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An efficient asymmetric and enantio-swithchable organocatalytic [3 + 3] annulation reaction using MBH-2-naphthoates of nitroalkenes and 4-hydroxyquinolin-2(1H)-ones has been developed. Densely substituted tetrahydropyrano[3,2-c]quinolinones scaffolds with two adjacent stereogenic centers are obtained with high yield (up to 95% yield) and good stereoselectivities (up to >20:1 dr and 96% ee) in an enantio-switchable manner. Furthermore, gram scale synthesis was achieved and the nitro group could easily transform into an amino group without any appreciable loss in the diastereo- and enantioselectivity.

Bulk samples of K doping K2xFeTe1-xSx with x = 0.07, 0.1, 0.2, 0.3 are successfully prepared by using easy-to-use stable compound K2S as the reactant. The lattice constant calculated from X-ray diffraction patterns indicate that K ions enter the Fe-Te-S layers. K doping is beneficial enhance the superconductivity transition temperature from the R-T curves. The apparent diamagnetic signal is observed in M-T curves when the content of K is smaller than 0.1. However, differential curves (dM/dT) in K-rich samples appear sharp slope mutations, which means that the Meissner effect signal is covered by the increased excess ferromagnetic ions. The number of excess Fe magnetic ions is proportional to K content, which may play an important role in determining the superconductivity.

To improve the ineluctable agglomeration and weak inherent conductivity of MgAl2O4 electrode materials, MgAl2O4/rGO composite is synthesized by a facile method and it shows large specific surface area and enhanced conductivity. Its particular framework can availably hold back the aggregation of MgAl2O4 and restacking of rGO, and accelerate reversible redox reactions. The MgAl2O4/rGO composite shows a specific capacity of 536.6 F/g at 1 A/g (257.3 F/g at 40 A/g) and retains 96.9% after 10,000 cycles at 5 A/g. An asymmetric supercapacitor is developed with MgAl2O4/rGO composite and activated carbon. An energy density of 16.2 Wh/kg is obtained at a power density of 400 kW/kg. Additionally, this device has successfully lighted up a LED, demonstrating its promising application in energy storage.

Comparative analyses are adopted to examine the influences of Cl− on the degradation of the film on Alloy 690TT in high-temperature water. According to the results of surface analyses and TEM, the composition and structure of the oxide film formed in a chloride solution are determined. Unlike the duplex layer oxide film formed on the sample in pure water, a thinner and monolayer Cr-rich oxide scale with several little corrosion pits on the surface is formed, which is closely related to the adsorption of Cl− ions due to their affinity to material surface and the selective dissolution of Ni-rich oxides.

The molecular of scaffold of thiazole orange has a number of merits for being as a fluorescent dye with tailor-made structure advancement for many useful applications. Structural modification based on 1-methylquinolinium moiety of thiazole orange is able to induce critical effects on fluorescent signal discrimination ability towards certain secondary or tertiary DNA structures. The electronic effect of the substituent on both molecular signaling and binding preference were investigated in the present study. We systematically compared the structural influence on the fluorescence signaling and binding preference towards nucleic acids in vitro through the addition of a number of substituent groups including p-methylstrylyl, p-hydroxylstyryl, p-chlorostyryl, p-bromostyryl, p-fluorostyryl, and (p-fluorobenzyl)-1,3-butadien-1-yl. The dyes synthesized were investigated with 19 nucleic acids for their interaction kinetics and fluorescent signal response with fluorescence titration experiments. The experimental results indicate that both the electronic effect and the molecular size of the dyes show significant influence on achieving higher binding affinity and fluorescent signal discrimination for G-quadruplex DNA. In addition, the dye with the introduction of a p-fluorostyryl substituent exhibits excellent linear relationship of the enhanced signal with respect to the concentration of telo21 DNA in vitro. The limit of detection (LOD) obtained was found to be 9 nM, which is much better than other analogues under the same conditions.

