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Downgoing/upgoing P/S-wave decomposition of ocean-bottom seismic (OBS) multicomponent data can help suppress the water-layer multiples and cross-talks between P- and S-waves, and therefore plays an important role in seismic migration and construction of P- and S-wave velocity models. We proposed novel composite calibration filters by introducing an additional dimension to the calibration of the particle velocity components, extending the wave-equation-based adaptive decomposition method. We also modified the existing workflow by jointly using primary reflections at near-to-medium offsets and ocean-bottom refractions at far offsets in the calibration optimization. The decomposition scheme with the novel calibration filters yielded satisfactory results in a deep-water OBS field data decomposition example. Expected decomposition effects, such as the enhancement of primary reflections and the attenuation of water-layer multiple events, can be observed in the decomposed upgoing wavefields. An experiment illustrated the effectiveness of composite calibration filters that compensated for unexpected velocity errors along the offset dimension.

The scraper conveyor is the key coal transportation equipment on the coal mining face. The conveyor often encounters the influence of abnormal working conditions, such as stuck chains, broken chains, and impact loads, which have a great effect on the smooth operation of the scraper chain and seriously affect the safety of coal production. If the chain breaks during the test, the broken link may fly out and hurt the tester. The test risk of the scraper conveyor under abnormal working conditions is relatively large; hence, the test research is impossible to carry out. The combination of experiment and simulation is used to carry out the research. The dynamic characteristic test bed of the chain drive system is created to collect the speed of the sprocket and the acceleration of the scraper. The two groups of data are obtained by simulation, and the accuracy of the simulation is verified by comparing the test data with the simulation data. The dynamic characteristics of the chain drive system under abnormal working conditions are analyzed by simulation. Results show that the longitudinal velocity of the link dramatically changes, the contact force increases by 5.4 times, and the link vibrates under impact loads. When the chain is stuck, the speed of the running direction suddenly changes, and the chainring vibrates. The contact force between the chainrings increases by 7.2 times compared with the smooth operation. When the chain is broken, the acceleration in the running direction of the link dramatically changes. This study provides a basis and reference for the further optimization design of the chain drive system and detection of the abnormal working conditions.

As an important source of cholinesterase inhibitors, alkaloids in natural products have high potential value in terms of exerting pharmacological activities. In this study, a strategy for targeted preparation of cholinesterase inhibitors in Uncaria rhynchophlly (Miq.) Miq. ex Havil (UR) by high-speed counter-current chromatography was provided. In the method, a two-phase polar solvent system composed of ethyl acetate/n-butanol/water (1:4:5, v/v/v) was used, which isolated five alkaloids from the UR extract for the first time. All alkaloids were identified by HR-ESI-MS and NMR as 7-epi-javaniside (1), vincosamide (2), strictosamide (3), cadambine (4), and 3α-dihydrocadambine (5). The poorly resolved compounds 2 and 3 were separated by preparative HPLC (prep-HPLC). Among them, compounds 1, 4, and 5 were firstly obtained from UR. The purity of these plant isolates was 98.8%, 98.7%, 99.2%, 95.7%, and 98.5%, respectively. Compounds 1–5 exhibited an inhibitory effect on acetyl-cholinesterase and butyryl-cholinesterase with an IC50 from 1.47 to 23.24 µg/mL and 1.01 to 18.24 µg/mL. Molecular docking and inhibitory activities indicated that compound 1 showed stronger inhibitory activity on acetyl-cholinesterase and butyryl-cholinesterase.

Bacillus cereus is one of the most important foodborne pathogenic microorganisms, which can lead to gastrointestinal and non-gastrointestinal diseases. However, the potential risk of B. cereus in aquatic products in China has not been comprehensively evaluated yet. In this study, a total of 860 aquatic samples from three types of retail aquatic products were collected from 39 major cities in China from 2011 to 2016. The contamination, distribution of virulence genes, antibiotic resistance and genetic diversity of B. cereus isolates were measured and analyzed. Of all the samples, 219 (25.47%) were positive for B. cereus and 1.83% (4/219) of the samples had contamination levels of more than 1,100 most probable number (MPN)/g. Different isolates had virulence potential, within which 59.6% (164/275) contained all three kinds of enterotoxin genes (nhe, hbl, and cytK-2) and 5.1% (14/275) possessed cereulide encoding gene cesB. The antimicrobial resistance profiles revealed the universal antibiotic resistance to rifampin and most β-lactams, suggesting the necessity to continuously monitor the antibiotic resistance of B. cereus in aquatic products and to control drug use in aquaculture. In sum, our study indicates the potential hazards of B. cereus isolated from aquatic products to customers and may provide a reference for clinical treatment caused by B. cereus.

Fms-like tyrosine kinase 3 (FLT3) mutation is one of the most common mutations in acute myeloid leukemia (AML). However, the effect of FLT3 mutation on survival is currently still controversial and the leukemogenic mechanisms are still under further investigation. The aim of our study is to identify differentially expressed genes (DEGs) in FLT3-mutant AML and to find crucial DEGs whose expression level is related to prognosis for further analysis. By mining the TCGA-LAML dataset, 619 differentially expressed lncRNAs (DElncRNAs) and 1,428 differentially expressed mRNAs (DEmRNAs) were identified between FLT3-mutant and FLT3-wildtype samples. Through weighted gene correlation network analysis (WGCNA) and the following Cox proportional hazards regression analysis, we constructed the prognostic risk models to identify the hub DElncRNAs and DEmRNAs associated with AML prognosis. The presence of both SH3TC2 divergent transcript (SH3TC2-DT) and SH3TC2 in respective prognostic risk models promotes us to further study the significance of this gene pair in AML. SH3TC2-DT and SH3TC2 were identified to be coordinately high expressed in FLT3-mutant AML samples. High expression of this gene pair was associated with poor survival. Using logistic regression analysis, we found that high SH3TC2-DT/SH3TC2 expression was associated with FLT3 mutation, high WBC count, and intermediate cytogenetic and molecular–genetic risk. AML with SH3TC2-DT/SH3TC2 high expression showed enrichment of transcripts associated with stemness, quiescence, and leukemogenesis. Our study suggests that the SH3TC2-DT/SH3TC2 gene pair may be a possible biomarker to further optimize AML prognosis and may function in stemness or quiescence of FLT3-mutant leukemic stem cells (LSCs).

