Browsing by Author "Wang, Hua"
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Item Aging exaggerates acute-on-chronic alcohol-induced liver injury in mice and humans by inhibiting neutrophilic sirtuin 1-C/EBPα-miRNA-223 axis(Wolters Kluwer, 2022) Ren, Ruixue; He, Yong; Ding, Dong; Cui, Aoyuan; Bao, Huarui; Ma, Jing; Hou, Xin; Li, Yu; Feng, Dechun; Li, Xiaoling; Liangpunsakul, Suthat; Gao, Bin; Wang, Hua; Medicine, School of MedicineBackground and aims: Aging exacerbates liver neutrophil infiltration and alcohol-associated liver disease (ALD) in mice and humans, but the underlying mechanisms remain obscure. This study aimed to examine the effect of aging and alcohol consumption on neutrophilic Sirtuin 1 (SIRT1) and microRNA-223 (miR-223), and their contribution to ALD pathogeneses. Approach and results: Young and aged myeloid-specific Sirt1 knockout mice were subjected to chronic-plus-binge ethanol feeding. Blood samples from healthy controls and patients with chronic alcohol drinking who presented with acute intoxication were analyzed. Neutrophilic Sirt1 and miR-223 expression were down-regulated in aged mice compared with young mice. Deletion of the Sirt1 gene in myeloid cells including neutrophils exacerbated chronic-plus-binge ethanol-induced liver injury and inflammation and down-regulated neutrophilic miR-223 expression. Immunoprecipitation experiments revealed that SIRT1 promoted C/EBPα deacetylation by directly interacting with C/EBPα, a key transcription factor that controls miR-223 biogenesis, and subsequently elevated miR-223 expression in neutrophils. Importantly, down-regulation of SIRT1 and miR-223 expression was also observed in circulating neutrophils from middle-aged and elderly subjects compared with those from young individuals. Chronic alcohol users with acute intoxication had a reduction in neutrophilic SIRT1 expression in young and middle-aged patients, with a greater reduction in the latter group. The neutrophilic SIRT1 expression correlated with neutrophilic miR-223 and serum alanine transaminase levels in those patients. Conclusions: Aging increases the susceptibility of alcohol-induced liver injury in mice and humans through the down-regulation of the neutrophilic SIRT1-C/EBPα-miR-223 axis, which could be a therapeutic target for the prevention and/or treatment of ALD.Item Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance(Ingenta, 2017-07-07) Gao, Bin; Xu, Ming-Jiang; Bertola, Adeline; Wang, Hua; Zhou, Zhou; Liangpunsakul, Suthat; Medicine, School of MedicineAlcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide, comprises a range of disorders including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal models for the study of ALD pathogenesis have been developed. Recently, a chronic-plus-binge ethanol feeding model was reported. This model induces significant steatosis, hepatic neutrophil infiltration, and liver injury. A clinically relevant model of high-fat diet feeding plus binge ethanol was also developed, which highlights the risk of excessive binge drinking in obese/overweight individuals. All of these models recapitulate some features of the different stages of ALD and have been widely used by many investigators to study the pathogenesis of ALD and to test for therapeutic drugs/components. However, these models are somewhat variable, depending on mouse genetic background, ethanol dose, and animal facility environment. This review focuses on these models and discusses these variations and some methods to improve the feeding protocol. The pathogenesis, clinical relevance, and translational studies of these models are also discussed.Item Diabetes mellitus promotes the nasal colonization of high virulent Staphylococcus aureus through the regulation of SaeRS two-component system(Taylor & Francis, 2023) Wang, Qichen; Nurxat, Nadira; Zhang, Lei; Liu, Yao; Wang, Yanan; Zhang, Lei; Zhao, Na; Dai, Yingxin; Jian, Ying; He, Lei; Wang, Hua; Bae, Taeok; Li, Min; Liu, Qian; Microbiology and Immunology, School of MedicineDiabetic foot infections are a common complication of diabetes. Staphylococcus aureus is frequently isolated from diabetic foot infections and commonly colonizes human nares. According to the study, the nasal microbiome analysis revealed that diabetic patients had a significantly altered nasal microbial composition and diversity. Typically, the fasting blood glucose (FBG) level had an impact on the abundance and sequence type (ST) of S. aureus in diabetic patients. We observed that highly virulent S. aureus ST7 strains were more frequently colonized in diabetic patients, especially those with poorly controlled FBG, while ST59 was dominant in healthy individuals. S. aureus ST7 strains were more resistant to human antimicrobial peptides and formed stronger biofilms than ST59 strains. Critically, S. aureus ST7 strains