In this paper, artificial Intelligence (AI) algorithm is used in the Rietveld refinement process instead of the human decision. The program, PowderBot, is developed based on Fullprof engine, which proves the effectiveness of AI in Rietveld refinement. In this program, the decision making in refinement process is modelled as a Markov decision process (MDP), and solved by a reinforcement learning algorithm. PowderBot is designed to be a self-learning system capable of conducting structure refinement without human intervention. The program has already been successfully applied to Rietveld refinements. We hope this paper will encourage more Rietveld programs become more intelligent by the help of AI algorithm.

Single-cell RNA sequencing and transcriptome analysis enable novel discovery and precise characterization of new cell types and states, which improves the understanding of the cellular context of tumorigenesis. Herein, we applied this powerful approach to analyze 368 single cells from three esophageal squamous cell carcinoma (ESCC) and two esophageal adenocarcinoma (EAC) tumors. Using inferred copy number variation analysis, we successfully distinguished carcinoma cells from heterogeneous cellular populations, identifying gene signatures and crucial cancer-related signaling pathways related to ESCC and EAC. In particular, we found that NOTCH signaling was exclusively activated in ESCC, but not in EAC. ESCC tumors with higher NOTCH activity were associated with significantly worse survival rates than those with lower NOTCH activity. Collectively, this study revealed that ESCC and EAC are distinct in terms of cellular transcriptome profiles, which leads to a wide range of intratumoral cellular heterogeneity. The findings suggest that different therapeutic strategies that target the differences between two types of esophageal cancers are required, guiding cancer-specific future drug development.

New fluorescent dyes derivatized on a classical thiazole orange framework are able to show unexpectedly strong interaction signal and unusual binding selectivity with different structures of nucleic acid, particularly when bound with double-stranded DNA or G-quadruplex DNA. The present study reveals that these small binding ligands simply bearing an additional amino side group on its parent molecule of thiazole orange have almost no background fluorescence in solution. Conversely, they are able to produce an extremely strong yellow emission signal upon interaction with targeting nucleic acids in live cells. The induced fluorescence intensity was approximately 10–15 times stronger than that of thiazole orange. The dyes are therefore excellent fluorescent stains for bio-sensing and bio-imaging applications. It is particularly suitable for fluorescence microscopy experiments requiring very low working concentration (0.25 μM or less) targeting nucleic acids. This was demonstrated using pu27 G-quadruplex DNA, which has a low limit of detection (LOD = 3–4 nM) while thiazole orange was much higher (LOD = 48.7 nM) under the same conditions. In addition, it was found that structural modification on the quinolinium scaffold of thiazole orange was less effective than modification on the benzothiazole moiety. The findings of the present study provide important information for structural advancement of small molecules based on the widely used thiazole orange skeleton, resulting in analogues that are able to achieve higher sensitivity and selectivity for targeting at a specific class of nucleic acids. Computational docking studies were also conducted to illustrate the interaction behaviors of the dyes with different DNA structures.

Highlights • In this work a non-autonomous SIS network model is developed and analyzed. • The transmission rate is periodic to study impacts of the heterogeneity networks and seasonal diseases. • There exists a unique periodic solution which is globally asymptotically stable. • The heterogeneity is important in accelerating disease spreading and increasing the amplitude of solution., Seasonal forcing and contact patterns are two key features of many disease dynamics that generate periodic patterns. Both features have not been ascertained deeply in the previous works. In this work, we develop and analyze a non-autonomous degree-based mean field network model within a Susceptible-Infected-Susceptible (SIS) framework. We assume that the disease transmission rate being periodic to study synergistic impacts of the periodic transmission and the heterogeneity of the contact network on the infection threshold and dynamics for seasonal diseases. We demonstrate both analytically and numerically that (1) the disease free equilibrium point is globally asymptotically stable if the basic reproduction number is less than one; and (2) there exists a unique global periodic solution that both susceptible and infected individuals coexist if the basic reproduction number is larger than one. We apply our framework to Scale-free contact networks for the simulation. Our results show that heterogeneity in the contact networks plays an important role in accelerating disease spreading and increasing the amplitude of the periodic steady state solution. These results confirm the need to address factors that create periodic patterns and contact patterns in seasonal disease when making policies to control an outbreak.