The increased PD-L1 expression induces poorer prognosis in melanoma. The small molecule inhibitors of PD-1/PD-L1 pathways have been an encouraging drug development strategy because of good affinity and oral bioavailability without immunogenicity and immunotoxicities of PD-1/PD-L1 antibodies. In this study, we studied the effects of PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, on PD-1/PD-L1 binding and the cytokines secretion in human CD3+ cells in vitro. We also investigated the antitumor and immunomodulatory activity of PCC0208025 and the pharmacokinetics properties in B16-F10 melanoma-bearing mice. The results showed that PCC0208025 inhibited the PD-1/PD-L1 proteins binding, and rescued PD-L1-mediated inhibition of IFN-γ production in human CD3+ T cells in vitro. Furthermore, in B16-F10 melanoma-bearing mice, PCC0208025 presented the antitumor effects, enhanced IFN-γ levels in plasma, increased the frequency of CD3+CD8+ T and CD8+IFN-γ+ T and the ratios of CD8+/Treg, and deceased the CD4+CD25+CD127low/- (Treg) number in tumor. Pharmacokinetics study found that PCC0208025 was absorbed and distributed into the tumors with much higher concentrations than those of the blockade against PD-1/PD-L1 binding. Our work suggests that PCC0208025 exhibited anti-tumor effects through inhibiting Treg expansion and increasing cytotoxic activity of tumor-infiltrating CD8+ T cells by the blockade of PD-1/PD-L1 binding, which may provide the pharmacological basis to develop small molecule inhibitors of PD-1/PD-L1 binding for PCC0208025 as a lead compound.

Bacillus cereus is widely distributed in different food products and can cause a variety of symptoms associated with food poisoning. Since ready-to-eat (RTE) foods are not commonly sterilized by heat treatment before consumption, B. cereus contamination may cause severe food safety problems. In this study, we investigated the prevalence of B. cereus in RTE food samples from different regions of China and evaluated the levels of bacterial contamination, antibiotic resistance, virulence gene distribution, and genetic polymorphisms of these isolates. Of the tested retail RTE foods, 35% were positive for B. cereus, with 39 and 83% of the isolated strains harboring the enterotoxin-encoding hblACD and nheABC gene clusters, respectively. The entFM gene was detected in all B. cereus strains. The cytK gene was present in 68% of isolates, but only 7% harbored the emetic toxin-encoding gene cesB. Antimicrobial susceptibility testing revealed that the majority of the isolates were resistant not only to most β-lactam antibiotics, but also to rifamycin. Multilocus sequence typing (MLST) revealed that the 368 isolates belonged to 192 different sequence types (STs) including 93 new STs, the most prevalent of which was ST26. Collectively, our study indicates the prevalence, bacterial contamination levels, and biological characteristics of B. cereus isolated from RTE foods in China and demonstrates the potential hazards of B. cereus in RTE foods.

Abstract Background Orientation field (OF) plays a very significant role in automatic fingerprint recognition systems. Many algorithms have been proposed for the estimation of fingerprints’ OF but it is hard to solve the dilemma of correcting spurious ridge structure and avoiding singularity location deviation, especially for poor images. So far, the following drawbacks still need to be solved for OF construction methods for practical application: (1) How to adaptively choose block scales to resolve the contradiction between accuracy and anti-noise, since small scale is beneficial to accuracy but is sensitive to noise, while large scale is more resistant to noise, but the accuracy is deteriorated. (2) How to construct the genuine OF in the areas close-by singular points and to evade singularity location deviation? Current block based methods give spurious OF estimates in the area near singular points because these areas have large curvature thus the detected singular points deviate from the genuine localizations. When these singular points are used as the anchor for referencing minutiae, it makes the average error of matching or recognition even larger. Therefore, it is essentials to construct the genuine OF in the areas close-by singular points and to evade singularity deviation. Methods To overcome the above-mentioned limitations, a novel method, combining a weighted multi-scale composite window (WMCM) with a hierarchical smoothing strategy has been proposed for the computation of fingerprint OF. This method mainly contains two procedures: the approximate OF estimation and the hierarchical OF smoothing. In the first procedure, a series of OFs are established under multiple scales of composite windows by using a gradient based method then a coarse OF is estimated using the weight of each scale determined by a squared gradient consistency. In the second procedure, the OF is first quantized into a two-digitized orientation zone and a two-orientation-zone filtering strategy is adapted to the OF blocks based on a filtering mask obtained after eliminating the isolated blocks. In the end a similar three-digitized orientation zone is performed to obtain an accurate and smooth OF. To validate the performance, the proposed method has been applied to OF computation using the FVC2004 databases and three experiments are designed. Experiment 1 aims to validate whether the weighted multi-scale composite window can balance the dilemma of accuracy and robustness more effectively than the previous works do. Experiment 2 is designed to examine whether the hierarchical smoothing method can correct the spurious ridge flow and preserve the genuine localization of singular points. The purpose of experiment 3 is to test the performance of the proposed method on OF reconstruction in low quality fingerprint images. The fingerprint databases FVC 2004 DB1–DB4 are employed in this study. Results The results of experiment I shows that the proposed method is capable to extract the information of OF reliably and it is more robust against singularity localization deviation in comparison with the other three gradient based methods. The results of experiment II indicates that the proposed smoothing method can balance the contradiction in correcting spurious ridge structures and preserving genuine singularity localization. The results of experiment III illustrates that our approach combing WMCW with the hierarchical smoothing method is capable to extract the information of OF ridge reliably and it is more robust against singularity deviation in comparison with the other three gradient based methods. In a word, the experiment results demonstrate that the proposed method can correct spurious ridge structure and meanwhile avoid singularity deviation compared with the previous works. Conclusions A novel gradient based algorithm has been proposed which is more reliable for the estimation of the ridge information for fingerprint OF and is more accurate in preserving the singularity localization. Compared with the previously proposed gradient based methods, the advantages of the proposed RBSF lie in three aspects. Firstly a weighted multi-scale composite window is put forward to replace the single window used by conventional gradient based methods and to adaptively choose the scales of the blocks. Secondly, a hierarchical smoothing strategy is proposed to enhance the OF by using the two-orientation-zone filtering and the three-orientation-zone filtering, aiming to correct the spurious ridges and preserving the genuine location of singular points. Finally, three experiments are designed to test the proposed algorithm together with other popular gradient based methods on real fingerprint images, which are selected from different categories and all are suffering from obvious noise effects. All the experiment results show that the proposed method is superior with respect to reliable OF construction and avoiding singularity localization deviation.