displayed higher virulence compared to ST59 strains in vivo. The dominance of S. aureus ST7 strains in hyperglycemic environment is due to the higher activity of the SaeRS two-component system (TCS). S. aureus ST7 strains outcompeted ST59 both in vitro, and in nasal colonization model in diabetic mice, which was abolished by the deletion of the SaeRS TCS. Our data indicated that highly virulent S. aureus strains preferentially colonize diabetic patients with poorly controlled FBG through SaeRS TCS. Detection of S. aureus colonization and elimination of colonizing S. aureus are critical in the care of diabetic patients with high FBG.Item Effect of Cationic (Na+) and Anionic (F-) Co-Doping on the Structural and Electrochemical Properties of LiNi1/3Mn1/3Co1/3O2 Cathode Material for Lithium-Ion Batteries(MDPI, 2022-06-17) Wang, Hua; Hashem, Ahmed M.; Abdel-Ghany, Ashraf E.; Abbas, Somia M.; El-Tawil, Rasha S.; Li, Tianyi; Li, Xintong; El-Mounayri, Hazim; Tovar, Andres; Zhu, Likun; Mauger, Alain; Julien, Christian M.; Mechanical and Energy Engineering, School of Engineering and TechnologyElemental doping for substituting lithium or oxygen sites has become a simple and effective technique to improve the electrochemical performance of layered cathode materials. Compared with single-element doping, this work presents an unprecedented contribution to the study of the effect of Na+/F- co-doping on the structure and electrochemical performance of LiNi1/3Mn1/3Co1/3O2. The co-doped Li1-zNazNi1/3Mn1/3Co1/3O2-zFz (z = 0.025) and pristine LiNi1/3Co1/3Mn1/3O2 materials were synthesized via the sol-gel method using EDTA as a chelating agent. Structural analyses, carried out by X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy, revealed that the Na+ and F- dopants were successfully incorporated into the Li and O sites, respectively. The co-doping resulted in larger Li-slab spacing, a lower degree of cation mixing, and the stabilization of the surface structure, which substantially enhanced the cycling stability and rate capability of the cathode material. The Na/F co-doped LiNi1/3Mn1/3Co1/3O2 electrode delivered an initial specific capacity of 142 mAh g-1 at a 1C rate (178 mAh g-1 at 0.1C), and it maintained 50% of its initial capacity after 1000 charge-discharge cycles at a 1C rate.Item Molybdopterin biosynthesis pathway contributes to the regulation of SaeRS two-component system by ClpP in Staphylococcus aureus(Taylor & Francis, 2022) Zhao, Na; Wang, Yanan; Liu, Junlan; Yang, Ziyu; Jian, Ying; Wang, Hua; Ahmed, Mahmoud; Li, Min; Bae, Taeok; Li, Qian; Biology, School of ScienceIn Staphylococcus aureus, the SaeRS two-component system is essential for the bacterium's hemolytic activity and virulence. The Newman strain of S. aureus contains a variant of SaeS sensor kinase, SaeS L18P. Previously, we showed that, in the strain Newman, SaeS L18P is degraded by the membrane-bound protease FtsH. Intriguingly, the knockout mutation of clpP, encoding the cytoplasmic protease ClpP, greatly reduces the expression of SaeS L18P. Here, we report that, in the strain Newman, the positive regulatory role of ClpP on the SaeS L18P expression is due to its destabilizing effect on FtsH and degradation of MoeA, a molybdopterin biosynthesis protein. Although the transcription of ftsH was not affected by ClpP, the expression level of FtsH was increased in the clpP mutant. The destabilizing effect appears to be indirect because ClpXP did not directly degrade FtsH in an in vitro assay. Through transposon mutagenesis, we found out that the moeA gene, encoding the molybdopterin biosynthesis protein A, suppresses the hemolytic activity of S. aureus along with the transcription and expression of SaeS L18P. In a proteolysis assay, ClpXP directly degraded MoeA, demonstrating that MoeA is a substrate of the protease. In a murine bloodstream infection model, the moeA mutant displayed reduced virulence and lower survival compared with the WT strain. Based on these results, we concluded that ClpP positively controls the expression of SaeS L18P in an FtsH and MoeA-dependent manner, and the physiological role of MoeA outweighs its suppressive effect on the SaeRS TCS during infection.Item Multi-level requirement model and its implementation for medical device(2018-08) Wang, Hua; Chen, Jie; Li, Shuning; Dalir, HamidRequirements determine the expectations for a new or modified product. Requirements engineering involves defining, documentation and maintenance of requirements. The rapid improving of technologies and changing of market needs require a shorter time to market and more diversified products. As an important and complex task in product development, it is a huge work to develop new requirements for each new product from scratch. The reusability of requirements data becomes more and more important. However, with the current “copy and paste” approach, engineers have to go through the entire set of requirements (sometimes even more than one set of requirements) to identify the ones which need to be reused or updated. It takes a lot of time and highly relies on the engineers’ experiences. Software tools can only make it easier to capture and locate the requirements, but won’t be able to solve the problem of effective reuse of the existing requirement data. The overall goal of this research is to develop a new model to improve the management of requirements and make the reuse and reconfiguration of existing requirements and requirement models more efficient. Considering the requirements data as an important part of the knowledge body of companies, we followed the knowledge categorization method to classify requirements into groups, which were called levels in the study, based on their changing frequency. There are four levels, the regulatory level, the product line level, the product level and the project level. The regulatory level is the most stable level. Requirements in this level were derived from government and industry regulations. The product line level contains the common requirements for a group of products, the product line. The third level, product level, refers to the specific requirements of the product. And the fourth and most dynamic level, the project level, is about the specific configurations of a product for a project. We chose auto-injector as the application to implement the model, since it is a relatively simple product, but its requirements cover many different categories. There are three major steps in our research approach for the project. The first is to develop requirements and classify them for our model. The development of requirements adopts the goal-oriented model to analyze and SysML, a system modeling language, to build requirements model. And the second step is to build requirements template, connecting the solution of the problem to the information system, standalone requirements management tool or information platform. This step is to find a way to realize the multi-level model in an information system. The final step is to implement the model. We chose two software tools for the implementation, Microsoft Office Excel, a commonly used tool for generating requirements documents, and Siemens PLM suite, Teamcenter, a world leading PLM platform with a requirement module. The results in the study include an auto-injector requirement set, a workflow for using the multi-level model, two requirements templates for implementation of the model in two different software tools, and two automatically generated requirement reports. Our model helps to define the changed part of requirements after analysis of the product change. It could avoid the pitfalls of the current way in reusing requirements. Based on the results from this study, we can draw the following conclusions. A practical multi-level requirements management model can be used for a medical device—the auto-injector; and the model can be implemented into different software tools to support reuse of existing requirement data in creating requirement models for new product development projects. Furthermore, the workflow and guideline to support the application and maintenance of the requirement model can be successful developed and implemented. Requirement documents/reports can be automatically generated through the software tool by following the workflow. And according to our assessment, the multi-level model can improve the reusability of requirements.Item Multimodal Neuroimaging Predictors for Cognitive Performance Using Structured Sparse Learning(Office of the Vice Chancellor for Research, 2013-04-05) Yan, Jingwen; Risacher, Shannon L.; Kim, Sungeun; Simon, Jacqueline C.; Li, Taiyong; Wan, Jing; Wang, Hua; Huang, Heng; Saykin, Andrew J.; Shen, LiRegression models have been widely studied to investigate whether multimodal neuroimaging measures can be used as effective biomarkers for predicting cognitive outcomes in the study of Alzheimer's Disease (AD). Most existing models overlook the interrelated structures either within neuroimaging measures or between cognitive outcomes, and thus may have limited power to yield optimal solutions. To address this issue, we propose to incorporate an L21 norm and/or a group L21 norm (G21 norm) in the regression models. Using ADNI-1 and ADNI-GO/2 data, we apply these models to examining the ability of structural MRI and AV-45 PET scans for predicting cognitive measures including ADAS and RAVLT scores. We focus our analyses on the participants with mild cognitive impairment (MCI), a prodromal stage of AD, in order to identify useful patterns for early detection. Compared with traditional linear and ridge regression methods, these new models not only demonstrate superior and more stable