The relationship between grain boundaries (GBs), carbides and stress corrosion cracking (SCC) of Alloy 690TT is investigated by immersion experiments using reverse U-bent specimens in a high temperature alkaline solution containing lead. The microstructures of blank samples and reverse U-bents are analyzed by scanning electron microscope with electron back scattering diffraction and transmission electron microscope. Detailed analyses indicate that Σ3 coherent twin boundaries are less susceptible to SCC than random high angle grain boundaries (RHGBs) due to the combined effect of carbides and GBs. A clear correlation and mechanism understanding relating GB character, carbide and susceptibility to SCC is established.

In this work, the hybrid nanostructures composed of Ni-Co hydroxide, reduced graphene oxide (rGO) and carbon nanotubes (CNTs) are successfully synthesized and used as a self-supported electrode for supercapacitors. It is found that the hybrid shows a big capacity of 1093 F g−1, excellent rate capability, and superior cycle life (100% capacity maintain after 5000 cycles). One asymmetric supercapacitor (ASC) is developed using Ni-Co hydroxide/rGO/CNTs as positive material and active carbon as negative material. This ASC displays a maximum energy density of 34.7 Wh kg−1 at a high power density of 1.55 kW kg−1 and still keeps 20.7 Wh kg−1 at 15.5 kW kg−1. Moreover, it displays remarkable cycle life with 112.8% capacity retention after 10000 cycles. Such asymmetric supercapacitor demonstrates great potential for practical application in energy storage devices.

Paclitaxel is widely used in the combination chemotherapy for many cancers including esophageal squamous cell carcinoma (ESCC). However, the paclitaxel resistance occurs frequently in treating ESCC and the mechanism is not fully understood yet. The heterogeneity of gene expression within the drug-resistant cancer cells may be one of the major factors contributing to its resistance. In the present study, we successfully induced paclitaxel resistance in ESCC cell line KYSE-30 through low dose and long-term treatment of paclitaxel. Gene expression profiles were measured utilizing population RNA-seq and single-cell RNA-seq (scRNA-seq). 37 single cells from KYSE-30 cells and 73 single cells from paclitaxel resistant KYSE-30 cells (Taxol-R) were subjected to scRNA-seq. Weighted gene co-expression network analysis (WGCNA) of scRNA-seq data revealed two major subpopulations in both KYSE-30 and Taxol-R cancer cells. Two subpopulations based on the KRT19 expression levels in KYSE-30 cells exhibited different paclitaxel sensitivity, suggesting the existence of an intrinsic paclitaxel resistance in KYSE-30 cells. In addition, the Taxol-R cells that acquired the resistance to paclitaxel through induction were characterized with higher expressions of proteasomes but a lower expression of HIF-1 signaling genes. Furthermore, we showed that carfilzomib (CFZ), a proteasome inhibitor, could attenuate the paclitaxel resistance in Taxol-R cancer cells through activating the HIF-1 signaling. Our new finding may pave a way leading to an improvement in the treatment on cancers including ESCC by combining CFZ with paclitaxel as a novel approach for cancer therapy.

Uniform MoS2 nanosheets assembling three-dimensional nanospheres are prepared by using a facile hydrothermal procedure with SiO2 nanospheres as the template. The morphologies and structure of MoS2 nanospheres are thorough characterized and evaluated as electrode material for supercapacitors. Galvanostatic charge/discharge measurements reveal that MoS2 nanospheres deliver a specific capacity of 683 F/g at 1 A/g, and the specific capacity retains about 85.1% after 10000 cycles. An aqueous asymmetric supercapacitor is fabricated by employing MoS2 nanospheres and activated carbon as the positive and negative electrodes, respectively. The specific capacitance is 65.33 F/g at a current density of 1 A/g. An energy density of 20.42 Wh/kg is obtained at power density of 750.31 kW/kg. The results show an attractive performance to take advantage of MoS2 nanosheets assembling three-dimensional nanospheres as electrode material for supercapacitors. Two cells in series can easily light the light-emitting diode lamp brightly, further demonstrates the high energy storage capability of the prepared MoS2 material.