Abstract On August 8, 2017, the Jiuzhaigou Mw 6.5 earthquake occurred in Sichuan province, southwestern China, along the eastern margin of the Tibetan Plateau. The epicenter is surrounded by the Minjiang, Huya, and Tazang Faults. As the seismic activity and tectonics are very complicated, there is controversy regarding the accurate location of the epicenter and the seismic fault of the Jiuzhaigou earthquake. To investigate these aspects, first, the coseismic deformation field was derived from Global Positioning System (GPS) and Interferometric Synthetic Aperture Radar (InSAR) measurements. Second, the fault geometry, coseismic slip model, and Coulomb stress changes around the seismic region were calculated using a homogeneous elastic half-space model. The coseismic deformation field derived from InSAR measurements shows that this event was mainly dominated by a left-lateral strike-slip fault. The maximal and minimal displacements were approximately 0.15 m and − 0.21 m, respectively, along line-of-sight observation. The whole deformation field follows a northwest-trending direction and is mainly concentrated west of the fault. The coseismic slip is 28 km along the strike and 18 km along the dip. It is dominated by a left-lateral strike-slip fault. The average and maximal fault slip is 0.18 and 0.85 m, respectively. The rupture did not fully reach the ground surface. The focal mechanism derived from GPS and InSAR data is consistent with the kinematics and geometry of the Huya Fault. Therefore, we conclude that the northern section or the Shuzheng segment of the Huya Fault is the seismogenic fault. The maximal fault slip is located at 33.25°N and 103.82°E at a depth of ~ 11 km, and the release moment is approximately 6.635 × 1018 Nm, corresponding to a magnitude of Mw 6.49, which is consistent with results reported by the US Geological Survey, Global Centroid Moment Tensor, and other researchers. The coseismic Coulomb stress changes enhanced the stress on the northwest and southeast edges of the northern extension of the Huya Fault. Seismic risks cannot be ignored in the future although aftershocks are fewer in number in these regions.

In this paper, an efficient method to produce a ZnO/BiOI nano-heterojunction is developed by a facile solution method followed by calcination. By tuning the ratio of Zn/Bi, the morphology varies from nanoplates, flowers to nanoparticles. The heterojunction formed between ZnO and BiOI decreases the recombination rate of photogenerated carriers and enhances the photocatalytic activity of ZnO/BiOI composites. The obtained ZnO/BiOI heterostructured nanocomposites exhibit a significant improvement in the photodegradation of rhodamine B under visible light (λ ≥ 420 nm) irradiation as compared to single-phase ZnO and BiOI. A sample with a Zn/Bi ratio of 3:1 showed the highest photocatalytic activity (≈99.3% after 100 min irradiation). The photodegradation tests indicated that the ZnO/BiOI heterostructured nanocomposites not only exhibit remarkably enhanced and sustainable photocatalytic activity, but also show good recyclability. The excellent photocatalytic activity could be attributed to the high separation efficiency of the photoinduced electron–hole pairs as well as the high specific area.

The kidneys are often involved in adverse effects and toxicity caused by exposure to foreign compounds, chemicals, and drugs. Early predictions of these influences are essential to facilitate new, safe drugs to enter the market. However, in current drug treatments, drug-induced nephrotoxicity accounts for 1/4 of reported serious adverse reactions, and 1/3 of them are attributable to antibiotics. Drug-induced nephrotoxicity is driven by multiple mechanisms, including altered glomerular hemodynamics, renal tubular cytotoxicity, inflammation, crystal nephropathy, and thrombotic microangiopathy. Although the functional proteins expressed by renal tubules that mediate drug sensitivity are well known, current in vitro 2D cell models do not faithfully replicate the morphology and intact renal tubule function, and therefore, they do not replicate in vivo nephrotoxicity. The kidney is delicate and complex, consisting of a filter unit and a tubular part, which together contain more than 20 different cell types. The tubular epithelium is highly polarized, and maintaining cellular polarity is essential for the optimal function and response to environmental signals. Cell polarity depends on the communication between cells, including paracrine and autocrine signals, as well as biomechanical and chemotaxis processes. These processes affect kidney cell proliferation, migration, and differentiation. For drug disposal research, the microenvironment is essential for predicting toxic reactions. This article reviews the mechanism of drug-induced kidney injury, the types of nephrotoxicity models (in vivo and in vitro models), and the research progress related to drug-induced nephrotoxicity in three-dimensional (3D) cellular culture models.

