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Individuals with cystic fibrosis (CF) often experience gastrointestinal (GI) abnormalities. In recent years, the intestinal microbiome has been postulated as a contributor to the development of CF-associated GI complications, hence representing a potential therapeutic target for treatment. We recently developed a rabbit model of CF, which is shown to manifest many human patient-like pathological changes, including intestinal obstruction. Here, we investigated the feces microbiome in young CF rabbits in the absence of antibiotics treatment. Stool samples were collected from seven- to nine-week-old CF rabbits (n = 7) and age-matched wild-type (WT) rabbits (n = 6). Microbiomes were investigated by iTag sequencing of 16S rRNA genes, and functional profiles were predicted using PICRUSt. Consistent with reports of those in pediatric CF patients, the fecal microbiomes of CF rabbits are of lower richness and diversity than that of WT rabbits, with a marked taxonomic and inferred functional dysbiosis. Our work identified a new CF animal model with the manifestation of intestinal dysbiosis phenotype. This model system may facilitate the research and development of novel treatments for CF-associated gastrointestinal diseases.

Abstract Psychological stress has been associated with intestinal epithelial hyperpermeability, the basic process in various functional and organic bowel diseases. In the present study, we aimed to clarify the differences and underlining mechanisms in stress-induced barrier disruption in functionally and structurally distinct epitheliums, including the villus epithelium (VE) and follicle-associated epithelium (FAE), a specialized epithelium overlaid the domes of Peyer’s lymphoid follicles. Employing an Ussing Chamber system, the epithelial permeability was assessed in rats following water avoidance stress (WAS) in vivo and in mucosa tissues exposed to corticotropin-releasing factor (CRF) ex vivo. Decreased transepithelial resistance (TER) and increased paracellular and transcellular macromolecular permeability in colon, ileal VE and FAE had been observed in WAS rats and in CRF-exposed mucosa. Especially, the barrier dysfunction was more serious in the FAE. Moreover, WAS upregulated the expression of mast cell tryptase and protease-activated receptor-2 (PAR2), which positively correlated with epithelial conductance. Mast cell stabilizer cromolyn sodium obviously alleviated the barrier disruption induced by WAS in vivo and CRF in vitro. Serine protease inhibitor aprotinin and FUT-175, and selective PAR2 antagonist ENMD-1068 effectively inhibited the CRF-induced FAE hyperpermeability. Altogether, it concluded that the FAE was more susceptible to stress, and the mast cells and PAR2 signaling played crucial roles in this process.

Metals: hydrogen probe divides nickel into grains Identifying all hydrogen absorption sites at metallic grain boundaries allows for a quantitative prediction of metal failure. An international team of researchers led by Ting Zhu at Georgia Institute of Technology developed a method to geometrically divide nickel metal into polyhedral packing units of atoms by embedding hydrogen atoms into the nickel atomic lattice. By using atomistic simulations to examine the boundaries through these atomic packing units, they showed that hydrogen binds to nickel via an electronic effect and that grain boundary failure due to hydrogen worsens at higher temperatures. Reducing grain boundary strength therefore depended on the location of hydrogen embedded in nickel as well as hydrogen concentration at the grain boundaries. Establishing a framework to quantify metal failure due to hydrogen absorption may help up mitigate failure in hydrogen-containing pressurized vessels and pipelines.

Abstract In general, photonic nanojets (PNJs) occur only when the refractive index (Ri) difference between the microparticle and background media is less than 2. The minimum full width at half-maximum (FWHM) of the PNJ is ~130 nm (approximately one-third of the illumination wavelength λ = 400 nm) formed within the evanescent field region. This paper proposes and studies a method to overstep the Ri upper bound and generate ultra-narrow PNJs. Finite element method based numerical investigations and ray-optics theoretical analyses have realized ultra-narrow PNJs with FWHM as small as 114.7 nm (0.287 λ) obtained from an edge-cut, length-reduced and parabolic-profiled microparticle with Ri = 2.5 beyond evanescent decay length. Using simple strain or compression operations, sub-diffraction-limited PNJs can be flexibly tuned on the order of several wavelengths. Such ultra-narrow PNJs offer great prospects for optical nonlinearity enhancements of greater enhancing effect, optical nanoscopy of higher spatial resolution, optical microprobes of smaller measurement accuracy, nano/micro-sized sample detections of higher sensing sensitivity, nanoscale objects of more accurate control, advanced manufactures of smaller processing size, optical-disk storage of larger data capacity and all-optical switching of lower energy consumption.

Abstract Self-standing photocatalytic membranes constructed from TiO2 nanofibers hold great promise in environmental remediation; however, challenges still remained for the poor mechanical properties of polycrystalline TiO2 nanofibers. Herein, soft Zr-doped TiO2 (TZ) nanofibrous membranes with robust mechanical properties and enhanced photocatalytic activity were fabricated via electrospinning technique. The Zr4+ incorporation could effectively inhibit the grain growth and reduce the surface defects and breaking point of TiO2 nanofiber. The as-prepared TZ membranes were composed of well-interconnected nanofibers with a high aspect ratios, small grain size and pore size, which exhibited good tensile strength (1.32 MPa) and showed no obvious damage after 200 cycles of bending to a radius of 2 mm. A plausible bending deformation mechanism of the soft TZ membranes was proposed from microscopic single nanofiber to macroscopical membranes. Moreover, the resultant TZ membranes displayed better photocatalytic performance for methylene blue degradation compared to a commercial catalyst (P25), including high degradation degree of 95.4% within 30 min, good reusability in 5 cycles, and easiness of recycling. The successful preparation of such fascinating materials may open up new avenues for the design and development of soft TiO2-based membranes for various application.