The open reading frame 2 (ORF2) of Porcine circovirus type 2 (PCV2) encodes the major Capsid (Cap) protein, which self-assembles into virus-like particle (VLP) of similar morphology to the PCV2 virion and accumulates in the nucleus through the N-terminal arginine-rich nuclear localization signal (NLS). In this study, PCV2 Cap protein and its derivates were expressed via the baculovirus expression system, and the cellular localization of the recombinant proteins were investigated using anti-Cap mAb by imaging flow cytometry. Analysis of subcellular localization of Cap protein and its variants demonstrated that NLS mediated Cap protein nuclear export as well as nuclear import, and a phosphorylation site (S17) was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the NLS domain to regulate Cap protein nuclear export. Phosphorylation of NLS regulating the PCV2 Cap protein nuclear export was also demonstrated in PK15 cells by fluorescence microscopy. Moreover, the influence of Rep and Rep' protein on Cap protein subcellular localization was investigated in PK15 cells. Phosphorylation of NLS regulating Cap protein nuclear export provides more detailed knowledge of the PCV2 viral life cycle.

The chemical compositions, phases and structures of two oxide films on Alloy 690TT following exposure for 4400 h in pure water with and without lead at 320 °C were studied by surface analysis techniques. The analysis of a lead-doped oxide film prepared by a focused ion beam (FIB) demonstrated that both Cr-rich and Ni-rich oxides were alternatively distributed within the outer layer, whereas the inner layer was porous and poorly protected, causing severe corrosion of the alloy and a thicker film was formed. A duplex film model was proposed for the effects discussion of lead on the oxidation mechanism.

This study investigated the PbSCC of Alloy 690TT exposed to a caustic solution at 320 °C. Characterization of the resulting films indicates that lead is involved in the formation of oxides and evenly distributed in the films. TEM analysis was carried out to elucidate the role of lead in IGSCC by investigating the oxides at the crack tip. Lead penetrates into the crack tip and disperses in the intergranular oxides, enhancing the oxidation of grain boundaries. Thus, microcracks initiate within oxides under stress and connect with the main SCC crack stemming from the pit, resulting in propagation of the IGSCC.

Thiazole orange (TO) stains most nucleic acids giving strong fluorescence signal non-specifically. To resolve the poor discriminating ability of TO among tertiary structures of DNAs, a planar and rotatable π–conjugated small molecule designed by replacing the methylene bridge with an ethylene that slightly increases its structural flexibility, while maintain the crucial conjugated co-planar two-ring system. The study addressed the origin of signal discrimination for the molecule upon binding with different DNA structures and the results demonstrate that the molecule exhibits excellent fluorescence signal discrimination between the DNA G-quadruplexes and other DNA tertiary structures. In a typical staining assay, the molecule induced 30-fold greater fluorescence signal upon binding with Pu27 than that of ssDNA and dsDNA. Molecular modelling studies also support that the flexible ethylene bridge between the two-ring system is the crucial factor for inducing selectivity towards G-quadruplexes. Furthermore, the selectivity, sensitivity, and stability of the molecule were investigated with various techniques. The application of the molecule as a selective staining agent for imaging of G-quadruplex in human prostate cancer cells PC3 and mouse fibroblast L929 was also investigated. The strongly observed green fluorescence signal in the cell nucleus suggests that the molecule is able to enter into the nucleus and then binding with G-quadruplexes.