Abstract Bisphenol A (BPA), a member of the environmental endocrine disruptors (EDCs), has recently received increased attention because of its effects on brain insulin resistance. Available data have indicated that brain insulin resistance may contribute to neurodegenerative diseases. However, the associated mechanisms that underlie BPA-induced brain-related outcomes remain largely unknown. In the present study, we identified significant insulin signaling disturbances in the SH-SY5Y cell line that were mediated by BPA, including the inhibition of physiological p-IR Tyr1355 tyrosine, p-IRS1 tyrosine 896, p-AKT serine 473 and p-GSK3α/β serine 21/9 phosphorylation, as well as the enhancement of IRS1 Ser307 phosphorylation; these effects were clearly attenuated by insulin and rosiglitazone. Intriguingly, Alzheimer’s disease (AD)-associated pathological proteins, such as BACE-1, APP, β-CTF, α-CTF, Aβ 1–42 and phosphorylated tau proteins (S199, S396, T205, S214 and S404), were substantially increased after BPA exposure, and these effects were abrogated by insulin and rosiglitazone treatment; these findings underscore the specific roles of insulin signaling in BPA-mediated AD-like neurotoxicity. Thus, an understanding of the regulation of insulin signaling may provide novel insights into potential therapeutic targets for BPA-mediated AD-like neurotoxicity.

Abstract Fatty liver (FL) is one of the risk factors for acute pancreatitis and is also indicative of a worse prognosis as compared to acute pancreatitis without fatty liver (AP). The aim of the present study was to analyze, at the hepatic level, the differentially expressed genes (DEGs) between acute pancreatitis with fatty liver (APFL) rats and AP rats. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses of these DEGs indicated that PPARα signalling pathway and fatty acid degradation pathway may be involved in the pathological process of APFL, which indicated that fatty liver may aggravate pancreatitis through these pathways. Moreover, the excessive activation of JAK/STAT signaling pathway and toll-like receptor signaling pathway was also found in APFL group as shown in heat map. In conclusion, the inhibition of PPARα signaling pathway and the fatty acid degradation pathway may lead to the further disorder of lipid metabolism, which can aggravate pancreatitis.

Abstract Background Ultrasound imaging plays an important role in computer diagnosis since it is non-invasive and cost-effective. However, ultrasound images are inevitably contaminated by noise and speckle during acquisition. Noise and speckle directly impact the physician to interpret the images and decrease the accuracy in clinical diagnosis. Denoising method is an important component to enhance the quality of ultrasound images; however, several limitations discourage the results because current denoising methods can remove noise while ignoring the statistical characteristics of speckle and thus undermining the effectiveness of despeckling, or vice versa. In addition, most existing algorithms do not identify noise, speckle or edge before removing noise or speckle, and thus they reduce noise and speckle while blurring edge details. Therefore, it is a challenging issue for the traditional methods to effectively remove noise and speckle in ultrasound images while preserving edge details. Methods To overcome the above-mentioned limitations, a novel method, called Rayleigh-maximum-likelihood switching bilateral filter (RSBF) is proposed to enhance ultrasound images by two steps: noise, speckle and edge detection followed by filtering. Firstly, a sorted quadrant median vector scheme is utilized to calculate the reference median in a filtering window in comparison with the central pixel to classify the target pixel as noise, speckle or noise-free. Subsequently, the noise is removed by a bilateral filter and the speckle is suppressed by a Rayleigh-maximum-likelihood filter while the noise-free pixels are kept unchanged. To quantitatively evaluate the performance of the proposed method, synthetic ultrasound images contaminated by speckle are simulated by using the speckle model that is subjected to Rayleigh distribution. Thereafter, the corrupted synthetic images are generated by the original image multiplied with the Rayleigh distributed speckle of various signal to noise ratio (SNR) levels and added with Gaussian distributed noise. Meanwhile clinical breast ultrasound images are used to visually evaluate the effectiveness of the method. To examine the performance, comparison tests between the proposed RSBF and six state-of-the-art methods for ultrasound speckle removal are performed on simulated ultrasound images with various noise and speckle levels. Results The results of the proposed RSBF are satisfying since the Gaussian noise and the Rayleigh speckle are greatly suppressed. The proposed method can improve the SNRs of the enhanced images to nearly 15 and 13 dB compared with images corrupted by speckle as well as images contaminated by speckle and noise under various SNR levels, respectively. The RSBF is effective in enhancing edge while smoothing the speckle and noise in clinical ultrasound images. In the comparison experiments, the proposed method demonstrates its superiority in accuracy and robustness for denoising and edge preserving under various levels of noise and speckle in terms of visual quality as well as numeric metrics, such as peak signal to noise ratio, SNR and root mean squared error. Conclusions The experimental results show that the proposed method is effective for removing the speckle and the background noise in ultrasound images. The main reason is that it performs a “detect and replace” two-step mechanism. The advantages of the proposed RBSF lie in two aspects. Firstly, each central pixel is classified as noise, speckle or noise-free texture according to the absolute difference between the target pixel and the reference median. Subsequently, the Rayleigh-maximum-likelihood filter and the bilateral filter are switched to eliminate speckle and noise, respectively, while the noise-free pixels are unaltered. Therefore, it is implemented with better accuracy and robustness than the traditional methods. Generally, these traits declare that the proposed RSBF would have significant clinical application.

