REDOX FLOW LITHIUM BATTERY: PROOF OF CONCEPT AND STUDIES ON THE CATHODIC COMPARTMENT

Ph.DDOCTOR OF PHILOSOPH

Molecular Basis of the Differentiation and Function of Virus Specific Follicular Helper CD4+ T Cells

During viral infection, virus-specific follicular helper T cells provide important help to cognate B cells for their survival, consecutive proliferation and mutation and eventual differentiation into memory B cells and antibody-secreting plasma cells. Similar to Tfh cells generated in other conditions, the differentiation of virus-specific Tfh cells can also be characterized as a process involved multiple factors and stages, however, which also exhibits distinct features. Here, we mainly focus on the current understanding of Tfh fate commitment, functional maturation, lineage maintenance and memory transition and formation in the context of viral infection

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

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

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

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

High-Energy Density Redox Flow Lithium Battery with Unprecedented Voltage Efficiency

A redox flow lithium battery (RFLB) has decoupled energy storage and power generation units like a conventional redox flow battery, while it stores energy in solid materials by virtue of the unique redox targeting concept. Hence, it presents superior energy density and represents a promising approach for large-scale energy storage. In a RFLB, the potential difference between the redox shuttle molecules used in the same electrolyte normally brings about an intrinsic voltage hysteresis, resulting in a compromised voltage efficiency of the battery. Here we report a novel redox shuttle molecule pair to minimize the voltage hysteresis: anatase TiO₂ is reduced by bis­(pentamethylcyclopentadienyl)­chromium (CrCp*₂), while Li_<i>x</i>TiO₂ is oxidized by cobaltocene (CoCp₂). The potential difference between CoCp₂ and CrCp*₂ is only 0.15 V. A redox flow lithium battery is successfully demonstrated with an unprecedented voltage efficiency of 84%. The RFLB shows good cycling stability, and >90% Coulombic efficiency was demonstrated in the first 50 cycles

Kinetics of Li_<i>x</i>FePO₄ Lithiation/Delithiation by Ferrocene-Based Redox Mediators: An Electrochemical Approach

An electrochemical approach for studying the kinetics of reactions between redox mediators and Li-ion battery electrode materials has been developed. The approach is based on a simple diffusion-reaction model, similar to that used to describe the classical catalytic electrochemical–chemical (EC′) reaction mechanism. Using this approach it is possible to determine the diffusion length of redox mediators in a porous film made from a Li-ion battery electrode material. The rate constant for reaction between redox species and the porous electrode may then be calculated. The approach is applied to determine rate constants for the disappearance of ferrocene and dibromoferrocenium due to reaction with excess pristine and carbon-coated Li_<i>x</i>FePO₄ (0 ≤ <i>x</i> ≤ 1) nanoparticulate films (porosity ∼0.63, BET surface area 20–30 m² g^–1) and excess Li⁺ (0.1 M), which are of relevance to the operation of the recently introduced redox-flow Li-ion battery. Pseudo-first-order volumetric rate constants in the range 1–6 s^–1 were obtained, corresponding to apparent heterogeneous rate constants in the range 2.2 × 10^–6 – 4.4 × 10^–6 cm s^–1, which we show are fast enough not to limit the charge/discharge rate of redox flow Li-ion batteries constructed from these materials