The latent period is one of the important risk factors considered in epidemiological research literatures. In general, a latent period can be modelled by incorporating a delay effect (delay system), or by introducing an exposed class defined as E. In this paper, a susceptible-vaccinated-exposed-infectious-pathogen (SVEIP) dynamic model and its corresponding delayed SVIP model are proposed. Under biologically motivated assumptions, the stability of equilibria is investigated by the global Lyapunov functions and functionals, and the dynamical properties of two systems are found to depend entirely on the basic reproduction numbers R 0 1 and R 0 2 : if R 0 1 ( R 0 2 ) ≤ 1 , the disease-free equilibrium is globally asymptotically stable; if R 0 1 ( R 0 2 ) > 1 , the endemic equilibrium exists and is globally asymptotically stable, which implies time delay span has no effect on the stability of equilibria in delay system. Finally, a comparison between SVEIP and delayed SVIP epidemic model is made by numerical analysis, elaborating the epidemiological significance of these results.

Anterior segment dysgenesis is often associated with cornea diseases, cataracts and glaucoma. The ciliary body (CB) is a part of the anterior segment that secretes aqueous and vitreous humor that nourishes the eye. Although defective Notch signaling in the CB disrupts CB morphogenesis and causes eye degeneration, the underlying mechanisms remain missing. Here, this study shows that NOTCH signaling controls CB morphogenesis by directly regulating Nectin1 expression, and maintains the vitreous and eye structures by regulating the expression of vitreous proteins and gap junction protein Cx43. Genetic inactivation of Rbpj or both Notch2 and Notch3 in the CB not only disrupts CB morphogenesis but also causes CB epithelial detachment and vitreous shrinkage in the developing eye, and eye degeneration in adults. Molecularly, NOTCH signaling transcriptionally controls the expression of adhesion protein Nectin1 known to be essential for CB morphogenesis, and controls eye pressure and the vitreous through stabilizing gap junction protein Cx43 known to be important for CB secretion. Mechanistically, Nectin1 directly binds and stabilizes Cx43. Finally, NOTCH signaling in the CB also directly controls the expression of vitreous proteins. Therefore, this study has provided important mechanistic insight into how NOTCH signaling controls CB morphogenesis and secretion, and also further suggests the potential involvement of CB secretion in various eye diseases, including retinal degeneration.

Aggregation is driven by both the size of the concentration and the city itself in the industry (urbanization). Since the new company to follow the existing companies in the same industry continues to cluster in these areas, the localized economy will create a cluster to produce the same product. The crisis of power shortage in the telecommunications industry in the summer of the peak power consumption period reduces the power cost through load management measures based on Neural Network (NN) using FPGA tool. Field of Business Intelligence (BI) is, by performing the direct mining data in the database, applying the power of data mining in a number of the hands of the business line and analysts. Sample of the customer, install the collect energy consumption data that the digital power meter. Effective load management strategies have been proposed; the load management measures’ contents can be summarized to compare the measured data. Result join the show's load management strategy, the telecommunications industry, and are very satisfied. In the margin adjustment and Time of Use (ToU) period, customers of this industry can save a certain amount of electricity.

Circulating tumor DNA (ctDNA) is becoming an important biomarker in noninvasive diagnosis and monitoring of tumor dynamics. This study tested the feasibility of plasma ctDNA for the non-invasive analysis of tumor mutations in esophageal squamous cell carcinoma (ESCC) by sequencing of tumor, tumor-adjacent, and normal tissue, as well as pre-surgery and post-surgery plasma. Exome sequencing of eight patients identified between 29 and 134 somatic mutations in ESCCs, many of which were also determined in ctDNA. Comparison of pre-surgery and post-surgery plasma has shown that mutations had reduced frequency or disappeared after surgery treatment. We further evaluated the TruSight Cancer sequencing panel by using it to detect mutations in the plasma of three patients. Tumor mutations were only found in one of them. To design a sequencing panel with improved targeting, we identified significantly mutated genes by meta-analysis of 532 ESCC genomes. Our results confirmed the well-known driver genes and found several uncharacterized genes. The new panel consisted of 90 recurrent genes, which theoretically achieved 94% and 75% of sensitivity when detecting at least 1 and 2 mutant genes in ESCC patients, respectively. Our results demonstrate the feasibility of using ctDNA to detect ESCCs and monitor treatment effect. The low-cost and sensitive target panel could facilitate clinical usage of ctDNA as a noninvasive biomarker.