Histone citrullination regulates diverse cellular processes. Here, we report that SMARCAD1 preferentially associates with H3 arginine 26 citrullination (H3R26Cit) peptides present on arrays composed of 384 histone peptides harboring distinct post-transcriptional modifications. Among ten histone modifications assayed by ChIP-seq, H3R26Cit exhibited the most extensive genomewide co-localization with SMARCAD1 binding. Increased Smarcad1 expression correlated with naive pluripotency in pre-implantation embryos. In the presence of LIF, Smarcad1 knockdown (KD) embryonic stem cells lost naive state phenotypes but remained pluripotent, as suggested by morphology, gene expression, histone modifications, alkaline phosphatase activity, energy metabolism, embryoid bodies, teratoma, and chimeras. The majority of H3R26Cit ChIP-seq peaks occupied by SMARCAD1 were associated with increased levels of H3K9me3 in Smarcad1 KD cells. Inhibition of H3Cit induced H3K9me3 at the overlapping regions of H3R26Cit peaks and SMARCAD1 peaks. These data suggest a model in which SMARCAD1 regulates naive pluripotency by interacting with H3R26Cit and suppressing heterochromatin formation.

Emerging evidence has shown that cinobufagin, as an active ingredient of Venenum Bufonis, inhibits tumor development. The aim of this study was to investigate the inhibitory effects of cinobufagin on A375 human malignant melanoma cells. MTT and colony formation assays showed that cinobufagin significantly inhibited A375 cell proliferation and cell colony formation. Additional studies demonstrated that cinobufagin markedly increased the levels of ATM serine/threonine kinase (ATM) and checkpoint kinase 2 (Chk2) and decreased the levels of cell division cycle 25C (CDC25C), cyclin-dependent kinase 1 (CDK1), and cyclin B, subsequently inducing G2/M cell cycle arrest in A375 cells. Moreover, cinobufagin clearly inhibited the levels of phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), AKT, p-AKT, and B-cell lymphoma 2 (Bcl-2). By contrast, it increased the levels of Bcl-2-associated death promoter, Bcl-2-associated X, cytoplasmic cytochrome C, and apoptotic protease activating factor 1, leading to increased levels of cleaved caspase-9 and cleaved caspase-3, resulting in the apoptosis of A375 cells. Together, these results indicate that cinobufagin can induce cell cycle arrest at the G2/M phase and apoptosis, leading to inhibition of A375/B16 cell proliferation. Thus, cinobufagin may be useful for melanoma treatment.

Bacillus cereus is a food-borne opportunistic pathogen that can induce diarrheal and emetic symptoms. It is widely distributed in different environments and can be found in various foods, including fresh vegetables. As their popularity grows worldwide, the risk of bacterial contamination in fresh vegetables should be fully evaluated, particularly in vegetables that are consumed raw or processed minimally, which are not commonly sterilized by enough heat treatment. Thereby, it is necessary to perform potential risk evaluation of B. cereus in vegetables. In this study, 294 B. cereus strains were isolated from vegetables in different cities in China to analyze incidence, genetic polymorphism, presence of virulence genes, and antimicrobial resistance. B. cereus was detected in 50% of all the samples, and 21/211 (9.95%) of all the samples had contamination levels of more than 1,100 MPN/g. Virulence gene detection revealed that 95 and 82% of the isolates harbored nheABC and hblACD gene clusters, respectively. Additionally, 87% of the isolates harbored cytK gene, and 3% of the isolates possessed cesB. Most strains were resistant to rifampicin and β-lactam antimicrobials but were sensitive to imipenem, gentamicin, ciprofloxacin, kanamycin, telithromycin, ciprofloxacin, and chloramphenicol. In addition, more than 95.6% of the isolates displayed resistance to three kinds of antibiotics. Based on multilocus sequence typing, all strains were classified into 210 different sequence types (STs), of which 145 isolates were assigned to 137 new STs. The most prevalent ST was ST770, but it included only eight isolates. Taken together, our research provides the first reference for the incidence and characteristics of B. cereus in vegetables collected throughout China, indicating a potential hazard of B. cereus when consuming vegetables without proper handling.

In this work, we designed and synthesized four bipolar blue-emitting materials with carbazole, imidazole, and biphenyl as donor, acceptor, and p bridge, respectively. The twisted phenylimidazole acceptor leads to a wider band-gap and hence deeper blue emission than the conjugated phenanthrimidazole acceptor. For the substituents on the carbazole donor, the t-butyl group could prevent the intramolecular charge transfer (ICT) process more effectively than the methoxy group. A non-doped deep-blue organic light-emitting diodes (OLED) is obtained with CIE coordinates of (0.159, 0.080), a maximum luminance of 11,364 cd/m2, and a maximum EQE of 4.43%.

The flexoelectricity, which is a new electromechanical coupling phenomenon between strain gradients and electric polarization, has a great influence on the fracture analysis of flexoelectric solids due to the large gradients near the cracks. On the other hand, although the flexoelectricity has been extensively investigated in recent decades, the study on flexoelectricity in nonhomogeneous materials is still rare, especially the fracture problems. Therefore, in this manuscript, the conservation integrals for nonhomogeneous flexoelectric materials are obtained to solve the fracture problem. Application of operators such as grad, div, and curl to electric Gibbs free energy and internal energy, the energy-momentum tensor, angular momentum tensor, and dilatation flux can also be derived. We examine the correctness of the conservation integrals by comparing with the previous work and discuss the operator method here and Noether theorem in the previous work. Finally, considering the flexoelectric effect, a nonhomogeneous beam problem with crack is solved to show the application of the conservation integrals.

