinase 1 (ALK1), predominantly expressed in endothelial cells, plays a key role in the organization of neo-angiogenic vessels. Therapeutic targeting of ALK1 has been proposed as a promising strategy for cancer treatment, and microRNAs (miRNAs) are increasingly being explored as modulators of angiogenesis. However, the regulation of ALK1 by miRNAs is unclear. In this study, we identified that ALK1 is directly targeted by miR-199b-5p, which was able to inhibit angiogenesis in vitro and in vivo. Moreover, it was found that miR-199b-5p was repressed in breast cancer cells and its expression was decreased during the VEGF-induced angiogenesis process of human umbilical vein endothelial cells (HUVECs). Overexpression of miR-199b-5p inhibited the formation of capillary-like tubular structures and migration of HUVECs. Furthermore, overexpression of miR-199b-5p inhibited the mRNA and protein expression of ALK1 in HUVECs by directly binding to its 3’UTR. Additionally, overexpression of miR-199b-5p attenuated the induction of ALK1/Smad/Id1 pathway by BMP9 in HUVECs. Finally, overexpression of miR-199b-5p reduced tumor growth and angiogenesis in in vivo. Taken together, these findings demonstrate the anti-angiogenic role of miR-199b-5p, which directly targets ALK1, suggesting that miR-199b-5p might be a potential anti-angiogenic target for cancer therapy.

The current report devised a novel isothermal diagnostic assay, termed as nanoparticle-based biosensor (NB)- and antarctic thermal sensitive uracil-DNA-glycosylase (ATSU)-supplemented polymerase spiral reaction (PSR; NB-ATSU-PSR). The technique merges enzymatic digestion of carryover contaminants and isothermal nucleic acid amplification technique (PSR) for simultaneous detection of nucleic acid sequences and elimination of carryover contamination. In particular, nucleic acid amplification and elimination of carryover contamination are conducted in a single pot and, thus, the use of a closed-tube reaction can remove undesired results due to carryover contamination. For demonstration purpose, Klebsiella pneumoniae is employed as the model to demonstrate the usability of NB-ATSU-PSR assay. The assay's sensitivity, specificity, and practical feasibility were successfully evaluated using the pure cultures and sputum samples. The amplification products were detectable from as little as 100 fg of genomic DNAs and from ~550 colony-forming unit (CFU) in 1 ml of spiked sputum samples. All K. pneumoniae strains examined were positive for NB-ATSU-PSR detection, and all non-K. pneumoniae strains tested were negative for the NB-ATSU-PSR technique. The whole process, including rapid template preparation (20 min), PSR amplification (60 min), ATSU treatment (5 min), and result reporting (within 2 min), can be finished within 90 min. As a proof-of-concept methodology, NB-ATSU-PSR technique can be reconfigured to detect various target nucleic acid sequences by redesigning the PSR primer set.

This paper proposes a computer-aided Dynamic Visual Research and Design Protocol for environmental designers to analyze humans’ dynamic visual experiences in the city and to simulate dynamic vision in the design process. The Protocol recommends using action cameras to collect massive dynamic visual data from participants’ first-person perspectives. It prescribes a computer-aided visual analysis approach to produce cinematic charts and storyboards, which further afford qualitative interpretations for aesthetic assessment and discussion. Employing real-time 3D simulation technologies, the Protocol enables the simulation of people’s dynamic vision in designed urban environments to support evaluation in design. Detailed contents and merits of the Protocol were demonstrated by its application in the Urbanscape Studio, a community participatory design course based at Watertown, South Dakota.