In this paper, V2O5 was added into vitrified bond as a surfactant to improve the holding force of the vitrified bond to diamond abrasive and to improve the grinding performance of vitrified diamond grinding wheel. Results showed that the refractoriness of the vitrified bond with 4 wt% V2O5 reached 555 °C, 17 °C lower than that of the vitrified bond without V2O5. During sintering, vanadium ions in the bond was enriched on the diamond surface and combined with the unsaturated carbon atom existed on the surface of diamond to form V C bond, which can improve the wettability between vitrified bond and diamond abrasive; Li2Si2O5 phase began to precipitate in bond when addition of V2O5 content reached 2 wt%; The Flexural strength and Rockwell hardness were significantly improved from 83.7 MPa and 87.4 HRB to 112.6 MPa and 108.1 HRB, 34.5% and 23.7% higher than those of diamond composites without V2O5, respectively. The performance of the diamond grinding wheel prepared by adding 2 wt% V2O5 to the vitrified bond was improved, The roundness and straightness errors of the 50th zirconia workpiece in one dressing cycle decreased from 3.31 and 2.11 μm to 3.02 and 1.9 μm, respectively, as compared with the vitrified diamond wheel without V2O5.

Tumor heterogeneity and internal clonal evolution of human colorectal cancer stem cells (CRCSCs) within cancerous tissues often represents an aggressive feature of cancer progression. For a high-resolution examination of CRCSCs, we performed single cell whole-exome sequencing (scWES) of sorted cells, including three groups of CRCSCs: CD133+CD44+, CD133-CD44+, or CD133+CD44- cells, colorectal cancer cells (CRCCs) lacking these stem-cell markers (EpCAM+), plus one group of normal control cells. We examined and validated the scWES data for stem-specifically somatic alterations, clonal evolution, etc. Clonal evolution analysis showed that all CRCSCs were located at the main clone, and that the CD133+CD44- CRCSCs, which harbored the lowest number of mutations, were the likely origin of colorectal cancer (CRC) before evolving into other groups of CRCSCs/CRCCs. These results were validated by cell-lines culture experiments. Functional analyses validated that stem cell-specific mutated genes, such as GOLGA8J, ARHGAP39, LURAP1L, CDH1, were positively associated with stemness and knocking down each of them could increase the proportion of CD133+ cells. To validating mutations, especially stem cell-related genes, we performed targeted exome sequencing using a panel of all mutated genes to analyze the distribution of them in 96 samples (20 patients) those were also sorted into the same three groups of CRCSCs and CRCCs. We found two mutational sites of AHNAK2 gene (Chr14_105410531 and Chr14_105410533) were stem-cell specific in both scWES data and target sequencing data. PLIN4, HLA-B, ALK, CCDC92 and ALMS1 genes were specifically mutated in stem cells in both data. Another 33 genes tended to mutate in stem cells from all data. In all stem cell-related genes, AHNAK2, PTPRF and NIPPA5 which subcellularly located at plasma membrane had totally eleven predicted neoantigens. These neoantigens might be useful for some CRC patients in immunotherapy. All integrative analyses above suggested new markers for CRCSCs and showed the important roles of CRCSCs in tumorigenesis and progression of CRCs.

Animal diseases such as brucellosis and tuberculosis can be transmitted through an environmentally mediated mechanism, but the topics of most modeling work are based on infectious contact and direct transmission, which leads to the limited understanding of the transmission dynamics of these diseases. In this paper, we propose a new deterministic model which incorporates general incidences, various stages of infection and a general shedding rate of the pathogen to analyze the dynamics of these diseases. Under the biologically motivated assumptions, we derive the basic reproduction number R 0 , show the uniqueness of the endemic equilibrium, and prove the global asymptotically stability of the equilibria. Some specific examples are used to illustrate the utilization of our results. In addition, we elaborate the epidemiological significance of these results, which are very important for the prevention and control of animal diseases.

