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The indiscriminate use of antibiotics has resulted in a growing resistance to drugs in Pseudomonas aeruginosa. The identification of antibiotic resistance genes holds considerable clinical significance for prompt diagnosis. In this study, we established and optimized a Recombinase-Aided Amplification (RAA) assay to detect two genes associated with drug resistance, oprD and arr, in 101 clinically collected P. aeruginosa isolates. Through screening for the detection or absence of oprD and arr, the results showed that there were 52 Imipenem-resistant P. aeruginosa (IRPA) strains and 23 Rifampin-resistant P. aeruginosa (RRPA) strains. This method demonstrated excellent detection performance even when the sample concentration is 10 copies/μL at isothermal conditions and the results could be obtained within 20 minutes. The detection results were in accordance with the results of conventional PCR and Real-time PCR. The detection outcomes of the arr gene were consistently with the resistance spectrum. However, the antimicrobial susceptibility results revealed that 65 strains were resistant to imipenem, while 49 strains sensitive to imipenem with oprD were identified. This discrepancy could be attributed to genetic mutations. In summary, the RAA has higher sensitivity, shorter time, and lower-cost instrument requirements than traditional detection methods. In addition, to analyze the epidemiological characteristics of the aforementioned drug-resistant strains, we conducted Multilocus Sequence Typing (MLST), virulence gene, and antimicrobial susceptibility testing. MLST analysis showed a strong correlation between the sequence types ST-1639, ST-639, ST-184 and IRPA, while ST-261 was the main subtype of RRPA. It was observed that these drug-resistant strains all possess five or more virulence genes, among which exoS and exoU do not coexist, and they are all multidrug-resistant strains. The non-coexistence of exoU and exoS in P.aeruginosa is related to various factors including bacterial regulatory mechanisms and pathogenic mechanisms. This indicates that the relationship between the presence of virulence genes and the severity of patient infection is worthy of attention. In conclusion, we have developed a rapid and efficient RAA (Recombinase-Aided Amplification) detection method that offers significant advantages in terms of speed, simplicity, and cost-effectiveness (especially in time and equipment aspect). This novel approach is designed to meet the demands of clinical diagnostics.

Remote stimuli‐responsive movable soft robots without the need for complex 3D deformation processes and specific working environments is an unsolved problem and urgent need. In this work, under the inspiration of mother nature, a novel strategy of simple combination of the bionic bristles structure and the photothermal‐driven reversible shape change liquid crystal polymer (LCP) actuator is proposed to work out this difficulty. The combination structure is designed as unique three parts with two bionic bristle units at the two ends and one LCP unit in the center with a soft connection between them. After matching the driving force and the resistance, the prepared soft robot can realize the earthworm‐like unidirectionally crawl on the paper surface upon near‐infrared light irradiation through the contracting and stretching of LCP with a maximum average speed of 4.4 mm min−1. What's more, the crawling speed of the soft robot can be regulated by varying the irradiation distance of near‐infrared light or the length of the actuators. This strategy realizes the type of remote wireless control soft robot and has potential application ability in other soft robots with various demands.

Fruit locule number is an important agronomic trait that affects fruit appearance, quality, and yield. CLAVATA3 (SlCLV3) is a candidate gene of the fasciated (fas) locus that plays a role in controlling the number of flower organs and fruit locules in tomato. The SlCLV3 encoding signal peptide mainly acts by inhibiting the expression of WUSCHEL (WUS) but there is little research about how the receptor transmits the CLV3 signal to WUS and inhibits its expression. The CRISPR/Cas9 method was employed to edit the first exon of tomato SlCLV3 in this study, leading to the functional deletion of SlCLV3. As a result, flowers with a high number of organs and fruits with a high number of locules were produced. We screened six candidate genes using the transcriptome of clv3 mutants, analyzed expression variations in these genes between the cultivated allele and wild-type allele of fas, and showed that only SlLET6 and SlGIF1 (GRF1-interacting factor 1) were influenced by the fas locus. SlLET6 overexpression resulted in an increase in flower carpels and fruit locules. These results suggest that SlLET6 may be the downstream gene of SlCLV3 regulating the number of carpels and fruit locules in tomato.