Background: Array comparative genomic hybridization (aCGH), karyotyping and fluorescence in situ hybridization (FISH) analyses have been used in a clinical cytogenetic laboratory. A systematic analysis on diagnostic findings of cytogenomic abnormalities in current prenatal and pediatric settings provides approaches for future improvement.Methods: A retrospective analysis was performed on abnormal findings by aCGH, karyotyping, and FISH from 3,608 prenatal cases and 4,509 pediatric cases during 2008–2017. The diagnostic accuracy was evaluated by comparing the abnormality detection rate (ADR) and the relative frequency (RF) of different types of cytogenomic abnormalities between prenatal and pediatric cases. A linear regression correlation between known prevalence and ADR of genomic disorders was used to extrapolate the prevalence of other genomic disorders. The diagnostic efficacy was estimated as percentage of detected abnormal cases by expected abnormal cases from served population.Results: The composite ADR for numerical chromosome abnormalities, structural chromosome abnormalities, recurrent genomic disorders, and sporadic pathogenic copy number variants (pCNVs) in prenatal cases were 13.03%, 1.77%, 1.69%, and 0.9%, respectively, and were 5.13%, 2.84%, 7.08%, and 2.69% in pediatric cases, respectively. The chromosomal abnormalities detected in prenatal cases (14.80%) were significantly higher than that of pediatric cases (7.97%) (p < 0.05), while the pCNVs detected in prenatal cases (2.59%) were significantly lower than that of pediatric cases (9.77%) (p < 0.05). The prevalence of recurrent genomic disorders and total pCNVs was estimated to be 1/396 and 1/291, respectively. Approximately, 29% and 35% of cytogenomic abnormalities expected from the population served were detected in current prenatal and pediatric diagnostic practice, respectively.Conclusion: For chromosomal abnormalities, effective detection of Down syndrome (DS) and Turner syndrome (TS) and under detection of sex chromosome numerical abnormalities in both prenatal and pediatric cases were noted. For pCNVs, under detection of pCNVs in prenatal cases and effective detection of DiGeorge syndrome (DGS) and variable efficacy in detecting other pCNVs in pediatric cases were noted. Extend aCGH analysis to more prenatal cases with fetal ultrasonographic anomalies, enhanced non-invasive prenatal (NIPT) testing screening for syndromic genomic disorders, and better clinical indications for pCNVs are approaches that could improve diagnostic yield of cytogenomic abnormalities.

The deformation behavior, microstructure evolution and precipitation phase of 617B alloy were studied by Gleeble thermal simulator, SEM and creep rupture test method. The results show that, 617B alloy has a high deformation resistance and the temperature range of processing secure channel is between 1165-1200℃; alloy instability exists in two forms:one is the formation of adiabatic shear band; another is the abnormal growth of full dynamic recrystallization grain; with extension of the stress rupture time, the microhardness increases rapidly and then tends to be steady, γ' is the main precipitate and the precipitate phase grows up with the time extension, but no harmful phases, and with higher stress rupture strength performance.

Abstract Recent interest in high-throughput recording of neuronal activity has motivated rapid improvements in genetically encoded calcium or voltage indicators (GECIs or GEVIs) for all-optical electrophysiology. Among these probes, the ASAPs, a series of voltage indicators based on a variant of circularly permuted green fluorescent protein (cpGFP) and a conjugated voltage sensitive domain (VSD), are capable of detecting both action potentials and subthreshold neuronal activities. Here we show that the ASAPs, when excited by blue light, undergo reversible photobleaching. We find that this fluorescence loss induced by excitation with 470-nm light can be substantially reversed by low-intensity 405-nm light. We demonstrate that 405-nm and 470-nm co-illumination significantly improved brightness and thereby signal-to-noise ratios during voltage imaging compared to 470-nm illumination alone. Illumination with a single wavelength of 440-nm light also produced similar improvements. We hypothesize that reversible photobleaching is related to cis-trans isomerization and protonation of the GFP chromophore of ASAP proteins. Amino acids that influence chromophore isomerization are potential targets of point mutations for future improvements.

In this paper, a novel depth acquisition algorithm aiming to obtain high resolution of dense depth maps based on lasers is proposed. Which expands the projection range and improves the robustness. In addition, dithering projection and defocusing techniques are used by lasers with the improvement of the Diffraction Optical Elements (DOE) technology. Four patterns are projected onto the projects by the lasers and captured by camera, where three for three-step phase-shifting (TS-PS) patterns and the other one is for space stripe pattern. More important, the calibrated by the traditional methods are unavailable in the proposed devices. We propose an algorithm for obtaining intrinsic and extrinsic parameters of the system. A substantially different spatial stripe coding scheme is designed, which is utilized to assist in time coding (TS-PS) solving depth information. We proposed a novel phase unwrapping method to obtain accurate absolute phase map. In addition, to further boost the performance, we utilized Weighted Least Squares (WLS) strategy to optimize the detail of the depth map based on color image. Thereby high resolution, detail and dense depth map obtained. Compared with the current methods, the robustness of our method is improved which will be extended to more scenes. The quantitative and qualitative evaluation experiments demonstrate that the proposed algorithm consistently produces better quality dense and higher resolution depth maps, superior to the current depth sensor. Keywords: Dithering defocusing techniques, Phase-shifting, Space stripe, WLS

