Estimating the Quality of Reprogrammed Cells Using ES Cell Differentiation Expression Patterns

Somatic cells can be reprogrammed to a pluripotent state by over-expression of defined factors, and pluripotency has been confirmed by the tetraploid complementation assay. However, especially in human cells, estimating the quality of Induced Pluripotent Stem Cell(iPSC) is still difficult. Here, we present a novel supervised method for the assessment of the quality of iPSCs by estimating the gene expression profile using a 2-D “Differentiation-index coordinate”, which consists of two “developing lines” that reflects the directions of ES cell differentiation and the changes of cell states during differentiation. By applying a novel liner model to describe the differentiation trajectory, we transformed the ES cell differentiation time-course expression profiles to linear “developing lines”; and use these lines to construct the 2-D “Differentiation-index coordinate” of mouse and human. We compared the published gene expression profiles of iPSCs, ESCs and fibroblasts in mouse and human “Differentiation-index coordinate”. Moreover, we defined the Distance index to indicate the qualities of iPS cells, which based on the projection distance of iPSCs-ESCs and iPSCs-fibroblasts. The results indicated that the “Differentiation-index coordinate” can distinguish differentiation states of the different cells types. Furthermore, by applying this method to the analysis of expression profiles in the tetraploid complementation assay, we showed that the Distance index which reflected spatial distributions correlated the pluripotency of iPSCs. We also analyzed the significantly changed gene sets of “developing lines”. The results suggest that the method presented here is not only suitable for the estimation of the quality of iPS cells based on expression profiles, but also is a new approach to analyze time-resolved experimental data

Photoluminescence from Bi5(GaCl4)3 molecular crystal

Bi5(GaCl4)3 sample has been synthesized through the oxidation of Bi metal by gallium chloride (GaCl3) salt. Powder X-ray diffraction as well as micro-Raman scattering results revealed that, in addition to crystalline Bi5(GaCl4)3 in the product, amorphous phase containing [GaCl4]- and [Ga2Cl7]- units also exist. The thorough comparison of steady-state and time-resolved photoluminescent behaviors between Bi5(GaCl4)3 product and Bi5(AlCl4)3 crystal leads us to conclude that Bi53+ is the dominant emitter in the product, which gives rise to the ultrabroad emission ranging from 1 to 2.7 micrometer. Detailed quantum chemistry calculation helps us assign the observed excitations to some electronic transitions of Bi53+ polycation, especially at shorter wavelengths. It is believed that our work shown here not only is helpful to solve the confusions on the luminescent origin of bismuth in other material systems, but also serves to develop novel broadband tunable laser materials

Immunogenicity and Protective Capacity of Sugar ABC Transporter Substrate-Binding Protein against Streptococcus suis Serotype 2, 7 and 9 Infection in Mice

Background: Streptococcus suis (S. suis) is a Gram-positive bacterium that causes substantial disease in pigs. S. suis is also an emerging zoonoses in humans, primarily in Asia, through the consumption of undercooked pork and the handling of infected pig meat as well as carcasses. The complexity of S. suis epidemiology, characterized by the presence of multiple bacterial serotypes and strains with diverse sequence types, identifies a critical need for a universal vaccine with the ability to confer cross-protective immunity. Highly conserved immunogenic proteins are generally considered good candidate antigens for subunit universal vaccines. Methods: In this study, the cross-protection of the sugar ABC transporter substrate-binding protein (S-ABC), a surface-associated immunogenic protein of S. suis, was examined in mice for evaluation as a universal vaccine candidate. Results: S-ABC was shown to be highly conserved, with 97% amino acid sequence identity across 31 S. suis strains deposited in GenBank. Recombinantly expressed S-ABC (rS-ABC) was recognized via rabbit sera specific to S. suis serotype 2. The immunization of mice with rS-ABC induced antigen-specific antibody responses, as well as IFN-γ and IL-4, in multiple organs, including the lungs. rS-ABC immunization conferred high (87.5% and 100%) protection against challenges with S. suis serotypes 2 and 9, demonstrating high cross-protection against these serotypes. Protection, albeit lower (50%), was also observed in mice challenged with S. suis serotype 7. Conclusions: These data identify S-ABC as a promising antigenic target within a universal subunit vaccine against S. suis