Glycoprotein G (gG) from herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, respectively) functions as a viral chemokine binding protein (vCKBP). Soluble recombinant forms of gG of HSV-1 and HSV-2 (SgG1 and SgG2, respectively) enhance chemokine-mediated leukocyte migration, in contrast to most known vCKBPs, including those from animal alpha-herpesviruses. Furthermore, both proteins bind to nerve growth factor (NGF), but only SgG2 enhances NGF-dependent neurite outgrowth. The basis and implications of this functional difference between the two proteins are still unknown. While gG1 and gG2 are positional homologues in the genome, they share very limited sequence homology. In fact, US4, the open reading frame encoding gG is the most divergent genetic locus between these viruses. Full-length gG1 and gG2 are type I transmembrane proteins located on the plasma membrane of infected cells and at the viral envelope. However, gG2 is larger than gG1 and is cleaved during protein maturation, secreting the N-terminal domain to the supernatant of infected cells, whereas gG1 is not. The enzyme involved in gG2 cleavage and the functional relevance of gG2 cleavage and secretion are unknown. We aim to identify the gG2 sequence required for cleavage to determine its functional role in future experiments. Our results prove the existence of at least two cleavage motifs in gG2 within the amino acid region 314-343. Transfer of this sequence to a fusion protein results in cleavage. Finally, we show that propeptide convertases like furin are responsible for gG2 cleavage.

Current methods for mapping RNA-RNA interactions have to rely on an ‘anchor’ protein or RNA. Here, the authors report the MARIO (Mapping RNA interactome in vivo) technology that can massively reveal RNA-RNA interactions and RNA structure from unperturbed cells.

The microflower-like Si/MoS2 composites were fabricated using Si quantum dots (QDs) to assist a facile hydrothermal method. The electrochemical performance of Si/MoS2 composite in symmetric and asymmetric systems was studied. Electrochemical characterization revealed that the Si/MoS2 composite electrode in a three-electrode system has a high specific capacitance of 574.4 F·g−1 at 5 A·g−1. Furthermore, the Si/MoS2 composite electrode in a two-electrode system had the maximum energy density of 27.2 Wh·kg−1 when a power density of 749.1 W·kg−1 was achieved. Therefore, this investigation proves the Si/MoS2 composite microflower-like structure should be a promising candidate electrode material for supercapacitors.

With many advantages, modular multilevel convert (MMC) has been extensively used in high and medium voltage power transmission projects. The thermal performance and reliability of components in MMC are key issues in system operation. However, in the current research on the reliability of MMC components, there are few methods to improve service lifetime expectancy of the components. This paper proposes a balance control algorithm, based on the cumulative fatigue damage of components, feedback to the control terminal for allocating the sub-module (SM) operating state and generating trigger pulses. Finally, the effectiveness of the proposed algorithm is verified and discussed in case studies. It is found that this algorithm is able to improve the aging degree of components in the meanwhile, the improvement in MMC reliability comes at the cost of slightly increasing capacitor voltage fluctuations and total harmonic distortion (THD). Due to the limitation of capacitor thermal performance, SM capacitor banks become a weak link in MMC reliability.

Bacillus cereus is a common and important food-borne pathogen that can be found in various food products. Due to low-temperature sterilization for a short period of time, pasteurization is not sufficient for complete elimination of B. cereus in milk, thereby cause severe economic loss and food safety problems. It is therefore of paramount importance to perform risk assessment of B. cereus in pasteurized milk. In this study, we isolated B. cereus from pasteurized milk samples in different regions of China, and evaluated the contamination situation, existence of virulence genes, antibiotic resistance profile and genetic polymorphism of B. cereus isolates. Intriguingly, 70 samples (27%) were found to be contaminated by B. cereus and the average contamination level was 111 MPN/g. The distribution of virulence genes was assessed toward 10 enterotoxigenic genes (hblA, hblC, hblD, nheA, nheB, nheC, cytK, entFM, bceT, and hlyII) and one emetic gene (cesB). Forty five percent strains harbored enterotoxigenic genes hblACD and 93% isolates contained nheABC gene cluster. The positive rate of cytK, entFM, bceT, hlyII, and cesB genes were 73, 96, 75, 54, and 5%, respectively. Antibiotic susceptibility assessment showed that most of the isolates were resistant to β-lactam antibiotics and rifampicin, but susceptible to other antibiotics such as ciprofloxacin, gentamicin and chloramphenicol. Total multidrug-resistant population was about 34%. In addition, B. cereus isolates in pasteurized milk showed a high genetic diversity. In conclusion, our findings provide the first reference on the prevalence, contamination level and characteristics of B. cereus isolated from pasteurized milk in China, suggesting a potential high risk of B. cereus to public health and dairy industry.

Effects of forming pores in Zr70Cu30 metallic glass on the deformation behaviour is investigated through molecular dynamics simulations. The formation of pores leads to only a small reduction in strength, but dramatically enhanced plasticity in compression. The large plasticity of glass is attributed to the large effective free space induced by forming pores. It can also promote formation of crystalline phases in the amorphous matrix during deformation. Simulation reproduces the images of the evolution of pores in the metallic glass. The simulation results are in good agreement with experimental results.

Lgr5+ supporting cells (SCs) are enriched hair cell (HC) progenitors in the cochlea. Both in vitro and in vivo studies have shown that HC injury can spontaneously activate Lgr5+ progenitors to regenerate HCs in the neonatal mouse cochlea. Promoting HC regeneration requires the understanding of the mechanism of HC regeneration, and this requires knowledge of the key genes involved in HC injury-induced self-repair responses that promote the proliferation and differentiation of Lgr5+ progenitors. Here, as expected, we found that neomycin-treated Lgr5+ progenitors (NLPs) had significantly greater HC regeneration ability, and greater but not significant proliferation ability compared to untreated Lgr5+ progenitors (ULPs) in response to neomycin exposure. Next, we used RNA-seq analysis to determine the differences in the gene-expression profiles between the transcriptomes of NLPs and ULPs from the neonatal mouse cochlea. We first analyzed the genes that were enriched and differentially expressed in NLPs and ULPs and then analyzed the cell cycle genes, the transcription factors, and the signaling pathway genes that might regulate the proliferation and differentiation of Lgr5+ progenitors. We found 9 cell cycle genes, 88 transcription factors, 8 microRNAs, and 16 cell-signaling pathway genes that were significantly upregulated or downregulated after neomycin injury in NLPs. Lastly, we constructed a protein-protein interaction network to show the interaction and connections of genes that are differentially expressed in NLPs and ULPs. This study has identified the genes that might regulate the proliferation and HC regeneration of Lgr5+ progenitors after neomycin injury, and investigations into the roles and mechanisms of these genes in the cochlea should be performed in the future to identify potential therapeutic targets for HC regeneration.