Abstract Combined phototherapy and immunotherapy demonstrates strong potential in the treatment of metastatic cancers. An upconversion nanoparticle (UCNP) based antigen‐capturing nanoplatform is designed to synergize phototherapies and immunotherapy. In particular, this nanoplatform is constructed via self‐assembly of DSPE‐PEG‐maleimide and indocyanine green (ICG) onto UCNPs, followed by loading of the photosensitizer rose bengal (RB). ICG significantly enhances the RB‐based photodynamic therapy efficiency of UCNP/ICG/RB‐mal upon activation by a near‐infrared (NIR) laser, simultaneously achieving selective photothermal therapy. Most importantly, tumor‐derived protein antigens, arising from phototherapy‐treated tumor cells, can be captured and retained in situ, due to the functionality of maleimide, which further enhance the tumor antigen uptake and presentation by antigen‐presenting cells. The synergized photothermal, photodynamic, and immunological effects using light‐activated UCNP/ICG/RB‐mal induces a tumor‐specific immune response. In the experiments, intratumoral administration of UCNP/ICG/RB‐mal, followed by noninvasive irradiation with an NIR laser, destroys primary tumors and inhibits untreated distant tumors, using a poorly immunogenic, highly metastatic 4T1 mammary tumor model. With the simultaneous use of anti‐CTLA‐4, about 84% of the treated tumor‐bearing mice achieve long‐term survival and 34% of mice develop tumor‐specific immunity. Overall, this antigen‐capturing nanoplatform provides a promising approach for the treatment of metastatic cancers.

Central fatigue is defined as a failure of the central nervous system to adequately drive the muscle, manifesting limited development, and maintenance of locomotor activity. A plateau in hypoxia leads to central fatigue and followed by maximal motility recession. However, the underlying mechanism is still unclear. The present study describes a mechanism by which liver CEBPβ (CCAAT/enhancer-binding protein beta) induced by hypoxic environment alters the kynurenine (KYN) metabolism and causes the suppression of motility function recession. The activation of CEBPβ under hypoxia increases the liver expression of tryptophan dioxygenase, thereby enhancing the conversion of tryptophan into KYN; the KYN metabolite can traverse the blood-brain barrier and result in the suppression of motility function. However, the knockdown of CEBPβ by injecting pAAV-shRNA-CEBPβ via the hepatic portal vein reduces the KYN production and improves the motility function. KYN is a neurochemical that which restricts the exercise capacity after injection in the basal ganglia in mice. Reducing the plasma KYN protects the brain from hypoxia-induced changes associated with fatigue, and the knockdown liver of CEBPβ in mice renders resistance to fatigue post-acute hypoxia or tryptophan treatment. This study reveals resistance to central fatigue as a strategy for acclimatization to hypoxia mediated by transcription factor CEBPβ in the liver.

Highly conductive and stable electrode materials are usually the focus of high-performance supercapacitors. In this work, a unique design of Ni2P@carbon self-supported composite nanowires directly grown on Ni foam was applied for a supercapacitor. The Co3O4 nanowire array was first synthesized on the Ni foam substrate, and the resulting Ni2P@carbon nanocomposite was obtained by hydrothermally coating Co3O4 with the Ni-ethylene glycol complex followed by gaseous phosphorization. We have discovered that the molecular weight of surfactant polyvinylpyrrolidone (PVP) used in the hydrothermal step, as well as the temperature for phosphorization, played very important roles in determining the electrochemical properties of the samples. Specifically, the sample synthesized using PVP with 10 k molecular weight and phosphorized at 300°C demonstrated the best supercapacitive performance among the different samples, with the highest capacitance and most stable cyclic retention. When an asymmetric supercapacitor (ASC) was assembled with this Ni2P@carbon sample as the cathode and activated carbon (AC) as the anode, the ASC device showed excellent capacitances of 3.7 and 1.6 F cm-2 at 2 and 50 mA cm-2, respectively, and it kept a high capacitance of 1.2 F cm-2 after 5000 cycles at a current rate of 25 mA cm-2. In addition, the ASC could reach a high energy density of about 122.8 Wh kg-1 at a power density of 0.15 kW kg-1 and 53.3 Wh kg-1 at the highest power density of 3.78 kW kg-1. Additionally, this device also had the ability to power up 16 red LEDs effortlessly, making it a strong candidate in electrochemical energy storage for practical usage.

Neurotensin is a peptide hormone released from enteroendocrine cells in the small intestine in response to fat ingestion. Although the mechanisms regulating neurotensin secretion are still incompletely understood, our recent findings implicate a role for extracellular signal-regulated kinase 1 and 2 as positive regulators of free fatty acid-stimulated neurotensin secretion. Previous studies have shown that kinase suppressor of Ras 1 acts as a molecular scaffold of the Raf/MEK/extracellular signal-regulated kinase 1 and 2 kinase cascade and regulates intensity and duration of extracellular signal-regulated kinase 1 and 2 signaling. Here, we demonstrate that inhibition of kinase suppressor of Ras 1 attenuates neurotensin secretion and extracellular signal-regulated kinase 1 and 2 signaling in human endocrine cells. Conversely, we show that overexpression of kinase suppressor of Ras 1 enhances neurotensin secretion and extracellular signal-regulated kinase 1 and 2 signaling. We also show that inhibition of extracellular signal-regulated kinase 2 and exocyst complex component 70, a substrate of extracellular signal-regulated kinase 2 and mediator of secretory vesicle exocytosis, potently inhibits basal and docosahexaenoic acid-stimulated neurotensin secretion, whereas overexpression of exocyst complex component 70 enhances basal and docosahexaenoic acid-stimulated neurotensin secretion. Together, our findings demonstrate a role for kinase suppressor of Ras 1 as a positive regulator of neurotensin secretion from human endocrine cells and indicate that this effect is mediated by the extracellular signal-regulated kinase 1 and 2 signaling pathway. Moreover, we reveal a novel role for exocyst complex component 70 in regulation of neurotensin vesicle exocytosis through its interaction with the extracellular signal-regulated kinase 1 and 2 signaling pathway.