Construction and characterization of a full-length infectious clone (pMEV) of mink enteritis virus are described. Feline kidney cells (F81) were transfected with pMEV containing an engineered BamHI site that served as a genetic marker. The rescued virus was indistinguishable from its parental virus. The availability of a MEV infectious clone will facilitate studies of viral replication and pathogenicity and will permit the elucidation of determinants of the host range of the parvovirus.

In this study, uniform MoS2 nanosheets assembling three-dimensional (3D) nanospheres (MoS2 NPs) are developed via a facile hydrothermal procedure with silica (SiO2) nanospheres as a template. The MoS2 NPs catalyst exhibits high hydrogen evolution reaction (HER) performance with low onset overpotential of 87.0 mV, and small Tafel slope of 48.8 mV dec−1, which also exhibits excellent stability even after 30 h potential cycles. The superior HER activity is attributed to the unique 3D hierarchical structure, which provides enriched active edge sites and excellent electrical transport.

Brucellosis is one of the major zoonotic diseases in China, especially in Inner Mongolia where occurs the largest number of human brucellosis cases of Mainland China, which can be attributed to the large number of sheep kept there, since at least 90% of the human brucellosis cases are caused by sheep. Therefore, given the characteristics of the brucellosis infection in Inner Mongolia Autonomous Region, we propose a dynamic model for the sheep-human transmission of brucellosis, involving sheep population, human population and brucella in the environment. We first determine the basic reproduction number R 0 and analyze the global stability of the disease-free and endemic equilibrium. Secondly, using the reported human brucellosis data, we carry out numerical simulations and make sensitivity analysis of the basic reproduction number in terms of some parameters. The results show that brucellosis cannot be eradicated even though disinfection rate and vaccination rate of adult sheep are 100%. By investigating and comparing the effect of vaccination, disinfection and eliminating strategies, we find that vaccinating and disinfecting both young and adult sheep are appropriate and effective strategies to control brucellosis in Inner Mongolia of China.

A series of isaindigotone derivatives and analogues were designed, synthesized and evaluated as dual inhibitors of cholinesterases (ChEs) and self-induced β-amyloid (Aβ) aggregation. The synthetic compounds had IC50 values at micro or nano molar range for cholinesterase inhibition, and some compounds exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE, which were much better than the isaindigotone derivatives previously reported by our group. Most of these compounds showed higher self-induced Aβ aggregation inhibitory activity than a reference compound curcumin. The structure–activity relationship studies revealed that the derivatives with higher inhibition activity on AChE also showed higher selectivity for AChE over BuChE. Compound 6c exhibiting excellent inhibition for both AChE and self-induced Aβ aggregation was further studied using CD, EM, molecular docking and kinetics.

A series of quinolino-benzo-[5, 6]-dihydroisoquindolium compounds (3a, 3f, 3g, and 3j) derived from alkaloid berberine were designed and synthesized as novel G-quadruplex ligands. Subsequent biophysical and biochemical evaluation demonstrated that the addition of pyridine ring and amino group into berberine improved the binding ability and selectivity towards G-quadruplex DNA in comparison with the previously reported 9-N-substituted berberine derivatives. Furthermore, qRT-PCR assay showed compound 3j led the down-regulation of c-myc gene transcription in leukemia cell line HL60, while little effect on normal cell line ECV-304, which was consistent with the behavior of an effective G-quadruplex ligand targeting c-myc oncogene.