Characterization and Genomic Analysis of SFPH2, a Novel T7virus Infecting Shigella

Shigellosis, caused by Shigella, is a major global health concern, with nearly 164.7 million cases and over a million deaths occurring annually worldwide. Shigella flexneri is one of the most common subgroups of Shigella with a high incidence of multidrug-resistance. The phage therapy approach is an effective method for controlling multidrug-resistant bacteria. However, only a few Shigella phages have been described to date. In this study, a novel lytic bacteriophage SFPH2 was isolated from a sewage sample obtained from a hospital in Beijing, China, using a multidrug-resistant S. flexneri 2a strain (SF2) isolated from the fecal sample of a dysentery patient. SFPH2 is a member of the Podoviridae virus family with an icosahedral capsid and a short, non-contractile tail. It was found to be stable over a wide range of temperatures (4–50°C) and pH values (pH 3–11). Moreover, SFPH2 could infect two other S. flexneri serotypes (serotypes 2 variant and Y). High-throughput sequencing revealed that SFPH2 has a linear double-stranded DNA genome of 40,387 bp with 50 open reading frames. No tRNA genes were identified in the genome. Comparative analysis of the genome revealed that the SFPH2 belongs to the subfamily Autographivirinae and genus T7virus. The genome shows high similarity with other enterobacterial T7virus bacteriophages such as Citrobacter phage SH4 (95% identity and 89% coverage) and Cronobacter phage Dev2 (94% identity and 92% coverage). A comparison of the fiber proteins showed that minor differences in the amino acid residues might specify different protein binding regions and determine host species. In conclusion, this is the first report of a T7virus that can infect Shigella; SFPH2 has a functional stability under a wide range of temperatures and pH values, showing the potential to be widely applied to control Shigella–associated clinical infections and reduce the transmission rates of S. flexneri serotype 2a and its variants in the environment

Silicon and oxygen synergistic effects for the discovery of new high-performance nonfullerene acceptors

In organic electronics, an aromatic fused ring is a basic unit that provides -electrons to construct semiconductors and governs the device performance. The main challenge in developing new pi -skeletons for tuning the material properties is the limitation of the available chemical approach. Herein, we successfully synthesize two pentacyclic siloxy-bridged pi -conjugated isomers to investigate the synergistic effects of Si and O atoms on the geometric and electronic influence of pi -units in organic electronics. Notably, the synthesis routes for both isomers possess several advantages over the previous approaches for delivering conventional aromatic fused-rings, such as environmentally benign tin-free synthesis and few synthetic steps. To explore their potential application as photovoltaic materials, two isomeric acceptor-donor-acceptor type acceptors based on these two isomers were developed, showing a decent device efficiency of 10%, which indicates the great potential of this SiO-bridged ladder-type unit for the development of new high-performance semiconductor materials.Developing a new pi -skeletal aromatic fused-ring for tuning material properties in organic electronics is still a challenge due to limited chemical approach. Here, the authors enrich the chemistry by synthesizing SiO-bridged ladder-type pi -skeletons with enhanced planarity and deeper energy levels than CO-bridged counterpart

Effects of Acute Exercise on Cognitive Flexibility in Young Adults with Different Levels of Aerobic Fitness

This study aimed to evaluate the effects of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) on cognitive flexibility in young adults with differing levels of aerobic fitness. Sixty-six young adults were grouped into high- and low-fit groups based on their final running distance on the 20 m Progressive Aerobic Cardiovascular Endurance Run (PACER) test. Individuals participated in a 10 min HIIE, a 20 min HIIE, a 20 min MICE, and a control session (reading quietly in a chair) in a counterbalanced order. The more-odd shifting task was completed before and approximately 5 min after each intervention to assess cognitive flexibility. The results showed that young adults with a high fitness level gained greater benefits in terms of switch cost from the 20 min HIIE, while low-fitness participants benefited more from the 10 min HIIE and the 20 min MICE. These findings suggest that aerobic fitness may influence the effect of acute HIIE and MICE on cognitive flexibility. Young adults should consider individual fitness level when adopting time-effective and appropriate exercise routines to improve cognitive flexibility