Salmonella Typhimurium is a foodborne pathogen that causes gastrointestinal disease. This study aimed to screen probiotic strains to prevent S. Typhimurium infection and explore the corresponding mechanisms. Based on the excellent inhibitory effect, Lacticaseibacillus casei WLCA02 was selected and investigated for its potential protective mechanism against S. Typhimurium by different models, namely, the S. Typhimurium infection mice model, HT-29 epithelial cell model, and RAW264.7 macrophage model. Our results showed that supplementation of live and heat-killed WLCA02 could significantly reduce the Salmonella loads in mice, enhance the intestinal barrier via upregulating the expression of tight junction proteins (ZO-1 and Claudin-1) and the number of goblet cells, and alleviate the inflammation. Meanwhile, WLCA02 could reduce the internalization and mobility of S. Typhimurium, and activate the RAW264.7 macrophages and improve the inflammation caused by Salmonella. These results indicate that L. casei WLCA02 can potentially be developed as an antibacterial functional food.

Abstract The combination of Cartesian grid and the adaptive mesh refinement (AMR) technology is an effective way to handle complex geometry and solve complex flow problems. Some high-efficiency Cartesian-based AMR libraries have been developed to handle dynamic changes of the grid in parallel but still can not meet the unique requirements of simulating flow around objects. In this paper, we propose an efficient Cartesian grid generation method and an information transmission approach for the wall boundary to parallelize the implementation of ghost-cell method (GCM). Also, the multi-valued ghost-cell method to handle multi-value points is improved to adapt to the parallel framework. Combining the mentioned methodologies with the open-source library p4est, an automatic and efficient simulation of compressible flow is achieved. The overall performance of the methodology is tested through a wide range of inviscid/viscous flow cases. The results indicate that the capability and parallel scalability of the present numerical methodology for solving multiple types of flows, involving shock and vortices, multi-body flow and unsteady flows are agreeable as compared with related reference data.

This paper deals with a credit derivative pricing problem using the martingale approach. We generalize the conventional reduced-form credit risk model for a credit default swap market, assuming that the firms’ default intensities depend on the default states of counterparty firms and that the stochastic interest rate follows a jump-diffusion Cox–Ingersoll–Ross process. First, we derive the joint Laplace transform of the distribution of the vector process (rt,Rt) by applying piecewise deterministic Markov process theory and martingale theory. Then, using the joint Laplace transform, we obtain the explicit pricing of defaultable bonds and a credit default swap. Lastly, numerical examples are presented to illustrate the dynamic relationships between defaultable securities (defaultable bonds, credit default swap) and the maturity date.

This work deals with an optimal asset allocation problem for a defined contribution (DC) pension plan during its accumulation phase. The contribution rate is assumed to be proportional to the individual’s salary. The salary follows a Heston stochastic volatility model with jumps, and there exists common shock dependence between the salary and the volatility. Since the time horizon of pension management is quite long, the influence of inflation is considered in the given context. The aim of the pension plan described in this paper is to reduce fluctuations in terminal wealth by investing in the bond and the stock. Through the dynamic programming principle, the Hamilton–Jacobi–Bellman equation is shown. The explicit expression of the investment decision is derived by solving the Hamilton–Jacobi–Bellman equation. In the last part, a numerical analysis is shown to illustrate the impacts of different parameters on the optimal investment policy.