Abstract This paper investigates the design of disturbance attenuating controller for memristive recurrent neural networks (MRNNs) with mixed time-varying delays. By applying the combination of differential inclusions, set-valued maps and Lyapunov–Razumikhin, a feedback control law is obtained in the simple form of linear matrix inequality (LMI) to ensure disturbance attenuation of memristor-based neural networks. Finally, a numerical example is given to show the effectiveness of the proposed criteria.

AIM: To investigate the relationship between serum levels of oxidation and inflammatory factors in type 2 diabetic patients with retinopathy and its clinical significance. METHODS: Totally 54 cases of patients with diabetic retinopathy was selected as subjects, including 31 patients with diabetes and non-proliferative retinopathy(NPDR group)and 23 patients with diabetes and proliferative retinopathy(PDR group). Another 30 cases of diabetes patients without DR(DM group)and 30 normal people(NC group)was selected as control. The level of fasting blood glucose(FPG), 2h postprandial blood glucose(2hPG), glycosylated hemoglobin(HbA1c), serum malondialdehyde(MDA)and heme oxygenase -1(HO-1), tumor necrosis factor α(TNF-α)and interleukin-6(IL-6)and C reactive protein(CRP)was detected, and variance test detect the difference between 4 groups, and SNK-Q was used to multiple comparison. Pearson correlation analysis was used to compare the correlation between oxidation markers(MDA and Ho-1)and the level of inflammatory factors(TNF-α, IL-6 and CRP). COX multivariate analysis was used to investigate the risk and protective factors of diabetic retinopathy. RESULTS: The levels of FPG, 2hPG, HbA1c, MDA, TNF-α, IL-6 and CRP in DM group, PDR group and NPDR group were significantly higher than that in NC group(PPPPPPPPCONCLUSION: Oxidative stress is closely related to the expression of inflammatory factors in serum of patients with diabetes mellitus, and is an important risk factor of DR, and related indicators can be used as markers for DR diagnosis.

Critical dynamic stress (σcri) and accumulative plastic strain (εp) are primary indicators regarding the dynamic stability of unbound granular materials (UGMs). This study aims to seek an effective method to evaluate the dynamic stability of UGMs used in railway subgrades. First, the dynamic characteristics of an UGM used in railway subgrade bed construction were investigated by performing a series of large-scale cyclic triaxial tests, with the results showing that εp versus cycle number (N) curves can be categorized into stable, failure, and critical patterns. Grey relational analyses were then established, where the analyzed results demonstrated that the εp–N curve pattern and final accumulative plastic strain (εs) of the stable curves are strongly correlated with the moisture content (w), confining pressure (σ3), and dynamic deviator stress (σd). The analyzed grey relational grades distributed in a narrow range of 0.72 to 0.81, indicating that w, σ3, and σd have similar degrees of importance on determining the εp–N curve patterns and the values of εs of the UGM. Finally, a data processing method using a back-propagation (BP) neural network is introduced to analyze the test data, and an empirical approach is developed to evaluate the σcri (considering the effects of σ3 and w) and εs (considering the effects of σ3, w, and σd) of the UGM. The analyzed results illustrated that the developed method can effectively reflect the linear/non-linear relationships of σcri and εs with respect to σ3 and/or σd. The σcri approximately increases linearly with increasing σ3, and a simple empirical formula is proposed for the σcri. In addition, εs and its variation rate increase non-linearly with increasing σd but decrease non-linearly as σ3 increases.