Shenfu Tang and Dushen Tang (one of the composite medicines for Shenfu Tang) are widely used Traditional Chinese herbal formulations and ginsenosides are their main bioactive components. However, there are rare studies about simultaneous analysis of ginsenosides in Shenfu Tang and Dushen Tang. In order to identify ginsenosides in Shenfu Tang and Dushen Tang and to explore law of compatibility of medicines in the decoction, a method for simultaneous determination of twelve ginsenosides in Shenfu Tang and Dushen Tang was developed by ultraresolution liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The method showed satisfactory linearity (r > 0.9915), repeatability (RSD < 9.58%), intra- and interday precisions (RSD

Light trapping in single nanowires (NWs) is of vital importance for photovoltaic applications. However, circular NWs (CNWs) can limit their light-trapping ability due to high geometrical symmetry. In this work, we present a detailed study of light trapping in single silicon NWs with an elliptical cross-section (ENWs). We demonstrate that the ENWs exhibit significantly enhanced light trapping compared with the CNWs, which can be ascribed to the symmetry-broken structure that can orthogonalize the direction of light illumination and the leaky mode resonances (LMRs). That is, the elliptical cross-section can simultaneously increase the light path length by increasing the vertical axis and reshape the LMR modes by decreasing the horizontal axis. We found that the light absorption can be engineered via tuning the horizontal and vertical axes, the photocurrent is significantly enhanced by 374.0% (150.3%, 74.1%) or 146.1% (61.0%, 35.3%) in comparison with that of the CNWs with the same diameter as the horizontal axis of 100 (200, 400) nm or the vertical axis of 1000 nm, respectively. This work advances our understanding of how to improve light trapping based on the symmetry breaking from the CNWs to ENWs and provides a rational way for designing high-efficiency single NW photovoltaic devices.

Production of immunodeficient (ID) models in non-murine animal species had been extremely challenging until the advent of gene-editing tools: first zinc finger nuclease (ZFN), then transcription activator-like effector nuclease (TALEN), and most recently clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR)/Cas9. We and others used those gene-editing tools to develop ID rabbits carrying a loss of function mutation in essential immune genes, such as forkhead box protein N1 (FOXN1), recombination activating gene 1/2 (RAG1/2), and interleukin 2 receptor subunit gamma (IL2RG). Like their mouse counterparts, ID rabbits have profound defects in their immune system and are prone to bacterial and pneumocystis infections without prophylactic antibiotics. In addition to their use as preclinical models for primary immunodeficient diseases, ID rabbits are expected to contribute significantly to regenerative medicine and cancer research, where they serve as recipients for allo- and xeno-grafts, with notable advantages over mouse models, including a longer lifespan and a much larger body size. Here we provide a concise review of the history and current status of the development of ID rabbits, as well as future perspectives of this new member in the animal model family.

CRISPR/Cas9 and transcription activator-like effector nuclease (TALEN) are becoming major tools for genome editing. Here, Song et al. show that RS-1, a small-molecule enhancer for homology directed repair, increases the CRISPR/Cas9 and TALEN mediated knock-in efficiency both in vitro and in vivowith rabbit.

This study theoretically proposed a novel surface plasmon resonance biosensor by incorporating emerging two dimensional material blue phosphorus and graphene layers with plasmonic gold film. The excellent performances employed for biosensing can be realized by accurately tuning the thickness of gold film and the number of blue phosphorus interlayer. Our proposed plasmonic biosensor architecture designed by phase modulation is much superior to angular modulation, providing 4 orders of magnitude sensitivity enhancement. In addition, the optimized stacked configuration is 42 nm Au film/2-layer blue phosphorus /4-layer graphene, which can produce the sharpest differential phase of 176.7661 degrees and darkest minimum reflectivity as low as 5.3787 × 10−6. For a tiny variation in local refractive index of 0.0012 RIU (RIU, refractive index unit) due to the binding interactions of aromatic biomolecules, our proposed biosensor can provide an ultrahigh detection sensitivity up to 1.4731 × 105 °/RIU, highly promising for performing ultrasensitive biosensing application.

River meanders form complex 3D flow patterns, including secondary flows and flow separation. In particular, the flow separation traps solutes and delays their transport via storage effects associated with recirculating flows. The simulation of the separated flows highly relies in the performance of turbulence models. Thus, these closure schemes can control dispersion behaviors simulated in rivers. This study performs 3D simulations to quantify the impact of the turbulence models on solute transport simulations in channels under different sinuosity conditions. The 3D Reynolds-averaged Navier-Stokes equations coupled with the k − ε , k − ω and SST k − ω models are adopted for flow simulations. The 3D Lagrangian particle-tracking model simulates solute transport. An increase in sinuosity causes strong transverse gradients of mean velocity, thereby driving the onset of the separated flow recirculation along the outer bank. Here, the onset and extent of the flow separation are strongly influenced by the turbulence models. The k − ε model fails to reproduce the flow separation or underestimates its size. As a result, the k − ε model yields residence times shorter than those of other models. In contrast, the SST k − ω model exhibits a strong tailing of breakthrough curves by generating more pronounced flow separation.

Terahertz pulsed imaging (TPI) was introduced approximately fifteen years ago and has attracted a lot of interest in the pharmaceutical industry as a fast, non-destructive modality for quantifying film coatings on pharmaceutical dosage forms. In this topical review, we look back at the use of TPI for analysing pharmaceutical film coatings, highlighting the main contributions made and outlining the key challenges ahead.