Quindoline derivatives as telomeric quadruplex ligands have shown good biological activity for telomerase inhibition. In the present study, we used spectroscopic and calorimetric methods to investigate the interactions between a quindoline derivative (5-methyl-11-(2-morpholinoethylamino)-10-H-indolo-[3,2-b]quinolin-5-ium iodide, compound 1) and human telomeric G-quadruplex. The thermodynamic studies using isothermal titration calorimetry (ITC) indicated that their binding process was temperature-dependent and enthalpy-entropy co-driven. The significant negative heat capacity was obtained experimentally from the temperature dependence of enthalpy changes, which was consistent with that from theoretical calculation, and all suggesting significant hydrophobic contribution to the molecular recognition process. Based on the results from UV-vis, ITC, steady-state and time-resolved fluorescence, their binding mode was determined as two ligand molecules stacking on the quartets on both ends of the quadruplex. These results shed light on rational design and development of quindoline derivatives as G-quadruplex binding ligands.

A series of new 9-O-substituted berberine derivatives (4a-j) as telomeric quadruplex ligands was synthesized and evaluated. The results from biophysical and biochemical assay indicated that introducing of positive charged aza-aromatic terminal group into the side chain of 9-position of berberine significantly improved the binding ability with G-quadruplex, and exhibited the inhibitory effect on the hybridization and on telomerase activity. These derivatives showed excellent selectivity for telomeric G-quadruplex DNA over duplex.

The E2 protein of Classical swine fever virus (CSFV) is an important envelope glycoprotein, which is responsible for inducing protective immune response in swine. Four antigenic domains, A–D, have been mapped on the E2 protein. The present study describes the identification of a linear B-cell epitope at the N-terminus of the E2 protein by screening a phage-displayed random 12-peptide library with the neutralizing monoclonal antibody (mAb) HQ06 directed against the E2 protein. HQ06 was found to bind to the phages displaying a consensus motif LFDGSNP, which is highly homologous to 772 LFDGTNP 778 of the CSFV polyprotein, locating on the border between antigenic domains B/C and A of the E2 protein. Considering that HQ06 showed reactivity with the motif 772 LFDGTNP 778 expressed as GST fusion in Western blot and indirect ELISA, we propose that the motif 772 LFDGTNP 778 represents a linear B-cell epitope of the E2 protein. The motif 773 FDGTNP 778 is the minimal requirement for the reactivity as demonstrated by analysis of the reactivity of HQ06 with several truncated peptides derived from the motif. Alignment of amino acid sequences from a number of CSFV isolates indicated that the epitope is well conserved among different subgroups of CSFV. Substitutions of the individual residues within the epitope 773 FDGTNP 778 demonstrated that residues 773 F, 775 G, and 778 P constitute the core of the epitope. The identified epitope will be useful for development of diagnostic assays and epitope-based marker vaccines against CSFV.

Based on calculations using density functional theory, we investigated the relative stabilities of the candidates for the most stable isomers of Sc3N@C79B, Sc3N@C79N, and Sc3N@C78BN. Judicious choices were applied to select stable isomers based on the electrostatic interaction between the Sc3N cluster and polar bonds of the cage. We predict that Sc3N@C80 can be doped with a boron atom or with a BN group substitutionally better than C60, suggesting that Sc3N@C79B and Sc3N@C78 BN could be produced in macroscopic amounts. As in the case of the substitution in Sc3N@C68, the feasibility of the B-substitution can be explained in terms of the electrostatic stabilization alone. However, we find that the BN-substitution is governed by a local preference complemented by the electrostatic effects. We also find that those substitutions restrict the rotation of the Sc3N cluster inside the cages to a certain degree, which is clearly different from the case of free rotation of the cluster in the undoped cage.

A thermokinetic model of hydrogen diffusion across a metallic tube is established. It includes the enthalpy change of the metal–hydrogen reaction, heat losses, dependences of reaction rate and hydrogen diffusion coefficient on temperature, and self-stress effects, etc. A phenomenon, the super fast diffusion of hydrogen before the up-hill diffusion and Fickian diffusion during hydrogen gas charging process, which has been found experimentally for 35 years, is presented by this model. Effects of pressures and other parameters are discussed.