Exercise could afford multiple beneficial effects on obesity-related metabolic disorders. To address this issue, C57BL/6J mice were used to investigate the effects of 13 weeks of swim training on HFD-induced obesity and related insulin resistance and inflammation. Our results show that swim training can significantly prevent HFD-induced weight gain and increase resting energy expenditure without affecting food intake. The insulin sensitivity was enhanced in the HFD + swim group than in the HFD + sedentary group. Moreover, swim training considerably decreased serum LPS content and downregulates epididymis white adipose tissue (eWAT) expression of the inflammatory mediator Tnf-α, Il-6, and Mcp-1. In summary, 13 weeks of swim training could reverse HFD-induced metabolic disorders including insulin resistance and inflammation.

High-entropy alloys are a new type of material developed in recent years. It breaks the traditional alloy-design conventions and has many excellent properties. High-pressure treatment is an effective means to change the structures and properties of metal materials. The pressure can effectively vary the distance and interaction between molecules or atoms, so as to change the bonding mode, and form high-pressure phases. These new material states often have different structures and characteristics, compared to untreated metal materials. At present, high-pressure technology is an effective method to prepare alloys with unique properties, and there are many techniques that can achieve high pressures. The most commonly used methods include high-pressure torsion, large cavity presses and diamond-anvil-cell presses. The materials show many unique properties under high pressures which do not exist under normal conditions, providing a new approach for the in-depth study of materials. In this paper, high-pressure (HP) technologies applied to high-entropy alloys (HEAs) are reviewed, and some possible ways to develop good properties of HEAs using HP as fabrication are introduced. Moreover, the studies of HEAs under high pressures are summarized, in order to deepen the basic understanding of HEAs under high pressures, which provides the theoretical basis for the application of high-entropy alloys.

Nanocrystalline multivalent metal spinels are considered as attractive non-precious oxygen electrocatalysts. Identifying their active sites and understanding their reaction mechanisms are essential to explore novel transition metal (TM) oxides catalysts and further promote their catalytic efficiency. Here we report a systematic investigation, by means of soft X-ray absorption spectroscopy (sXAS), on cubic and tetragonal CoxMn3-xO4 (x = 1, 1.5, 2) spinel oxides as a family of highly active catalysts for the oxygen reduction reaction (ORR). We demonstrate that the ORR activity for oxide catalysts primarily correlates to the partial covalency of between O 2p orbital with Mn4+ 3d t2g-down/eg-up, Mn3+ 3d eg-up and Co3+ 3d eg-up orbitals in octahedron, which is directly revealed by the O K-edge sXAS. Our findings propose the critical influences of the partial covalency between oxygen 2p band and specific metal 3d band on the competition between intermediates displacement of the ORR, and thus highlight the importance of electronic structure in controlling oxide catalytic activity.

A NiO@ZnO (NZO) hybrid with different reaction times was successfully synthesized by a green hydrothermal method. After comparison, it was found that hydrothermal time had a great impact on specific capacitance. As a supercapacitor electrode of NZO-12h, it exhibited the maximum reversible specific capacitance of 985.0 F/g (3.94 F/cm2) at 5 mA/cm2 and 587.5 F/g (2.35 F/cm2) at 50 mA/cm2, as well as a high retention of 74.9% capacitance after 1500 cycles at 20 mA/cm2. Furthermore, the asymmetric electrode device with ZnO-12h and activated carbon (AC) as the positive and negative electrodes was successfully assembled. In addition, the device exhibited a specific capacitance of 85.7 F/g at 0.4 A/g. Moreover, the highest energy density of 27.13 Wh kg−1 was obtained at a power density of 321.42 W kg−1. These desirable electrochemical properties demonstrate that the NZO hybrid is a promising electrode material for a supercapacitor.

PFKFB3 (6-phosphofructo-2-kinase) synthesizes fructose 2,6-bisphosphate (F2,6P2), which is an allosteric activator of 6-phosphofructo-1-kinase (PFK-1), the rate-limiting enzyme of glycolysis. Overexpression of the PFKFB3 enzyme leads to high glycolytic metabolism, which is required for cancer cells to survive in the harsh tumor microenvironment. The objective of this study was to investigate the antitumor activity of PFK15 (1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one), a small molecule inhibitor of PFKFB3, against gastric cancer and to explore its potential mechanisms. The effects of PFK15 on proliferation, apoptosis and cell cycle progression in gastric cancer cells were evaluated by cytotoxicity and apoptosis assays, flow cytometry, and western blotting. In addition, the invasion inhibition effects of PFK15 were measured by transwell invasion assay and western blot analysis, and a xenograft tumor model was used to verify the therapeutic effect of PFK15 in vivo. Results showed that PFK15 inhibited the proliferation, caused cell cycle arrest in G0/G1 phase by blocking the Cyclin-CDKs/Rb/E2F signaling pathway, and induced apoptosis through mitochondria in gastric cancer cells. Tumor volume and weight were also significantly reduced upon intraperitoneal injection with PFK15 at 25 mg/kg. In addition, PFK15 inhibited the invasion of gastric cancer cells by downregulating focal adhesion kinase (FAK) expression and upregulating E-cadherin expression. Taken together, our findings indicate that PFK15 is a promising anticancer drug for treating gastric cancer.