Development of nanoparticles with multi-functionalities is of great importance. In this study, praseodymium sulfide (Pr _2 S _3 ) and molybdenum sulfide (MoS _2 ) nanoparticles were synthesized. The structural, morphological and optical properties of the as-obtained products were investigated by XRD, XPS, TEM, UV–vis-NIR spectroscopy, and photoluminescence spectroscopy. Pr _2 S _3 is found to be used in selective photodegradation of fluorescein sodium salt. MoS _2 can be utilized for selective photodegradation of rhodamine B. In the mixture of rhodamine B, fluorescein sodium salt and rhodamine 6 G, most of rhodamine B and part of fluorescein sodium salt are optically degraded by Pr _2 S _3 . In the mixture of rhodamine B, fluorescein sodium salt and rhodamine 6 G, part of fluorescein sodium salt and most of rhodamine B is degraded by MoS _2 . Moreover, they emit near-infrared fluorescence (800–1100 nm) when excited by the 785 nm light. Deep tissues imaging with high-contrast is shown, utilizing a nanoparticle-filled centrifuge tube covered with animal tissues (pig Bacon meat). Maximum imaging depth below the tissue surface of 1 cm is achieved. Our work provides a rapid yet efficient procedure to make nanoparticles for dual-application-potential in dye-photodegradation and near-infrared deep tissue imaging.

Timely and accurately identification of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can greatly contribute to monitoring and controlling the global pandemic. This study gained theoretical insight into a novel phase-modulation plasmonic biosensor working in the near-infrared (NIR) regime, which can be employed for sensitive detection of SARS-CoV-2 and its spike (S) glycoprotein. The proposed plasmonic biosensor was created by integrating two-dimensional (2D) Van der Waals heterostructures, including tellurene and carboxyl-functionalized molybdenum disulfide (MoS _2 ) layers, with transparent indium tin oxide (ITO) film. Excellent biosensing performance can be achieved under the excitation of 1550 nm by optimizing the thickness of ITO film and tellurene-MoS _2 heterostructures. For a sensing interface refractive index change as low as 0.0012 RIU (RIU, refractive index unit), the optimized plasmonic configuration of 121 nm ITO film/three-layer tellurene/ten-layer MoS _2 -COOH can produce the highest detection sensitivity of 8.4069 × 10 ^4 degree/RIU. More importantly, MoS _2 –COOH layer can capture angiotensin-converting enzyme II, which is an ideal adsorption site for specifically binding SARS-CoV-2 S glycoprotein. Then, an excellent linear detection range for S glycoprotein and SARS-CoV-2 specimens is ∼0–301.67 nM and ∼0–67.8762 nM, respectively. This study thus offers an alternative strategy for rapidly performing novel coronavirus diagnosis in clinical applications.

Mammalian telomere lengths are primarily regulated by telomerase, a ribonucleoprotein consisting of a reverse transcriptase (TERT) and an RNA subunit (TERC). TERC is constitutively expressed in all cells, whereas TERT expression is temporally and spatially regulated, such that in most adult somatic cells, TERT is inactivated and telomerase activity is undetectable. Most tumor cells activate TERT as a mechanism for preventing progressive telomere attrition to achieve proliferative immortality. Therefore, inactivating TERT has been considered to be a promising means of cancer therapy. Here we applied the CRISPR/Cas9 gene editing system to target the TERT gene in cancer cells. We report that disruption of TERT severely compromises cancer cell survival in vitro and in vivo. Haploinsufficiency of TERT in tumor cells is sufficient to result in telomere attrition and growth retardation in vitro. In vivo, TERT haploinsufficient tumor cells failed to form xenograft after transplantation to nude mice. Our work demonstrates that gene editing-mediated TERT knockout is a potential therapeutic option for treating cancer.

Using the CRISPR/Cas9 gene-editing technology, we recently produced a number of rabbits with mutations in immune function genes, including FOXN1, PRKDC, RAG1, RAG2, and IL2RG. Seven founder knockout rabbits (F0) and three male IL2RG null (−/y) F1 animals demonstrated severe combined immunodeficiency (SCID), characterized by absence or pronounced hypoplasia of the thymus and splenic white pulp, and absence of immature and mature T and B-lymphocytes in peripheral blood. Complete blood count analysis showed severe leukopenia and lymphocytopenia accompanied by severe neutrophilia. Without prophylactic antibiotics, the SCID rabbits universally succumbed to lung infections following weaning. Pathology examination revealed severe heterophilic bronchopneumonia caused by Bordetella bronchiseptica in several animals, but a consistent feature of lung lesions in all animals was a severe interstitial pneumonia caused by Pneumocystis oryctolagi, as confirmed by histological examination and PCR analysis of Pneumocystis genes. The results of this study suggest that these SCID rabbits could serve as a useful model for human SCID to investigate the disease pathogenesis and the development of gene and drug therapies.

Background and challenges to implementation Tobacco use is the leading preventable cause of morbidity and mortality worldwide, yet the usage rate continues to increase in low- and middle-income countries such as China.Of over 310 million smokers lives in China, which accounts for 27.7% of the general population. Intervention or response In 2014, the BI collaborated with the Chinese Center for Health Education to implement the national tobacco control mass media campaign in China. The campaign was expected to improve knowledge about health effects of smoking and SHS exposure and shape attitudes and behaviors toward tobacco control policies. The campaign was adapted from materials which depicts a office environment with SHS to show how it affects everyone. It was broadcast on the national Television channels and six provincial satellite networks, meanwile on social media and mini-site for a four-week period. Results and lessons learnt To evaluate the effectiveness of this campaign, a total of 2400 participants were selected to complete interviews through a stratified random sampling. The participants consisted of 828(34.5%) smokers, and 1,572(65.5%) nonsmokers. The campaign reached about 24% of the Chinese population and increased smokers' knowledge about the harmful effects of SHS exposure(73% vs. 85%, p< 0.05). Both smokers and nonsmokers increased their knowledge that smoking lead to diseases other than lung cancer. Although smokers exposed to the campaign were more likely to take actions to reduce smoking than those not exposed(13% vs. 7%, p< 0.05), the percentage was still low. The support for bans on smoking in public places increased after the campaign, especially among nonsmokers and females. However, the support for ban on smoking in bars(48%) and restaurants(62%) were lower than that in hospitals(95%) and schools(94%). Conclusions and key recommendations The mass media campaign reinforced people's knowledge and attitudes about harmful health effects of smoking and SHS exposure, increased people's desire to quit, and improved people's support for smoking bans in public places.

