DEVELOPING HIGH-THROUGHPUT APPROACHES FOR ENZYME SCREENING AND PROTEOMIC PROFILING

Ph.DDOCTOR OF PHILOSOPH

Inhibition of HSP90 distinctively modulates the global phosphoproteome of Leishmania mexicana developmental stages

Heat shock protein 90 (HSP90) is an evolutionarily conserved chaperone protein that plays a central role in the folding and maturation of a large array of client proteins. In the unicellular parasite Leishmania, the etiological agent of the neglected tropical disease leishmaniasis, treatment with HSP90 inhibitors leads to differentiation from promastigote to amastigote stage, resembling the effects of established environmental triggers, low pH and heat shock. This indicates a crucial role for HSP90 in the life cycle control of Leishmania. However, the underlying molecular mechanisms remain unknown. Using a combination of treatment with the classical HSP90 inhibitor tanespimycin, phosphoproteome enrichment, and tandem mass tag (TMT) labeling-based quantitative proteomic mass spectrometry (MS), we systematically characterized the perturbing effect of HSP90 inhibition on the global phosphoproteome of Leishmania mexicana across its life cycle stages and showed that the HSP90 inhibition causes substantially distinct molecular effects in promastigote and amastigote forms.While phosphorylation of HSP90 and its co-chaperone HSP70 was decreased in amastigote, the opposite effect was observed in promastigotes. Our results showed that kinase activity and microtubule motor activity are highly represented in the negatively affected phosphoproteins of the promastigotes, whereas ribosomal proteins, protein folding, and proton channel activity are preferentially enriched in the perturbed amastigote phosphoproteome. Additionally, cross-comparison of our results with HSP90 inhibition-affected RNA-binding proteins showed that RNA helicase domains were distinctively enriched among the upregulated amastigote phosphoproteins. In addition to providing robust identification and quantification of 1,833 phosphorylated proteins across three life cycle stages of L. mexicana, this study reveals the dramatically different ways the HSP90 inhibition stress modulates the phosphoproteome of the pathogenic amastigote and provides in-depth insight into the scope of selective molecular targeting in the therapeutically relevant amastigote stage

A Review of Resveratrol as a Potent Chemoprotective and Synergistic Agent in Cancer Chemotherapy

Background: Cancer has become a major disease endangering human health around the world. Conventional chemotherapy suffers from many side effects including pain, cardiotoxicity, hepatotoxicity, and renal toxicity. This review aims to describe a natural product of resveratrol as a chemoprotective and synergistic agent in the modulation of cancer chemotherapy.Methods: The publications were identified by comprehensive searching of SciFinder, PubMed, Web of Science, and our own reference library. Search terms included combinations of “resveratrol,” “cancer,” “natural products,” “chemotherapy,” and “side effects.” Selection of material focused on resveratrol reducing the side effects on cancer chemotherapy.Results: Thirty one references were referred in this review to outline resveratrol as a potent chemoprotective and synergistic agent in cancer chemotherapy, including 22 papers for describing the chemoprotective effects, and 9 papers for illustrating the synergistic effects.Conclusion: This study provides a systematic summary of resveratrol serving as a potent chemoprotective and synergistic agent to reduce the associated-side effects and enhance the therapeutic outcomes in cancer chemotherapy. Further studies in terms of resveratrol on a large amount of preclinical tests and clinical trials are highly demanded

Obtaining and using A-correlation information on stocks via the internet

This thesis introduces two stock analysis software packages. The software packages are designed to gather stock data over the Internet, and process the gathered data to determine an approximate correlation (A-correlation) between a reference stock and a set of comparison stocks.In this thesis, the A-correlation is obtained from historical stock data using data mining techniques. The data mining techniques include a data retrieval and analysis algorithm. First, a large pool of stock data is retrieved from the CNBC web site by employing an Internet data retrieval algorithm. Then an analysis algorithm is applied to determine the A-correlation between a reference stock and each of a set of the comparison stocks. The analysis algorithm is based on the accumulation of individual stock movements (up/down) over a period of time.We have designed and implemented the two programs using Microsoft Excel/VBA. The two programs share common functionalities such as providing the A-correlation as a function of time, ranking the A-correlation results in a predefined order, and allowing the user to spot possible A-correlation trends. The difference between the two programs is that the first program analyses A-correlation with no time delay and the second program deals with the time delayed A-correlation. Each program can be useful in revealing different aspects of the relationships between stocks. These two programs can be useful tools for stock market analysis