Sertoli cell-only syndrome (SCOS) is the most severe and common pathological type of non-obstructive azoospermia. The etiology of SCOS remains largely unknown to date despite a handful of studies reported in this area. According to the gene expression of testicular tissue samples in six datasets from the Gene Expression Omnibus, we detected 1441 differentially expressed genes (DEGs) between SCOS and obstructive azoospermia (OA) testicular tissue samples. Enriched GO terms and KEGG pathways for the downregulated genes included various terms and pathways related to cell cycle and reproduction, while the enrichment for the upregulated genes yielded many inflammation-related terms and pathways. In accordance with the protein-protein interaction (PPI) network, all genes in the most critical module belonged to the downregulated DEGs, and we obtained nine hub genes, including CCNB1, AURKA, CCNA2, BIRC5, TYMS, UBE2C, CDC20, TOP2A, and OIP5. Among these hub genes, six were also found in the most significant SCOS-specific module obtained from consensus module analysis. In addition, most of SCOS-specific modules did not have a consensus counterpart. Based on the downregulated genes, transcription factors (TFs) and kinases within the upstream regulatory network were predicted. Then, we compared the difference in infiltrating levels of immune cells between OA and SCOS samples and found a significantly higher degree of infiltration for most immune cells in SCOS than OA samples. Moreover, CD56bright natural killer cell was significantly associated with six hub genes. Enriched hallmark pathways in SCOS had remarkably more upregulated pathways than the downregulated ones. Collectively, we detected DEGs, significant modules, hub genes, upstream TFs and kinases, enriched downstream pathways, and infiltrated immune cells that might be specifically implicated in the pathogenesis of SCOS. These findings provide new insights into the pathogenesis of SCOS and fuel future advances in its theranostics.

Wind is one of the main factors raising errors in the spacecraft’s landing phase. As a result, an accurate description of incoming wind conditions is supposed to be a prerequisite for reliable parafoil trajectory planning. This work utilizes the Weather Research Forecast (WRF) model system with efficient parameterization schemes to reproduce the wind field in the main landing area during the landing phase of the “Shen Zhou” series spacecraft mission. In comparison with observational data from several cases, it is validated that the WRF model has the potential to give an accurate imitation of wind behaviors and is expected to be an alternative technique for costly and time-consuming experimental undertakings. Based on the numerical results, a linear model is proposed in the current work, which is applicable to the altitude range, specifically for parafoil trajectory planning. It is validated by comparisons with observational wind properties from radio-sounding stations. In addition, a sixth-order polynomial model is introduced for comparison as well. The results show that the current proposed model has both the characteristics of a simple form and good accuracy. It shows overall better consistency with observational data than the sixth-order polynomial model.

Hepatoblastoma (HB) is a rare disease but nevertheless the most common hepatic tumor in the pediatric population. For patients with advanced HB, the prognosis is dismal and there are limited therapeutic options. Multiple microRNAs (miRNAs) were reported to be involved in HB development, but the miRNA–mRNA interaction network in HB remains elusive. Through a comparison between HB and normal liver samples in the GSE131329 dataset, we detected 580 upregulated differentially expressed mRNAs (DE-mRNAs) and 790 downregulated DE-mRNAs. As for the GSE153089 dataset, the first cluster of differentially expressed miRNAs (DE-miRNAs) were detected between fetal-type tumor and normal liver groups, while the second cluster of DE-miRNAs were detected between embryonal-type tumor and normal liver groups. Through the intersection of these two clusters of DE-miRNAs, 33 upregulated hub miRNAs, and 12 downregulated hub miRNAs were obtained. Based on the respective hub miRNAs, the upstream transcription factors (TFs) were detected via TransmiR v2.0, while the downstream target genes were predicted via miRNet database. The intersection of target genes of respective hub miRNAs and corresponding DE-mRNAs contributed to 250 downregulated candidate genes and 202 upregulated candidate genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated the upregulated candidate genes mainly enriched in the terms and pathways relating to the cell cycle. We constructed protein–protein interaction (PPI) network, and obtained 211 node pairs for the downregulated candidate genes and 157 node pairs for the upregulated candidate genes. Cytoscape software was applied for visualizing the PPI network and respective top 10 hub genes were identified using CytoHubba. The expression values of hub genes in the PPI network were subsequently validated through Oncopression database followed by quantitative real-time polymerase chain reaction (qRT-PCR) in HB and matched normal liver tissues, resulting in six significant downregulated genes and seven significant upregulated genes. The miRNA–mRNA interaction network was finally constructed. In conclusion, we uncover various miRNAs, TFs, and hub genes as potential regulators in HB pathogenesis. Additionally, the miRNA–mRNA interaction network, PPI modules, and pathways may provide potential biomarkers for future HB theranostics.

