Photocatalytic Activation of Saturated C–H Bond Over the CdS Mixed-Phase Under Visible Light Irradiation

Selective activation of saturated C–H bond in hydrocarbons to produce high-value-added chemicals is of great significance for chemical synthesis and transformation. Herein, we present a facile procedure to achieve Ni-doped CdS nanoparticles with mixed (cubic and hexagonal) phases, as well as its application to the photocatalytic activation of saturated primary C–H bond of toluene and its derivatives. The photocatalytic oxidation rate of toluene into benzaldehyde of formation reached up to 216.7 μmolh−1g−1 under visible light irradiation. The excellent photocatalytic performance of Ni(II)-doped CdS [Ni(II)/CdS] can be attributed to its unique structural assembly with cubic and hexagonal phases and also the addition of Ni ions, together taking effect in promoting the separation of photogenerated charge carriers. The possible reaction mechanism for the photocatalytic selective oxidation is illustrated in this work. The band width of the as-prepared mixed phase CdS is reduced, which can effectively expand the response range and improve photocatalytic performance

Potential of DNMT and its Epigenetic Regulation for Lung Cancer Therapy

Lung cancer, the leading cause of mortality in both men and women in the United States, is largely diagnosed at its advanced stages that there are no effective therapeutic alternatives. Although tobacco smoking is the well established cause of lung cancer, the underlying mechanism for lung tumorigenesis remains poorly understood. An important event in tumor development appears to be the epigenetic alterations, especially the change of DNA methylation patterns, which induce the most tumor suppressor gene silence. In one scenario, DNA methyltransferase (DNMT) that is responsible for DNA methylation accounts for the major epigenetic maintenance and alternation. In another scenario, DNMT itself is regulated by the environment carcinogens (smoke), epigenetic and genetic information. DNMT not only plays a pivotal role in lung tumorigenesis, but also is a promising molecular bio-marker for early lung cancer diagnosis and therapy. Therefore the elucidation of the DNMT and its related epigenetic regulation in lung cancer is of great importance, which may expedite the overcome of lung cancer

Nitrogen-doped carbon coated ZeO2 as a support to Pt nanoparticles in the oxygen reduction reaction

A new nitrogen-doped carbon (CNx) support for Pt electrocatalysts was prepared by carbonizing polypyrrole on the surface of ZrO2 (ZrO2@CNx) at high temperature. Well-dispersed Pt nanoparticles were easily formed on the ZrO2@CNx. The electrocatalyst was characterized by FT-IR, XRD, TEM, XPS. The electrochemical performances indicate that the presence of ZrO2 modified the electro-structure of Pt on the catalyst surface and that ZrO2@CNx had superior oxygen reduction activity compared to a nitrogen-doped carbon coated carbon (C@CNx).Web of Scienc

Montmorillonite modified by CNx supported Pt for methanol oxidation

A composite support based on nature clay, i.e. montmorillonite (MMT), shows great promise as support materials for Pt electrocatalyst for the methanol oxidation reaction in fuel cell anodes. The reported composite support (CNx-MMT) was prepared via carbonizing MMT which was covered by N-contented polymer. X-ray diffraction and transmission electron microscopy results showed that Pt nanoparticles can be well-dispersed on the composite support with highly dispersed tiny crystal Pt nanoparticles. Cyclic voltammetry measurements showed that the Pt/CNx-MMT has the enhanced electrocatalytic activity in methanol oxidation reaction. The developed Pt catalyst supported on new composite support is catalytically more active for methanol electrooxidation than Pt supported on the conventional carbon support and shows good stability, offering promising potential for application of MMT as support for fuel cell electrocatalysis.Web of Scienc

The Transcription Factor T-Bet Is Required for Optimal Type I Follicular Helper T Cell Maintenance During Acute Viral Infection

Follicular helper T cells (TFH cells), known as the primary “helpers” of the germinal center (GC) reaction, promote the humoral immune response to defend against various pathogens. Under conditions of infection by different types of pathogens, many shared transcription factors (TFs), such as Bcl-6, TCF-1, and Maf, are selectively enriched in pathogen-specific TFH cells, orchestrating TFH cell differentiation and function. In addition, TFH cells also coexpress environmentally associated TFs as their conventional T cell counterparts (such as T-bet, GATA-3, or ROR-γt, which are expressed in Th1, Th2, or Th17 cells, respectively). These features likely indicate both the lineage-specificity and environmental adaption of the TFH cell responses. However, the extent to which the TFH cell response relies on these environmentally specific TFs is not completely understood. Here, we found that T-bet was specifically expressed in Type I TFH cells but not Type II TFH cells. While dispensable for the early fate commitment of TFH cells, T-bet was essential for the maintenance of differentiated TFH cells, promoting their proliferation, and inhibiting their apoptosis during acute viral infection. Microarray analysis showed both similarities and differences in transcriptome dependency on T-bet in TFH and TH1 cells, suggesting the distinctive role of T-bet in TFH cells. Collectively, our findings reveal an important and specific supporting role for T-bet in type I TFH cell response, which can help us gain a deeper understanding of TFH cell subsets

