Synthesis, Structure and Electrochemistry of Positive Electrode Materials for Rechargeable Magnesium and Lithium Ion Batteries: Mechanistic Investigations

To meet the requirements for high energy density storage systems, rechargeable batteries based on the “beyond lithium ion” technologies have been widely investigated. The magnesium battery is a promising candidate benefiting from the utilization of a Mg metal negative electrode, which offers high volumetric capacity (3833 mAh mL-1), low redox potential (-2.37 V vs. S.H.E.), non-dendritic growth, low price and safe handling in atmosphere. However, the discovery of potential positive electrode materials beyond the seminal Mo6S8 has been limited, mainly due to the sluggish mobility of a divalent Mg2+ ion in solid frameworks. This thesis presents the research on both finding new positive electrode materials and investigating mechanisms to understand the limitation. Two structures of titanium sulfide are identified as the second family of Mg2+ insertion positive electrodes, offering almost twice the capacity of the benchmark Mo6S8. The facile Mg2+ solid diffusion is mainly supported by the polarizable lattices, while the crystal structure plays a critical rule on the specific diffusion mechanism, which further influences the electrochemistry. While sulfides provide moderate energy density, it can be largely increased by shifting to oxide materials. However, poor electrochemistry has been widely observed for oxide based Mg positive electrode materials. In the present thesis work, a case study with birnessite MnO2 identifies desolvation as a key factor limiting Mg2+ insertion into oxides from nonaqueous electrolytes, while another study with Mg2Mo3O8 demonstrates the strong influence of transition states on setting the magnitude of migration barriers. Those limitations have to be overcome to allow facile Mg2+ insertion into oxides. Alternative setups which would accomplish the advantages of a Mg negative electrode and avoid the sluggish Mg2+ solid diffusion include the Mg-Li hybrid system. Two “high voltage” Prussian blue analogues (average 2.3 V vs. Mg/Mg2+) are investigated as positive electrode materials in the thesis, both showing promising energy density and cycle life. Finally, novel positive electrode materials for Li-ion batteries are examined. The possibility of stabilizing lithium transition-metal silicate in the olivine structure is studied by combined atomistic scale simulation and solid state synthesis, suggesting a potential solution by cation substitution

Unlocking the Promise of Systemic Sting Agonist for Cancer Immunotherapy

Stimulator of interferon genes (STING) pathway is the key innate immune pathway involving in cancer immunity. Emerging new molecules and drug delivery systems have made systemic STING agonist immunotherapy possible and demonstrated efficient tumor eradication in preclinical studies. In this perspective, we will discuss the potential mechanisms of STING agonism as a multifaceted anti-cancer therapy and the pharmacological challenges associated with systemic delivery of STING agonists on the level of organs, tissues, cells, and intracellular compartments. We will present and discuss drug delivery strategies to address these challenges. New advances in the field can unlock the promise of systemic STING agonist as effective and safe cancer immunotherapy

Generating Moving Average Trading Rules on the Oil Futures Market with Genetic Algorithms

The crude oil futures market plays a critical role in energy finance. To gain greater investment return, scholars and traders use technical indicators when selecting trading strategies in oil futures market. In this paper, the authors used moving average prices of oil futures with genetic algorithms to generate profitable trading rules. We defined individuals with different combinations of period lengths and calculation methods as moving average trading rules and used genetic algorithms to search for the suitable lengths of moving average periods and the appropriate calculation methods. The authors used daily crude oil prices of NYMEX futures from 1983 to 2013 to evaluate and select moving average rules. We compared the generated trading rules with the buy-and-hold (BH) strategy to determine whether generated moving average trading rules can obtain excess returns in the crude oil futures market. Through 420 experiments, we determine that the generated trading rules help traders make profits when there are obvious price fluctuations. Generated trading rules can realize excess returns when price falls and experiences significant fluctuations, while BH strategy is better when price increases or is smooth with few fluctuations. The results can help traders choose better strategies in different circumstances

Resilience to Plasma and Cerebrospinal Fluid Amyloid-β in Cognitively Normal Individuals: Findings From Two Cohort Studies.