The novel coronavirus pneumonia (COVID-19) pandemic is a great threat to human society and now is still spreading. Although several vaccines have been authorized for emergency use, only one recombinant subunit vaccine has been permitted for widespread use. More subunit vaccines for COVID-19 should be developed in the future. The receptor binding domain (RBD), located at the S protein of SARS-CoV-2, contains most of the neutralizing epitopes. However, the immunogenicity of RBD monomers is not strong enough. In this study, we fused the RBD-monomer with a modified Fc fragment of human IgG1 to form an RBD-Fc fusion protein. The recombinant vaccine candidate based on the RBD-Fc protein could induce high levels of IgG and neutralizing antibody in mice, and these could last for at least three months. The secretion of IFN-γ, IL-2 and IL-10 in the RBD-stimulated splenocytes of immunized mice also increased significantly. Our results first showed that the RBD-Fc vaccine could induce both humoral and cellular immune responses and might be an optional strategy to control COVID-19.

This research aimed to investigate the effect of fine aggregate particles on mechanical properties of fly ash-based geopolymer mortar. In this work, seven kinds of river sand particles were designed based on different fine aggregate characteristics. The fineness modulus was adopted to quantitatively describe the gradation of sands. The fluidity, compressive, flexural, and tensile strengths of geopolymer mortar with different sand gradations were analyzed by laboratory tests. Furthermore, the composition and morphology of fly ash-based geopolymer mortar was analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The reasonable gradation range and filling effect of sand were obtained. The results show that fluidity and compressive and flexural strengths of geopolymer mortar both improve with the increase of the fineness modulus, while specific surface area and voidage are opposite. The tensile strength of mortar largely lies on the interface properties between the geopolymer binder and fine aggregates. When the pass rate of the key sieving size 1.18 mm is 75–95%, the pass rate of the key sieving size 0.15 mm is 15–25%, the fineness modulus is 2.2–2.6 and the appropriate filling coefficient of geopolymer paste is around 1.0–1.15, the comprehensive performance of geopolymer mortar is the best. This research paper could provide a basis for the design of geopolymer mortar based on fly ash, and it is of great significance for its popularization and application.

Based on analysis of horizontal well data characteristics, the differences of data distribution and variogram between vertical and horizontal wells in MPE3 oil field of Orinoco heavy oil belt were compared, and modeling strategies were proposed to cope with the big data paradox when data of horizontal wells was used directly into geologic modeling. The study shows the horizontal wells in the study area contain a large quantity of information, strong directionality of well trajectories and high drilling ratio of sandstone, causing variogram analysis result unconformable to the geologic understanding, and in turn making errors in the modeling of sedimentary microfacies and reservoir physical properties and prediction of probabilistic reserves. Firstly, the distributary channel distribution variogram was analyzed with data of vertical wells, and then the lithofacies framework was established under the control of the sedimentary facies and seismic data. After that, the horizontal wells data revealing high heterogeneity accuracy of reservoir, was combined with the vertical wells data to analyze argillaceous interlayer variograms and the corresponding reservoir lithofacies models were constructed. Finally, reservoir physical property models were generated and the geological reserves were calculated by wellblocks. This reservoir modeling method does not only reflect the geologic features underground, but also improve the accuracy of inter-well sand body prediction, and enhance the reliability of reservoir geologic model ultimately. Key words: horizontal well, geological modeling, big data paradox, big data analysis, variogram

Abstract Due to their mechanical and physical properties, aluminium alloys possess wide potential in the automotive industry, particularly in hot reciprocating applications such as pistons for diesel and petrol engines. WS2 particle-reinforced composites could bring further improvements by reducing friction and wear between moving parts. Reducing friction improves efficiency by lowering energy/fuel use, ultimately leading to lower greenhouse gas emissions, while antiwear properties can prolong component life. This study compares for the first time the tribological performance of powder metallurgy-consolidated Al composites reinforced with either IF- or 2H-WS2 particles, so as to elucidate their mechanism of action in test conditions similar to those encountered in engine applications. The composites were tested in lubricated reciprocating contacts against AISI52100 steel balls and the impact of WS2 could be seen at both 25 and 100 °C. The reduced friction and wear at ambient temperature is due to the predominantly physical mechanism of action of WS2, while the best antiwear performance is measured at elevated (standard operating engine) temperatures that promote the chemical reaction of WS2 with the aluminium matrix. The investigation focused on studying the wear tracks/scars and the tribofilms generated on the composite and ball with optical profilometry, SEM, XPS and Auger spectroscopy.