CNx-modified Fe3O4 as Pt nanoparticle support for the oxygen reduction reaction

A novel electrocatalyst support material, nitrogendoped carbon (CNx)-modified Fe3O4 (Fe3O4-CNx), was synthesized through carbonizing a polypyrrole-Fe3O4 hybridized precursor. Subsequently, Fe3O4-CNx-supported Pt (Pt/Fe3O4-CNx) nanocomposites were prepared by reducing Pt precursor in ethylene glycol solution and evaluated for the oxygen reduction reaction (ORR). The Pt/Fe3O4-CNx catalysts were characterized by X-ray diffraction, Raman spectra, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. The electrocatalytic activity and stability of the as-prepared electrocatalysts toward ORR were studied by cyclic voltammetry and steady-state polarization measurements. The results showed that Pt/ Fe3O4-CNx catalysts exhibited superior catalytic performance for ORR to the conventional Pt/C and Pt/C-CNx catalysts.Web of Scienc

The Transcription Factor TCF1 Preserves the Effector Function of Exhausted CD8 T Cells During Chronic Viral Infection

The long-term persistence of viral antigens drives virus-specific CD8 T cell exhaustion during chronic viral infection. Yet exhausted, CD8 T cells are still endowed with certain levels of effector function, by which they can keep viral replication in check in chronic infection. However, the regulatory factors involved in regulating the effector function of exhausted CD8 T cell are largely unknown. Using mouse model of chronic LCMV infection, we found that the deletion of transcription factor TCF-1 in LCMV-specific exhausted CD8 T cells led to the profound reduction in cytokine production and degranulation. Conversely, ectopic expression of TCF-1 or using agonist to activate TCF-1 activities promotes the effector function of exhausted CD8 T cells. Mechanistically, TCF-1 fuels the functionalities of exhausted CD8 T cells by promoting the expression of an array of key effector function-associated transcription regulators, including Foxo1, Zeb2, Id3, and Eomes. These results collectively indicate that targeting TCF-1 mediated transcriptional pathway may represent a promising immunotherapy strategy against chronic viral infections by reinvigorating the effector function of exhausted virus-specific CD8 T cells

Mouse γ-Synuclein Promoter-Mediated Gene Expression and Editing in Mammalian Retinal Ganglion Cells

Optic neuropathies are a group of optic nerve (ON) diseases caused by various insults including glaucoma, inflammation, ischemia, trauma, and genetic deficits, which are characterized by retinal ganglion cell (RGC) death and ON degeneration. An increasing number of genes involved in RGC intrinsic signaling have been found to be promising neural repair targets that can potentially be modulated directly by gene therapy, if we can achieve RGC specific gene targeting. To address this challenge, we first used adeno-associated virus (AAV)-mediated gene transfer to perform a low-throughput in vivo screening in both male and female mouse eyes and identified the mouse γ-synuclein (mSncg) promoter, which specifically and potently sustained transgene expression in mouse RGCs and also works in human RGCs. We further demonstrated that gene therapy that combines AAV-mSncg promoter with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing can knock down pro-degenerative genes in RGCs and provide effective neuroprotection in optic neuropathies.SIGNIFICANCE STATEMENT Here, we present an RGC-specific promoter, mouse γ-synuclein (mSncg) promoter, and perform extensive characterization and proof-of-concept studies of mSncg promoter-mediated gene expression and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing in RGCs in vivo To our knowledge, this is the first report demonstrating in vivo neuroprotection of injured RGCs and optic nerve (ON) by AAV-mediated CRISPR/Cas9 inhibition of genes that are critical for neurodegeneration. It represents a powerful tool to achieve RGC-specific gene modulation, and also opens up a promising gene therapy strategy for optic neuropathies, the most common form of eye diseases that cause irreversible blindness

Minimal Essential Human Factor VIII Alterations Enhance Secretion and Gene Therapy Efficiency

One important limitation for achieving therapeutic expression of human factor VIII (FVIII) in hemophilia A gene therapy is inefficient secretion of the FVIII protein. Substitution of five amino acids in the A1 domain of human FVIII with the corresponding porcine FVIII residues generated a secretion-enhanced human FVIII variant termed B-domain-deleted (BDD)-FVIII-X5 that resulted in 8-fold higher FVIII activity levels in the supernatant of an in vitro cell-based assay system than seen with unmodified human BDD-FVIII. Analysis of purified recombinant BDD-FVIII-X5 and BDD-FVIII revealed similar specific activities for both proteins, indicating that the effect of the X5 alteration is confined to increased FVIII secretion. Intravenous delivery in FVIII-deficient mice of liver-targeted adeno-associated virus (AAV) vectors designed to express BDD-FVIII-X5 or BDD-FVIII achieved substantially higher plasma FVIII activity levels for BDD-FVIII-X5, even when highly efficient codon-optimized F8 nucleotide sequences were employed. A comprehensive immunogenicity assessment using in vitro stimulation assays and various in vivo preclinical models of hemophilia A demonstrated that the BDD-FVIII-X5 variant does not exhibit an increased immunogenicity risk compared to BDD-FVIII. In conclusion, BDD-FVIII-X5 is an effective FVIII variant molecule that can be further developed for use in gene- and protein-based therapeutics for patients with hemophilia A

FMCW radar implemented with GNU Radio Companion

Continuous-wave frequency-modulated radar, or FMCW radar, is simple in design, small in size and weight and uses low transmitting power. The range resolution depends on the bandwidth. FMCWradar is used in applications ranging from guided weapons systems to vehicle collision avoidance systems. Measuring the distance to the target is the essential feature of FMCW radar. Firstly, this thesis introduces the basic structure of the FMCW radar and the principle formeasuring distance. Secondly, by using software-dened radio (SDR),FMCW radar can be implemented and congured with a reduced costand complexity. In this report, the radar is implemented by means ofthe software GNU Radio Companion with a test signal. HackRF may be used in future work with an osmocom source instead of the testsignal