Hepatoblastoma (HB) is the most common liver tumor in the pediatric population, with typically poor outcomes for advanced-stage or chemotherapy-refractory HB patients. The objective of this study was to identify genes involved in HB pathogenesis via microarray analysis and subsequent experimental validation. We identified 856 differentially expressed genes (DEGs) between HB and normal liver tissue based on two publicly available microarray datasets (GSE131329 and GSE75271) after data merging and batch effect correction. Protein–protein interaction (PPI) analysis and weighted gene co-expression network analysis (WGCNA) were conducted to explore HB-related critical modules and hub genes. Subsequently, Gene Ontology (GO) analysis was used to reveal critical biological functions in the initiation and progression of HB. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that genes involved in cell cycle phase transition and the PI3K/AKT signaling were associated with HB. The intersection of hub genes identified by both PPI and WGCNA analyses revealed five potential candidate genes. Based on receiver operating characteristic (ROC) curve analysis and reports in the literature, we selected CCNA2, CDK1, and CDC20 as key genes of interest to validate experimentally. CCNA2, CDK1, or CDC20 small interfering RNA (siRNA) knockdown inhibited aggressive biological properties of both HepG2 and HuH-6 cell lines in vitro. In conclusion, we identified CCNA2, CDK1, and CDC20 as new potential therapeutic biomarkers for HB, providing novel insights into important and viable targets in future HB treatment.

Hollow-core terahertz (THz) fibers have attracted a lot of research interest due to the low loss and easy inner modification with functional materials. Liquid water has unique properties in the THz region and has been widely investigated in THz emission, sensing, and devices. In this paper, a hollow-core THz Bragg fiber with a water defect layer is proposed. The finite element method is used to verify and analyze the tunable temperature characteristic of the water-filled THz fiber. The numerical analysis results show that the confinement loss and the low-frequency side of the dip near 0.5 THz can be controlled by the temperature of the liquid water. The temperature sensitivity of the THz fiber is obtained at 0.09614 dB·m−1/K at 0.45 THz with a high core power fraction up to 98%. The proposed THz fiber has potential applications in THz interaction with liquid and THz tunable devices.

To investigate the correlation of prostatic calculi (PC) with semen parameters in men with fertility intention, this retrospective case–control study enrolled 1,303 participants ranging from 20 to 59 years old; 725 were diagnosed with PC using abdominal ultrasonography. Patients with PC were classified into the type A calculi group (discrete and small echoes) and type B calculi group (coarse and large masses of multiple echoes). Five hundred and seventy-eight men without PC were recruited for the control group. The clinical data of each group were collected and analyzed. The total motility was significantly lower for subjects with type B calculi (41.84% ± 17.50%) than for subjects in the type A calculi (51.78% ± 20.84%; p < .001) and control (54.47% ± 20.74%; p < .001) groups. The percentage of progressively motile was significantly lower for the type B calculi (31.66% ± 14.68%) group than the type A calculi (40.17% ± 17.09%; p < .001) and control (41.83% ± 17.05%; p < .001) groups. The results of the hypo-osmotic swelling test yielded significantly lower percentages in the type B calculi group (59.88% ± 17.13%) than the type A calculi (65.28 ± 14.43%; p = .005) and control (66.92 ± 16.12%; p < .001) groups. The type B calculi group had a significantly higher percentage of round cell concentration than control (4.5% vs. 1.0%; p = .007) did. Small and discrete PC may not influence semen quality among adult men with fertility intention, but larger and coarser PC are associated with decreased sperm motility.