Unraveling the Multifaceted Nexus of Artificial Intelligence Sports and User Willingness: A Focus on Technology Readiness, Perceived Usefulness, and Green Consciousness

The adoption of artificial intelligence (AI) in the sports domain, known as AI Sports, has gained considerable attention, while the increasing importance of environmental sustainability further necessitates exploring green-conscious behaviors. This study aims to investigate the impacts of technology readiness, perceived usefulness, and green consciousness on users’ willingness to adopt AI Sports. Utilizing a cross-sectional survey and structural equation modeling, data from 670 valid questionnaires were analyzed. The results revealed that technology readiness directly influences users’ perceived usefulness of AI Sports, while green awareness significantly affects perceived usefulness, highlighting the relative scarcity of research on green consciousness in this context. Moreover, perceived usefulness plays a crucial role in predicting users’ willingness to use AI Sports, contributing to its sustainable development and widespread adoption. This study fills a research gap by exploring the importance of green consciousness in the field of artificial intelligence sports, and provides important insights for the development and promotion of sustainable artificial intelligence sports

Analysis and Nursing Health Education of Current Status of Maintenance Hemodialysis Patients with Hyperphosphatemia

Concerned about the current situation of hemodialysis patients' awareness of the problems related to dialysis complicated with hyperphosphatemia, further analyze the existing problems and causes, give targeted and individualized health education, improve the compliance of diet, medication and self-management, strengthen nurse-patient communication, establish a good nurse-patient relationship, reduce and control the incidence of hyperphosphatemia, improve patients' quality of life, and improve prognosis

An Artificial Chameleon Skin for Dynamic Thermoregulation

Abstract Solar radiation is the major energy source for most living creatures, and some creatures change their skin colors responding to energy demands. Inspired by the chameleons that live in the desert of Namibia, which can regulate body temperature by changing skin colors between black and white, a patterned hydrogel film with self‐thermoregulation ability is reported in this work. The film consists of two parts: a light‐responsive black part and a stretchable white part. The black part is made of thermoresponsive poly(N‐isopropylacrylamide) hydrogel with polydopamine (PDA) nanoparticles, and the white part is made of stretchable polyacrylamide hydrogel with polystyrene (PS) nanoparticles. At low temperature and low light irradiation, the black part dominates the film, and the embedded melanin‐like PDA nanoparticles adsorb light and convert it to heat, thus reaching an active body temperature. At high temperature and strong light irradiation, the black part shrinks, which in turn stretches the white part to dominate the film, and more light is reflected by guanine crystals‐like PS nanoparticles, thus protecting body temperature from rising. The combination of the thermoresponsive black hydrogel and stretchable white hydrogel provides an evolutionary novelty that can control the solar lights for dynamic thermoregulation

Determination and Pharmacokinetic Study of Three Diterpenes in Rat Plasma by UHPLC-ESI-MS/MS after Oral Administration of Rosmarinus officinalis L. Extract

Rosmarinus officinalis L. is commonly used as a spice and flavoring agent. Diterpenes are the main active compounds of R. officinalis. An Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-ESI-MS/MS) method was developed for the determination of carnosol, rosmanol, and carnosic acid isolated from R. officinalis in rat plasma, and applied to a pharmacokinetic study after oral administration of R. officinalis extract. Sample preparation involved a liquid-liquid extraction of the analytes with ethyl acetate. Butylparaben was employed as an internal standard (I.S.). Chromatographic separation was carried out on a C18 column (ACQUITY UPLC® HSS T3, 1.8 μm, 2.1 mm × 100 mm) with a gradient system consisting of the mobile phase solution A (0.1% formic acid in water) and solution B (acetonitrile) at the flow rate of 0.3 mL/min. The quantification was obtained using multiple reaction monitoring (MRM) mode with electrospray ionization (ESI). The UHPLC-MS/MS assay was validated for linearity, accuracy, precision, extraction recovery, matrix effect and stability. This study described a simple, sensitive and validated UHPLC-MS/MS method for the simultaneous determination of three diterpene compounds in rat plasma after oral administration of R. officinalis extract, and investigated on their pharmacokinetic studies as well