The apple ( × Borkh.) is an economically and culturally important crop grown worldwide. Growers of this long-lived perennial must produce fruit of adequate quality while also combatting abiotic and biotic stress. Traditional apple breeding can take up to 20 yr from initial cross to commercial release, but genomics-assisted breeding can help accelerate this process. To advance genomics-assisted breeding in apple, we performed genome-wide association studies (GWAS) and genomic prediction in a collection of 172 apple accessions by linking over 55,000 single nucleotide polymorphisms (SNPs) with 10 phenotypes collected over 2 yr. Genome-wide association studies revealed several known loci for skin color, harvest date and firmness at harvest. Several significant GWAS associations were detected for resistance to a major fungal pathogen, apple scab ( [Cke.] Wint.), but we demonstrate that these hits likely represent a single ancestral source. Using genomic prediction, we show that most phenotypes are sufficiently predictable using genome-wide SNPs to be candidates for genomic selection. Finally, we detect a signal for firmness retention after storage on chromosome 10 and show that it may not stem from variation in , a gene repeatedly identified in bi-parental mapping studies and widely believed to underlie a major QTL for firmness on chromosome 10. We provide evidence that this major QTL is more likely due to variation in a neighboring ethylene response factor (ERF) gene. The present study showcases the superior mapping resolution of GWAS compared to bi-parental linkage mapping by identifying a novel candidate gene underlying a well-studied, major QTL involved in apple firmness.

Maize stalk rot is a major fungal disease worldwide, and is difficult to control by chemical methods. Therefore, in maize breeding, quantitative trait loci (QTLs) conferring resistance are important for controlling the disease. Next-generation sequencing technologies are considered a rapid and efficient method to establish the association of agronomic traits with molecular markers or candidate genes. In the present study, we employed QTL-seq, which is a whole-genome resequencing-based approach, to identify candidate genomic regions conferring resistance to maize stalk rot. A novel resistance QTL Rgsr8.1 was finely mapped, conferring broad-spectrum resistance to Gibberella stalk rot (GSR). Segregation analysis in F2 and BC1F1 populations, which were derived from a cross between 18327 (Susceptible) and S72356 (Resistant), indicated that the resistance to GSR was likely to be a quantitatively inherited trait in maize. The result of QTL-seq showed that the resistance to GSR was mapped on chromosome 8 from 161.001 to 170.6 Mb. Based on the simple sequence repeat (SSR) markers, single-nucleotide polymorphism (SNP) markers, and the recombinant test, the location of Rgsr8.1 was narrowed down to 2.04 Mb, flanked by SSR-65 and SNP-25 markers at the physical location from 164.69 to 166.72 Mb based on the maize reference genome. In this region, two candidate resistant genes were found with, one auxin-responsive elements and the other encoding a disease resistance protein. In summary, these results will be useful in maize breeding programs to improve the resistance to GSR in maize.

We propose a novel design to enhance third harmonic generation (THG) using individual Au nanorods (NRs) coated with gain materials. The present design avoids the use of conventional gap systems, where complicated semiconductor techniques must be used in order to realize the corresponding high-resolution planar structures. As such, this design can contribute to a significant THG enhancement from nanoparticles; this THG is especially favorable for many applications (e.g, photovoltaic devices, bioimaging, and therapy). We perform numerical simulations using a finite-difference time domain (FDTD) in order to identify the origin of the enhanced nonlinear response based on the present system. In addition, we present an effective method to characterize the third harmonics by using Fourier analysis separating them from the excited light. The results show that the THG enhancement of the gain-assisted Au NR with a critical gain coefficient is one to two orders of magnitude greater than the highest values reported for gap THG systems.

Single-molecule surface-enhanced Raman scattering (SERS) has been extensively studied over the past decade. In this paper, we propose a novel method to obtain ultrahigh enhancement of local electric fields by using a silver nanoshell with a gain core above a silver substrate. Numerical results show that an ultrahigh enhancement factor of the local electric field on the order of 105-106 and a SERS enhancement factor on the order of 1020-1025 can be obtained with the present system. The SERS enhancement factor is five orders of magnitude greater than the highest theoretical value reported for SERS applications at the single-molecule level. In addition, we use the finite-element method to analyze in detail the influences of the gain coefficient of the gain core and the other structure parameters on the enhancement factor.

A wireless sensor network is a network consisting of wireless sensor nodes. There are usually requirements that need to be met when deploying a wireless sensor network, one being the placement of nodes. Due to placement requirements and limited node transmission range, a network might be partitioned initially. Therefore, additional relay nodes are added to the network to form an interconnected network. In this article, the minimum relay nodes placement problem in wireless sensor networks is addressed. This problem addresses the placement of relay nodes: the minimum number needed and where the nodes should be placed. The problem is formulated as a Steiner tree problem with minimum Steiner points and a bounded edge length problem, which is NP-hard. In this article, we present a variable-dimension meta-heuristic based on particle swarm optimization called multi-space particle swarm optimization to address the problem. We tested multi-space particle swarm optimization using randomly generated instances of the Steiner tree problem with minimum Steiner points and a bounded edge length problem of varying sizes and found that multi-space particle swarm optimization is effective in addressing the Steiner tree problem with minimum Steiner points and a bounded edge length problem.