Time series analysis (TSA) based on multi-temporal polarimetric synthetic aperture radar (PolSAR) images can deeply mine the scattering characteristics of objects in different stages and improve the interpretation effect, or help to extract the range of surface changes. However, as far as classification is concerned, it is difficult to directly generate the classification map for a new temporal image, by the use of conventional TSA or change detection methods. Once some labeled samples exist in historical temporal images, semi-supervised domain adaptation (DA) is able to use historical label information to infer the categories of pixels in the new image, which is a potential solution to the above problem. In this paper, a novel semi-supervised DA algorithm is proposed, which inherits the merits of maximum margin criterion and principal component analysis in the DA learning scenario. Using a kernel mapping function established on the statistical distribution of PolSAR data, the proposed algorithm aims to find an optimal subspace for eliminating domain influence and keeping the key information of bi-temporal images. Experiments on both UAVSAR and Radarsat-2 multi-temporal datasets show that, superior classification results with the average accuracy of about 80% can be obtained by a simple classifier trained with historical labeled samples in the learned low- dimensional subspaces.

Dissolved organic matter (DOM) is one of the most reactive and mobile components in terrestrial ecosystems. Frequent loss of DOM has a negative effect on the surrounding environment. Current abundant deposition of atmospheric nitrogen (N) could significantly influence DOM leaching, and biochar has been suggested to be applied for improving acidic soils However, it remains unclear whether biochar affects dissolved organic carbon (DOC) or dissolved organic nitrogen (DON) loss induced by N deposition in acidic soils. In this study, we observed the effects of biochar amendment (BC0: 0 t biochar ha−1, BC20: 20 t biochar ha−1, and BC40: 40 t biochar ha−1) on the leaching of soil DOC and DON in Moso bamboo plantations that received simulated N deposition (N30: 30 kg N ha−1 yr−1, N60: 60 kg N ha−1 yr−1, N90: 90 kg N ha−1 yr−1, and N-free) for 34 months. DOC loss showed a marked seasonal variation with the lowest loss occurring in spring and the largest loss in summer; no such trend was observed in DON loss. Nitrogen deposition generally increased DOC and DON leaching loss in all four seasons, except DOC leaching loss in spring. Biochar amendment significantly decreased DOC leaching loss in spring, autumn, and winter; however, there was no significant effect on DON. Biochar may therefore mitigate DOC and DON loss caused by N deposition. DOC loss mitigation was also greater than that for DON, especially in autumn. Biochar application is a potential approach to mitigate the DOC and DON leaching loss induced by increasing atmospheric N deposition in Moso bamboo plantations. Keywords: Dissolved organic matter, Biochar, Simulated leaching, Simulated nitrogen deposition, Phyllostachys edulis

OBJECTIVE:Interpretation of diffusion MRI in the living brain requires validation against gold standard histological measures. We compared diffusion values of the nigrostriatal tract to PET and histological results in non-human primates (NHPs) with varying degrees of unilateral nigrostriatal injury induced by MPTP, a toxin selective for dopaminergic neurons. METHODS:Sixteen NHPs had MRI and PET scans of three different presynaptic radioligands and blinded video-based motor ratings before and after unilateral carotid artery infusion of variable doses of MPTP. Diffusion measures of connections between midbrain and striatum were calculated. Then animals were euthanized to quantify striatal dopamine concentration, stereologic measures of striatal tyrosine hydroxylase (TH) immunostained fiber density and unbiased stereologic counts of TH stained nigral cells. RESULTS:Diffusion measures correlated with MPTP dose, nigral TH-positive cell bodies and striatal TH-positive fiber density but did not correlate with in vitro nigrostriatal terminal field measures or in vivo PET measures of striatal uptake of presynaptic markers. Once nigral TH cell count loss exceeded 50% the stereologic terminal field measures reached a near zero floor effect but the diffusion measures continued to correlate with nigral cell counts. CONCLUSION:Diffusion measures in the nigrostriatal tract correlate with nigral dopamine neurons and striatal fiber density, but have the same relationship to terminal field measures as a previous report of striatal PET measures of presynaptic neurons. These diffusion measures have the potential to act as non-invasive index of the severity of nigrostriatal injury. Diffusion imaging of the nigrostriatal tract could potentially have diagnostic value in humans with Parkinson disease or related disorders.