A multi-step annealing method was successfully applied to inclusions reduction and resistivity improvement of CdMnTe:In (CMT:In) single crystals with high resistivity, including a Cd atmosphere annealing step followed by a Te atmosphere annealing step. After the Cd atmosphere annealing step, the density of Te inclusions was reduced distinctly, and it could be also decreased in the subsequent step of re-annealing under Te atmosphere. Both the resistivity and IR transmittance decreased notably after Cd atmosphere annealing, whereas they increased tremendously after re-annealing under a Te atmosphere. The reduction of full-width at-half-maximum (FWHM) and the increase of the intensity of the X-ray rocking curve indicated an improvement of the crystal quality. Meanwhile, after Cd atmosphere annealing, the increase of the intensity of the (D0,X) peak and the disappearance of the (A0,X) peak in photoluminescence (PL) measurements suggested further that the crystal quality was improved. The detector performance was enhanced obviously after annealing. The higher the annealing temperature, the better the performance was. The detector fabricated by CMT:In slice (Cd atmosphere annealing at 1073 K for 240 h and Te atmosphere re-annealing at 773 K for 120 h) with 9.43% energy resolution and 1.25 × 10−3 cm2/V μτ value had the best detector performance.

The purpose of this study is to investigate the anti-angiogenic activities of NSK-01105, a novel sorafenib derivative, in in vitro, ex vivo and in vivo models, and explore the potential mechanisms. NSK-01105 significantly inhibited vascular endothelial growth factor (VEGF)-induced migration and tube formation of human umbilical vein endothelial cells at non-cytotoxic concentrations as shown by wound-healing, transwell migration and endothelial cell tube formation assays, respectively. Cell viability and invasion of LNCaP and PC-3 cells were significantly inhibited by cytotoxicity assay and matrigel invasion assay. Furthermore, NSK-01105 also inhibited ex vivo angiogenesis in matrigel plug assay. Western blot analysis showed that NSK-01105 down-regulated VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR2) and the activation of epidermal growth factor receptor (EGFR). Tumor volumes were significantly reduced by NSK-01105 at 60 mg/kg/day in both xenograft models. Immunohistochemical staining demonstrated a close association between inhibition of tumor growth and neovascularization. Collectively, our results suggest a role of NSK-01105 in treatment for human prostate tumors, and one of the potential mechanisms may be attributed to anti-angiogenic activities.

The present engineering practices show the potential that epoxy asphalt composites (EACs) would be a better choice to obtain long life for busy roads. To understand the service performance–related thermorheological properties of prepared bimodal anhydrides-cured rubber-like EACs (REACs), a direct tensile tester, dynamic shear rheometer and mathematical model were used. Tensile tests demonstrate that all the REACs reported here are more flexible than previously reported anhydrides-cured REACs at both 20 and 0 °C. The better flexibility is attributed to the change of bimodal networks, in which cross-linked short chains decreased and cross-linked long chains increased, relatively. Strain sweeps show that all the REACs have linear viscoelastic (LVE) properties when their strains are smaller than 1.0% from −35 to 120 °C. Temperature sweeps illustrate that the thermorheological properties of REACs evolve from thermosetting to quasi-thermosetting with asphalt content, and all the REACs retain solid state and show elastic properties in the experimental temperature range. A Cole–Cole plot and Black diagram indicate that all the REACs are thermorheologically simple materials, and the master curves were constructed and well-fitted by the Generalized Logistic Sigmoidal models. This research provides a facile approach to tune the thermorheological properties of the REACs, and the cheaper quasi-thermosetting REAC facilitates their advanced applications.

Background. Intervertebral disc degeneration (IDD) is a major cause of low back pain. Sinapine thiocyanate (ST) has been reported to have a wide range of biological activities. However, the treatment of IDD with ST has not been studied. Objectives. To explore the role and mechanism of ST treatment in IDD. Materials and methods. Nucleus pulposus cells (NPCs) were induced using lipopolysaccharide (LPS), which was used as an in vitro model of IDD. Cell activity, oxidative stress-related indicators and protein expression were detected using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, enzyme-linked immunosorbent assay (ELISA) and western blot. Pyroptosis was evaluated with propidium iodide (PI)/Hoechst double staining and immunofluorescence for NOD-like receptor protein 3 (NLRP3), and pyroptosis-related proteins and inflammatory factors were measured with western blot and ELISA. The pathological changes of IDD were assessed with hematoxylin & eosin (H&E) and safranin-O staining. Results. Our results showed that ST alleviated LPS-induced degeneration of NPCs, as evidenced by reducing reactive oxygen species (ROS), malondialdehyde (MDA), matrix metalloproteinase-13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and increasing collagen II and aggrecan expression. Moreover, ST repressed LPS-induced pyroptosis by inhibiting NLRP3, caspase-1 p20, interleukin (IL)-1β and IL-18. Further studies showed that ST did not restrain the activation of the JAK1/STAT3 signaling pathway induced by colivelin, or of the enhanced pyroptosis induced by polyphyllin VI. Sinapine thiocyanate alleviated IDD in vivo and suppressed NLRP3-mediated pyroptosis and the JAK1/STAT3 signaling pathway. Conclusions. Sinapine thiocyanate could alleviate IDD, although this did not include a reduction in NLRP3- mediated pyroptosis and inactivation of the JAK1/STAT3 signaling pathway, thus potentially being a candidate drug for IDD treatment. [ABSTRACT FROM AUTHOR]