The purpose of this retrospective study is to evaluate the diagnostic value of contrast enhanced sonography plus gastric distention sonography, the Double Contrast-enhanced Ultrasound (DCUS) in gastric lesions.107 cases with pathology confirmed gastric lesions were retrospectively reviewed, DCUS and oral contrast agent ultrasound (US) were performed in all cases prior to operation. Perfusion parameters including arrival time (AT), peak intensity (PI), time to peak (TTP), and area under the curve (AUC) of the lesion and surrounding normal tissue were analyzed. A reader blinded to pathology results were asked to rate and compare each case with surgical or resection biopsy pathology results.From the 107 gastric lesions, 75 were malignant gastric lesions (33 gastric cancers,42 gastrointestinal stromal tumors (GISTs)) and 32 were benign gastric lesions (11 inflammatory masses and 21 polypoid adenomas). Compared with US, DCUS achieved higher value in sensitivity (90.6% vs. 70.6%), specificity (75% vs. 62.5%), positive predictive value (89.5% vs. 81.5%), negative predictive value (77.4% vs. 47.6%), and overall accuracy (85.9% vs. 68.2%). When US was tested against DCUS, the increase in correct diagnoses value was significant (P = .01). Furthermore, gastric cancer had faster AT, higher PI and AUC than normal tissue (P

The ubiquitination pathway regulates growth, development, and stress responses in plants, and the U-box protein family of ubiquitin ligases has important roles in this pathway. Here, 64 putative U-box proteins were identified in the Medicago truncatula genome. In addition to the conserved U-box motif, other functional domains, such as the ARM, kinase, KAP, and WD40 domains, were also detected. Phylogenetic analysis of the M. truncatula U-box proteins grouped them into six subfamilies, and chromosomal mapping and synteny analyses indicated that tandem and segmental duplications may have contributed to the expansion and evolution of the U-box gene family in this species. Using RNA-seq data from M. truncatula seedlings subjected to three different abiotic stresses, we identified 33 stress-inducible plant U-box genes (MtPUBs). Specifically, 25 salinity-, 15 drought-, and 16 cold-regulated MtPUBs were detected. Among them, MtPUB10, MtPUB17, MtPUB18, MtPUB35, MtPUB42, and MtPUB44 responded to all three stress conditions. Expression profiling by qRT-PCR was consistent with the RNA-seq data, and stress-related elements were identified in the promoter regions. The present findings strongly indicate that U-box proteins play critical roles in abiotic stress response in M. truncatula.

Aim. In this study, we aimed to investigate the effects of febuxostat, a novel inhibitor of xanthine oxidase (XO), on renal damage in streptozotocin- (STZ-) induced diabetic rats. Methods. Diabetes was induced by the intraperitoneal injection of STZ in male Sprague-Dawley rats. Sham-injected rats served as controls. The control and diabetic rats were treated with and without febuxostat for 8 weeks, respectively. Fasting blood and 24-h urine samples were collected every 4 weeks. Rat livers were extracted for detecting gene expression, content, and bioactivity of XO. Results. Diabetic rats showed significantly increased serum uric acid (SUA), serum creatinine (SCr), and urea nitrogen (BUN) levels. Daily urinary albumin (UAE), uric acid (UUA), and creatinine (UCr) excretion were also significantly increased in these rats. In diabetic rats, at week 8, febuxostat decreased SUA by 18.9%, while UAA was increased by 52.0%. However, UCr and urinary urea nitrogen (UUN) levels remained unchanged, while SCr and BUN levels decreased by >30% in these rats. Although hepatic gene expression, content, and activity of XO increased significantly in diabetic rats, febuxostat only slightly decreased its content. Conclusions. Febuxostat significantly attenuated renal damage in STZ-induced diabetic rats in addition to exerting hypouricemic effect.

To investigate the effects of four strains, generally used in clinic, including Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis, and their related products on human colonic smooth muscle in vitro.Human colonic circular muscle strips obtained from disease-free margins of resected segments from 25 patients with colorectal cancer were isometrically examined in a constant-temperature organ bath and exposed to different concentrations of living bacteria, sonicated cell fractions and cell-free supernatant (CFS). The area under the curve (AUC) representing the contractility of smooth muscle strips was calculated.(1) The four living probiotics inhibited the contractility of human colonic muscle strips only at high concentration (1010 CFUs/mL, all P0.05).Four common probiotics related products, including the sonicated cell fractions and the CFS, obviously inhibited human colonic smooth muscles strips contraction in a dose-dependent manner. Only high concentration living probiotics (1010 CFUs/mL) can inhibit the colonic smooth muscles strips contraction. The NO pathway may be partly involved in the inhibitory effect of CFS from Streptococcus thermophilus and Enterococcus faecalis.

Intraspecific hybridization between Triticum petropavlovskyi Udacz. et Migusch., synthetic hexaploid wheat (SHW-DPW), and tetraploid and hexaploid wheat, was performed to collect data on seed set, fertility of F1 hybrid, and meiotic pairing configuration, aiming to evaluate the possible origin of T. petropavlovskyi. Our data showed that (1) seed set of crosses T. petropavlovskyi × T. polonicum and T. petropavlovskyi × T. aestivum cv. Chinese Spring was significantly high; (2) fertility of hybrids T. petropavlovskyi × T. polonicum and T. petropavlovskyi × T. aestivum ssp. yunnanense was higher than that of the other hybrids; (3) fertility of F1 hybrids SHW-DPW × T. dicoccoides and SHW-DPW×T. aestivum ssp. tibetanum was significantly high; and (4) c-value of T. petropavlovskyi × T. polonicum and T. petropavlovskyi × T. aestivum cv. Changning white wheat was also significantly high. The results indicate that the probable origin of T. petropavlovskyi is divergence from a natural cross between T. aestivum and T. polonicum, via either spontaneous introgression or breeding effort.