Abstract In this paper, we give a complete analysis of the equilibrium points of background neural networks with uniform firing rates. By using continuity, monotonicity of some functions and Rolle’s theorem, the number of equilibrium points and their locations are obtained. Moreover, some novel sufficient conditions are given to guarantee the stability of the equilibrium points for the network model by utilizing Taylor’s theorem. A simulation example is conducted to illustrate the theories developed in this paper.

We detected Chuzan virus (CHUV) in domestic yaks from the Qinghai-Tibetan Plateau, western China, indicating CHUV probably has been transmitted to yaks in recent years. Awareness for CHUV surveillance and transmission and livestock health management in these special regions should be raised to avoid outbreaks and animal loss.

We used the APSIM-Maize model to simulate maize potential yield (Yp) and rain-fed yield (Yw) when adaptation options of sowing date and planting density were adopted under Representative Concentration Pathway (RCP) 4.5 and 8.5 in the Guanzhong Plain of China. The results showed that Yp would decrease by 10.6–14.9% and 15.0–31.4% under RCP4.5 and RCP8.5 for summer maize, and 13.9–19.7% and 18.5–36.3% for spring maize, respectively. The Yw would decrease by 17.1–19.0% and 23.6–41.1% under RCP4.5 and RCP8.5 for summer maize, and 20.9–24.5% and 27.8–45.5% for spring maize, respectively. The loss of Yp and Yw could be reduced by 2.6–9.7% and 0–9.9%, respectively, under future climate for summer maize through countermeasures. For spring maize, the loss of Yp was mitigated by 14.0–25.0% and 2.0–21.8% for Yw. The contribution of changing sowing date and plant density on spring maize yield was more than summer maize, and the optimal adaptation options were more effective for spring maize. Additionally, the influences of changing sowing date and planting density on yields become weak as climate changes become more severe. Therefore, it is important to investigate the potential of other adaptation measures to cope with climate change in the Guanzhong Plain of China.

This study seeks to understand the reality and psychological difficulties faced by university graduates in Wuhan after the COVID-19 epidemic was controlled. Methods: A total of 6,417 graduate students were surveyed through an online questionnaire from late May to early June 2020. The questionnaire asked questions on depression, anxiety, insomnia, and suicidal behavior. In addition, self-administered epidemic-related questionnaires consisting of eight items were collected from university graduates. Results: Participants' positive detection rates for depression, anxiety, insomnia, and suicidal behavior are 13.4%, 8.3%, 4.4%, and 12.1%, respectively. The three biggest challenges faced by graduates are future development, economic difficulties, and employment problems. Conclusion: The detectable rate of depression, anxiety, and insomnia is low, and the detectable rate of suicide symptoms should be given more attention. The biggest problem of this group is their future development, and what they want to solve the most is the economic difficulty.

This paper proposes a moving-target tracking algorithm that measures the pose of a micro-robot with high precision and high speed using the Kalman filter-based kernelized correlation filter (K2CF) algorithm. The adaptive Kalman filter can predict the state of linearly and nonlinearly fast-moving targets. The kernelized correlation filter algorithm then accurately detects the positions of the moving targets and uses the detection results to modify the moving states of the targets. This paper verifies the performance of the algorithm on a monocular vision measurement platform and using a pose measurement method. The K2CF algorithm was embedded in the micro-robot’s attitude measurement system, and the tracking performances of three different trackers were compared under different motion conditions. Our tracker improved the positioning accuracy and maintained real-time operation. In a comparison study of K2CF and many other algorithms on Object Tracking Benchmark-50 and Object Tracking Benchmark-100 video sequences, the K2CF algorithm achieved the highest accuracy. In the 400 mm × 300 mm field of view, when the target radius is about 3 mm and the inter-frame acceleration displacement does not exceed 5.6 mm, the root-mean-square error of position and attitude angle can satisfy the precision requirements of the system.