The Reynolds-averaged Navier−Stokes (RANS)-based generalized actuator disc method along with the Reynolds stress model (AD/RANS_RSM) is assessed for wind turbine wake simulation. The evaluation is based on validations with four sets of experiments for four horizontal-axis wind turbines with different geometrical characteristics operating in a wide range of wind conditions. Additionally, sensitivity studies on inflow profiles (representing isotropic and anisotropic turbulence) for predicting wake effects are carried out. The focus is on the prediction of the evolution of wake flow in terms of wind velocity and turbulence intensity. Comparisons between the computational results and the measurements demonstrate that in the near and transition wake region with strong anisotropic turbulence, the AD/RANS_RSM methodology exhibits a reasonably good match with all the experimental data sets; however, in the far wake region that is characterized by isotropic turbulence, the AD/RANS_RSM predicts the wake velocity quite accurately but appears to over-estimate the wake turbulence level. While the introduction of the overall turbulence intensity is found to give an improved agreement with the experiments. The performed sensitivity study proves that the anisotropic inflow condition is recommended as the profile of choice to represent the incoming wind flow.

Apathy commonly occurs in Parkinson disease (PD) patients; however, the role of dopamine in the pathophysiology of apathy remains elusive. We previously demonstrated that dopaminergic dysfunction within the ventral tegmental area (VTA)-nucleus accumbens (NAcc) pathway contributes to the manifestation of apathetic behaviors in monkeys treated with the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We now extend these studies to identify dopaminergic dysfunction in cortical regions that correlate with development of apathetic behaviors. Specifically, we measured the effects of MPTP on monkeys' willingness to attempt goal directed behaviors, which is distinct from their ability to perform tasks. A total of 16 monkeys had baseline magnetic resonance imaging (MRI) and positron emission tomography (PET), using 6-[18F]fluorodopa (FD), [11C]dihydrotetrabenazine (DTBZ), and 2β-[11C]carbomethoxy-3β-(4-fluorophenyl)tropane (CFT). The monkeys received unilateral infusion of different doses of MPTP (0 - 0.31mg/kg) to produce a wide range of severity of motor parkinsonism. Eight weeks after MPTP, PET scans were repeated and animals were euthanized. Apathetic behavior and motor impairments were assessed blindly both pre- and post-MPTP infusion. Apathy scores were compared to in vitro and in vivo dopaminergic measures. Apathy scores increased following MPTP and correlated with PET measures of dopaminergic terminals (DTBZ or CFT) in dorsal lateral prefrontal cortex (DLPFC), ventromedial prefrontal cortex (VMPFC), and insular cortex (IC). Among all the cortical regions assessed, forward step-wise regression analyses indicated that only stereologic cell counts in VTA, and not counts in the substantia nigra (SN), predict dopamine transporter changes in IC. Our findings suggest that dopaminergic dysfunction within the VTA-IC pathway plays a role in the manifestation of apathetic behaviors in MPTP-lesioned primates.

Radioligands for DAT and VMAT2 are widely used presynaptic markers for assessing dopamine (DA) nerve terminals in Parkinson disease (PD). Previous in vivo imaging and postmortem studies suggest that these transporter sites may be regulated as the numbers of nigrostriatal neurons change in pathologic conditions. To investigate this issue, we used in vitro quantitative autoradioradiography to measure striatal DAT and VMAT2 specific binding in postmortem brain from 14 monkeys after unilateral internal carotid artery infusion of 1-Methyl-4-Phenyl-1,2,3,6-tetrahydropyridine (MPTP) with doses varying from 0 to 0.31 mg/kg. Quantitative estimates of the number of tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in substantia nigra (SN) were determined with unbiased stereology, and quantitative autoradiography was used to measure DAT and VMAT2 striatal specific binding. Striatal VMAT2 and DAT binding correlated with striatal DA (r(s) = 0.83, r(s) = 0.80, respectively, both with n = 14, p