TiO2 surface modification and characterization with nanosized PbS in dye-sensitized solar cells

The nanoporous TiO2 films utilized in dye-sensitized solar cells (DSSCs) possess a large surface-to-volume ratio, which facilitates the adsorption of sensitizing dye and the recombination due to the high density of surface traps. In this paper, nanosized PbS was fabricated on the TiO 2 films. The components of the modified TiO2 film were studied by X-ray diffraction (XRD) and electron probe microanalysis (EPMA), while the structure of the film was characterized with BET physisorption and high-resolution scanning electron microscopy (HRSEM). The results showed that the PbS particles were 2-3 nm and discrete on the surface of TiO2. Diffusion photovoltage (PV) spectroscopy was employed to study the charge separation and diffusion processes inside modified and unmodified TiO 2 films. The diffusion PV signals revealed that the traps on the surface of TiO2 were extremely reduced due to the presence of PbS. The results of transient photovoltage and back I-V characteristics showed that the back reaction, that is, the recombination due to the reaction between an electron on TiO2 and the hole-transporting media, was retarded significantly. © 2006 American Chemical Society

Adaptive phase I-II clinical trial designs identifying optimal biological doses for targeted agents and immunotherapies

Targeted agents and immunotherapies have revolutionized cancer treatment, offering promising options for various cancer types. Unlike traditional therapies the principle of "more is better" is not always applicable to these new therapies due to their unique biomedical mechanisms. As a result, various phase I-II clinical trial designs have been proposed to identify the optimal biological dose that maximizes the therapeutic effect of targeted therapies and immunotherapies by jointly monitoring both efficacy and toxicity outcomes. This review article examines several innovative phase I-II clinical trial designs that utilize accumulated efficacy and toxicity outcomes to adaptively determine doses for subsequent patients and identify the optimal biological dose, maximizing the overall therapeutic effect. Specifically, we highlight three categories of phase I-II designs: efficacy-driven, utility-based, and designs incorporating multiple efficacy endpoints. For each design, we review the dose-outcome model, the definition of the optimal biological dose, the dose-finding algorithm, and the software for trial implementation. To illustrate the concepts, we also present two real phase I-II trial examples utilizing the EffTox and ISO designs. Finally, we provide a classification tree to summarize the designs discussed in this article

Development and Application of an Extraction and Quantitative HPLC Method for Sulforaphene in Radish

AbstractSulforaphene, an isothiocyanate generated by the conversion of glucoraphenin in radish (Raphanus sativus L.), plays an important role in plants as a defensive compound and has been shown to have anti-cancer properties. However, a reliable method for the determination of sulforaphene in radish has not yet been established. In the present study, the enzymolysis conditions, extraction solvent and extraction conditions employed to obtain sulforaphene from radish were all optimized using single factor experiments and orthogonal testing. During these trials, sulforaphene was separated and quantified using reverse phase C18 high performance liquid chromatography (HPLC), employing methanol:water (3:7 ν/ν) as the mobile phase at a flow rate of 0.3mL · min−1 together with a detection wavelength of 245nm. Evaluation of this newly established method showed good linearity between the sulforaphene concentration and the characteristic peak area over the range of 5 to 200μg · mL−1 (R2 = 0.9996). This method was thus found to be precise. It was established that sulforaphene was extracted from radish with 95.48% efficiency (RSD = 0.94%) using the optimized conditions. This same technique was successfully applied to the quantification of sulforaphene in the fleshy roots of different radish germplasms as a means of selecting the germplasms with the highest sulforaphene levels