Fouling is a great problem that significantly affects the continuous operation for large-scale radio-frequency (RF) thermal plasma synthesizing nanopowders. In order to eliminate or weaken the phenomenon, numerical simulations based on FLUENT software were founded to investigate the effect of operation parameters, including feeding style of central gas and sheath gas, on plasma torches. It is shown that the tangential feeding style of central gas brings serious negative axial velocity regions, which always forces the synthesized nanopowders to “back-mix”, and further leads to the fouling of the quartz tube. Moreover, it is shown that sheath gas should be tangentially fed into the plasma reactor to further eliminate the gas stream’s back-mixing. However, when this feeding style is applied, although the negative axial velocity region is decreased, the plasma gas and kinetic energy of the vapor phase near the wall of the plasma reactor are less and lower, respectively; as a result, that plasma flame is more difficult to be arced. A new plasma arcing method by way of feeding gun instead of torch wall was proposed and put in use. The fouling problem has been well solved and plasma arcing is well ensured, and as a result, the experiment on large-scale production of nanopowders can be carried out for 8 h without any interruption, and synthesized Si and Al2O3 nanopowders exhibit good dispersion and sphericity.

Graphene, with high biocompatibility, physiological solubility and stability, has been reported as an emerging material for biomedical applications such as biosensors, drug delivery, and tissue engineering. Recently, identifying the technological competition (TC) of graphene biomedical technology has received worldwide attention from stakeholders. However, few studies have attached great importance to review the TC of this field by the analysis of patents. The main objective of this study is to develop a new and comprehensive method to investigate TC in a given technology field by conducting a patent review and then employing a patent roadmap to dig out the technology opportunity. The effectiveness of the approach is verified with the case study on graphene biomedical technology. Compared to previous research, this study makes the following important contributions. First, this study provides a new and systematic framework for the dynamic analysis of TC in a given technology field. It also extends the research perspectives of TC for industry, assignees, and technology, employs a patent roadmap to dig out technology opportunities, and enables stakeholders to understand TC from a dynamic perspective. Second, this study integrates patent analysis with a patent roadmap that has not appeared in existing methodologies of patent review. Third, it first introduces indicators (e.g., high value patent and competition position of top assignees) to the previous patent roadmap and provides a new methodology for patent roadmaps from a country level and assignee level. Finally, this study provides useful information for stakeholders interested in graphene biomedical technology, helps them to find new technology opportunities in this field, encourages them to determine the direction of future research, and has important significance for its application to diverse other emerging technologies.

Metallic nanocrystals exhibit superior properties to their bulk counterparts because of the reduced sizes, diverse morphologies, and controllable exposed crystal facets. Therefore, the fabrication of metal nanocrystals and the adjustment of their properties for different applications have attracted wide attention. One of the typical examples is the fabrication of nanocrystals encased with high-index facets, and research on their magnified catalytic activities and selections. Great accomplishment has been achieved within the field of noble metals such as Pd, Pt, Ag, and Au. However, it remains challenging in the fabrication of base metal nanocrystals such as Ni, Cu, and Co with various structures, shapes, and sizes. In this paper, the synthesis of metal nanocrystals is reviewed. An introduction is briefly given to the metal nanocrystals and the importance of synthesis, and then commonly used synthesis methods for metallic nanocrystals are summarized, followed by specific examples of metal nanocrystals including noble metals, alloys, and base metals. The synthesis of base metal nanocrystals is far from satisfactory compared to the tremendous success achieved in noble metals. Afterwards, we present a discussion on specific synthesis methods suitable for base metals, including seed-mediated growth, ligand control, oriented attachment, chemical etching, and Oswald ripening, based on the comprehensive consideration of thermodynamics, kinetics, and physical restrictions. At the end, conclusions are drawn through the prospect of the future development direction.

Since maize is one of the most important cereal crops in the world, establishment of an efficient genetic transformation system is critical for its improvement. In the current study, several elite corn lines were tested for suitability of Agrobacterium tumefaciens-mediated transformation by using immature embryos as explants. Infection ability and efficiency of transformation of A. tumefaciens sp. strains EHA105 and LBA4404, different heat treatment times of immature embryos before infection, influence of L-cysteine addition in co-cultivation medium after transformation, and how different ways of selection and cultivation influence the efficiency of transformation were compared. Glyphosate-resistant gene 2mG2-EPSPS was transformed into several typical maize genotypes including 78599, Zong 31 and BA, under the optimum conditions. Results showed that the hypervirulent Agrobacterium tumefaciens sp. strain EHA105 was more infectious than LBA4404. Inclusion of L-cysteine (100 mg L−1) in co-cultivation medium, and heating of the immature embryos for 3 min prior to infection led to a significant increase in the transformation efficiency. Growth in resting medium for 4-10 d and delaying selection was beneficial to the survival of resistant calli. During induction of germination, adding a high concentration of 6-BA (5 mg L−1) and a low concentration of 2,4-D (0.2 mg L−1) to regeneration medium significantly enhanced germination percentage. Using the optimized transformation procedure, more than 800 transgenic plants were obtained from 78599, Zong 31 and BA. By spraying herbicide glyphosate on leaves of transgenic lines, we identified 66 primary glyphosate-resistant plants. The transformation efficiency was 8.2%. PCR and Southern-blot analyses confirmed the integration of the transgenes in the maize genome.