Objective: To define resilience metrics for cognitive decline based on plasma and cerebrospinal fluid (CSF) amyloid-β (Aβ) and examine the demographic, genetic, and neuroimaging factors associated with interindividual differences among metrics of resilience and to demonstrate the ability of such metrics to predict the diagnostic conversion to mild cognitive impairment (MCI). Methods: In this study, cognitively normal (CN) participants with Aβ-positive were included from the Sino Longitudinal Study on Cognitive Decline (SILCODE, n = 100) and Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 144). Using a latent variable model of data, metrics of resilience [brain resilience (BR), cognitive resilience (CR), and global resilience (GR)] were defined based on the plasma Aβ and CSF Aβ. Linear regression analyses were applied to investigate the association between characteristics of individuals (age, sex, educational level, genetic, and neuroimaging factors) and their resilience. The plausibility of these metrics was tested using linear mixed-effects models and Cox regression models in longitudinal analyses. We also compared the effectiveness of these metrics with conventional metrics in predicting the clinical progression. Results: Although individuals in the ADNI cohort were older (74.68 [5.65] vs. 65.38 [4.66], p < 0.001) and had higher educational levels (16.3 [2.6] vs. 12.6 [2.8], p < 0.001) than those in the SILCODE cohort, similar loadings between resilience and its indicators were found within both models. BR and GR were mainly associated with age, women, and brain volume in both cohorts. Prediction models showed that higher CR and GR were related to better cognitive performance, and specifically, all types of resilience to CSF Aβ could predict longitudinal cognitive decline. Conclusion: Different phenotypes of resilience depending on cognition and brain volumes were associated with different factors. Such comprehensive resilience provided insight into the mechanisms of susceptibility for Alzheimer's disease (AD) at the individual level, and interindividual differences in resilience had the potential to predict the disease progression in CN people

Improving STING Agonist Delivery for Cancer Immunotherapy Using Biodegradable Mesoporous Silica Nanoparticles

Stimulator of interferon genes (STING) activation by intratumoral STING agonist treatment has been recently shown to eradicate tumors in preclinical models of cancer immunotherapy, generating intense research interest and leading to multiple clinical trials. However, there are many challenges associated with STING agonist‐based cancer immunotherapy, including low cellular uptake of STING agonists. Here, biodegradable mesoporous silica nanoparticles (bMSN) with an average size of 80 nm are developed for efficient cellular delivery of STING agonists. STING agonists delivered via bMSN potently activate innate and adaptive immune cells, leading to strong antitumor efficacy and prolonged animal survival in murine models of melanoma. Delivery of immunotherapeutic agents via biodegradable bMSN is a promising approach for improving cancer immunotherapy.Biodegradable mesoporous silica nanoparticles enhance cellular delivery of stimulator of interferon genes (STING) agonists and achieve greater antitumor therapeutic efficacy than free STING agonists in murine models of melanoma. Biodegradable mesoporous silica nanoparticles are a promising platform for cancer immunotherapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163388/3/adtp202000130_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163388/2/adtp202000130.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163388/1/adtp202000130-sup-0001-SuppMat.pd

Chishao (Paeoniae Radix Rubra) alleviates intra-hepatic cholestasis by modulating NTCP in rats

Background: Cholestasis is a common pathological manifestation dominated by accumulation of potentially toxic biliary compounds. Na+-taurocholate cotransporting polypeptide (NTCP) plays a critical role in protection from cholestasis and can be targeted therapeutically. Chishao (Paeoniae Radix Rubra) is a clinically efficacious agent for treating cholestasis, but the underlying mechanism has not been fully clarified.Objective: To evaluate the effects of Chishao on the expression of NTCP in rats with alpha-naphthylisothiocyanate (ANIT)-induced cholestasis.Methods: Chishao extracts were obtained by water decoction. Cholestasis model induced by ANIT in rats were established. Thirty rats were divided into five groups: control group (C), ANIT model group (M), 10 g/kg Chishao group (LD), 20 g/kg Chishao group (MD) and 40 g/kg Chishao group (HD). The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB), alkaline phosphatase (ALP) and total bile acid (TBA) were detected. The mRNA and protein expression of NTCP, multidrug resistance associated protein 2 (MRP2) and bile salt export pump (BSEP) were detected by reverse transcription qPCR and Western blotting respectively. To assess the effects of Chishao on NTCP, MRP2 and BSEP localized at the membrane of hepatocytes, an in vitro experiment involving primary hepatocytes was conducted via the utilization of laser scanning confocal microscopy.Results: The extracts of Chishao significantly improved serum ALT, AST, ALP, TB, DB and TBA (p &lt; 0.05), especially ALP in the HD group (p &lt; 0.01). The histological pathological findings were also reversed in LD, MD and HD groups. The mRNA level of MRP2 was significantly downregulated after treatment with ANIT, whereas it was reversed in MD and HD groups (p &lt; 0.05). The mRNA expression of NTCP was significantly downregulated after ANIT treatment, but dramatically upregulated in the HD group. The expressions of BSEP and MRP2 were similar, but that of NTCP decreased after ANIT treatment, which was reversed significantly by Chishao extracts in a dose-dependent manner. The expression of NTCP in hepatocytes from rats increased dose-dependently after Chishao treatment in vitro.Conclusion: Chishao extracts can improve the serum and histological performances of intra-hepatic cholestasis caused by ANIT, probably by working on transport proteins in liver cell membranes