The complete mitochondrial genome of the intertidal barnacle Tetraclita rufotincta Pilsbry, 1916 (Crustacea: Maxillopoda: Sessilia) is presented. The genome is a circular molecule of 15,236 bp, which encodes a set of 37 typical metazoan mitochondrial genes. All non-coding regions are 438 bp in length, with the longest one speculated as the control region (242 bp), which is located between srRNA and trnK. Comparison of the genome and those of three other species from Tetraclitidae shows that gene arrangement is identical, indicating that the mitochondrial gene order is highly conserved in the family. Moreover, in comparison with the pancrustacean ground pattern, the four species of Tetraclitidae share three large conserved gene blocks. Phylogenetic analysis based on 13 mitochondrial PCGs shows that Chelonbia testudinaria (Coronulidae) clusters with the four species of Tetraclitidae. Within Tetraclitidae, T. serrata clusters with T. japonica, and the two grouped with T. rufotincta with high support (BP = 100), with T. divisa as the most distantly related species (BP = 100).

Objective. To investigate changes in the glycated hemoglobin A1c (A1c) level and those in β cell function and insulin resistance in newly diagnosed and drug naive type 2 diabetes patients and to evaluate the relationship between them. Design and Methods. A total of 818 newly diagnosed diabetic individuals who were ≥40 years of age were recruited. The subjects were grouped by A1c values (

Betatrophin and irisin are two recently identified hormones which may participate in regulating pancreatic β-cell function. However, the associations of these two hormones with β-cell function remain unclear. The present study aims to demonstrate the associations of circulating betatrophin and irisin levels with β-cell function, assessed by the area under the curve (AUC) of C-peptide, and the possible correlation between these two hormones in previously diagnosed type 2 diabetes mellitus (T2DM) patients. In total, 20 age-, sex-, and body mass index- (BMI-) matched normal glucose tolerance (NGT) subjects and 120 previously diagnosed T2DM patients were included in this study. Partial correlation analysis was used to evaluate the relationships between these two hormones and indexes of β-cell function and insulin resistance. Our results showed that betatrophin levels were significantly elevated, while irisin levels were significantly decreased, in patients with T2DM compared with NGT subjects. However, partial correlation analysis showed that betatrophin levels did not correlate with β-cell function-related variables or insulin resistance-related variables before or after controlling multiple covariates, while irisin correlated positively with insulin sensitivity but is not associated with β-cell function-related variables. Besides, no correlation was observed between betatrophin and irisin levels. Hence we concluded that betatrophin and irisin were not associated with β-cell function in previously diagnosed T2DM patients.

In VANET (vehicular ad hoc network) environment, the successive vehicle position data actually are discrete, so the key to the moving vehicle modeling is to effectively reduce the updating frequency of the position data so as to alleviate the communication and database management load. This paper proposes vehicle position data updating strategy with packet repetition based on Kalman filter predicting. Firstly, we design a position data updating model based on Kalman filter difference predicting equations. Then, we design a packet repetition mode decision algorithm, which is applied to deliver vehicle position updating data. The model with packet repetition can not only generate position updating data according to preset threshold, but also decide packet repetition mode related to the distance of two adjacent vehicles in order to reduce data loss. Both simulated highway and realistic urban road experimental results show that vehicle position data updating frequency could be obviously reduced and the reliability of the communication is greatly improved through packet repetition mechanism by using this position updating strategy.

Density functional theory (DFT) calculations and ab-initio molecular dynamics (AIMD) simulations were performed to understand graphene and its interaction with polycyclic aromatic hydrocarbons (PAHs) molecules. The adsorption energy was predicted to increase with the number of aromatic rings in the adsorbates, and linearly correlate with the hydrophobicity of PAHs. Additionally, the analysis of the electronic properties showed that PAHs behave as mild n-dopants and introduce electrons into graphene; but do not remarkably modify the band gap of graphene, indicating that the interaction between PAHs and graphene is physisorption. We have also discovered highly sensitive strain dependence on the adsorption strength of PAHs onto graphene surface. The AIMD simulation indicated that a sensitive and fast adsorption process of PAHs can be achieved by choosing graphene as the adsorbent. These findings are anticipated to shed light on the future development of graphene-based materials with potential applications in the capture and removal of persistent aromatic pollutants.

Fruit and seed development in plants is a complex biological process mainly involved in input and biosynthesis of many storage compounds such as proteins and oils. Although the basic biochemical pathways for production of the storage metabolites in plants are well characterized, their regulatory mechanisms are not fully understood. In this study, we functionally identified rapeseed (Brassica napus) miR394 with its target gene Brassica napus leaf curling responsiveness (BnLCR) to dissect a role of miR394 during the fruit and seed development. Transgenic rapeseed plants over-expressing miR394 under the control of the cauliflower mosaic virus 35S promoter were generated. miR394 over-expression plants exhibited a delayed flowering time and enlarged size of plants, leaf blade, pods and seed body, but developed seeds with higher contents of protein and glucosinolates (GLS) and lower levels of oil accumulation as compared to wild-type. Over-expression of miR394 altered the fatty acid (FA) composition by increasing several FA species such as C16:0 and C18:0 and unsaturated species of C20:1 and C22:1 but lowering C18:3. This change was accompanied by induction of genes coding for transcription factors of FA synthesis including leafy cotyledon1 (BnLEC1), BnLEC2, and FUSCA3 (FUS3). Because the phytohormone auxin plays a crucial role in fruit development and seed patterning, the DR5-GUS reporter was used for monitoring the auxin response in Arabidopsis siliques and demonstrated that the DR5 gene was strongly expressed. These results suggest that BnmiR394 is involved in rapeseed fruit and seed development.