predictive performances, but also identify a small set of imaging markers that are biologically meaningful.Item Nanostructured Molybdenum-Oxide Anodes for Lithium-Ion Batteries: An Outstanding Increase in Capacity(MDPI, 2021) Wang, Hua; Li, Tianyi; Hashem, Ahmed M.; Abdel-Ghany, Ashraf E.; El-Tawil, Rasha S.; Abuzeid, Hanaa M.; Coughlin, Amanda; Chang, Kai; Zhang, Shixiong; El-Mounayri, Hazim; Tovar, Andres; Zhu, Likun; Julien, Christian M.; Mechanical and Energy Engineering, School of Engineering and TechnologyThis work aimed at synthesizing MoO3 and MoO2 by a facile and cost-effective method using extract of orange peel as a biological chelating and reducing agent for ammonium molybdate. Calcination of the precursor in air at 450 °C yielded the stochiometric MoO3 phase, while calcination in vacuum produced the reduced form MoO2 as evidenced by X-ray powder diffraction, Raman scattering spectroscopy, and X-ray photoelectron spectroscopy results. Scanning and transmission electron microscopy images showed different morphologies and sizes of MoOx particles. MoO3 formed platelet particles that were larger than those observed for MoO2. MoO3 showed stable thermal behavior until approximately 800 °C, whereas MoO2 showed weight gain at approximately 400 °C due to the fact of re-oxidation and oxygen uptake and, hence, conversion to stoichiometric MoO3. Electrochemically, traditional performance was observed for MoO3, which exhibited a high initial capacity with steady and continuous capacity fading upon cycling. On the contrary, MoO2 showed completely different electrochemical behavior with less initial capacity but an outstanding increase in capacity upon cycling, which reached 1600 mAh g−1 after 800 cycles. This outstanding electrochemical performance of MoO2 may be attributed to its higher surface area and better electrical conductivity as observed in surface area and impedance investigations.Item Platelets in Alcohol-Associated Liver Disease: Interaction With Neutrophils(Elsevier, 2024) Wang, Juan; Wang, Xianda; Peng, Haodong; Dong, Zijian; Liangpunsakul, Suthat; Zuo, Li; Wang, Hua; Medicine, School of MedicineAlcohol-associated liver disease (ALD) is a major contributor to liver-related mortality globally. An increasing body of evidence underscores the pivotal role of platelets throughout the spectrum of liver injury and recovery, offering unique insights into liver homeostasis and pathobiology. Alcoholic-associated steatohepatitis is characterized by the infiltration of hepatic neutrophils. Recent studies have highlighted the extensive distance neutrophils travel through sinusoids to reach the liver injury site, relying on a platelet-paved endothelium for efficient crawling. The adherence of platelets to neutrophils is crucial for accurate migration from circulation to the inflammatory site. A gradual decline in platelet levels leads to diminished neutrophil recruitment. Platelets exhibit the ability to activate neutrophils. Platelet activation is heightened upon the release of platelet granule contents, which synergistically activate neutrophils through their respective receptors. The sequence culminates in the formation of platelet–neutrophil complexes and the release of neutrophil extracellular traps intensifies liver damage, fosters inflammatory immune responses, and triggers hepatotoxic processes. Neutrophil infiltration is a hallmark of alcohol-associated steatohepatitis, and the roles of neutrophils in ALD pathogenesis have been studied extensively, however, the involvement of platelets in ALD has received little attention. The current review consolidates recent findings on the intricate and diverse roles of platelets and neutrophils in liver pathophysiology and in ALD. Potential therapeutic strategies are highlighted, focusing on targeting platelet–neutrophil interactions and activation in ALD. The anticipation is that innovative methods for manipulating platelet and neutrophil functions will open promising avenues for future ALD therapy.Item Roles of the Site 2 Protease Eep in Staphylococcus aureus(American Society for Microbiology, 2020-07-09) Cheng, Danhong; Lv, Huiying; Yao, Yong; Cheng, Sen; Huang, Qian; Wang, Hua; Liu, Xiaoyun; Bae, Taeok; Li, Min; Liu, Qian; Microbiology and Immunology, School of MedicineIn Enterococcus faecalis, the site 2 protease Eep generates sex pheromones, including cAM373. Intriguingly, in Staphylococcus aureus, a peptide similar to cAM373, named cAM373_SA, is produced from the camS gene. Here, we report that the staphylococcal Eep homolog is not only responsible for the production of cAM373_SA but also critical for staphylococcal virulence. As with other Eep proteins, the staphylococcal Eep protein has four transmembrane (TM) domains, with the predicted zinc metalloprotease active site (HEXXH) in the first TM domain. eep deletion reduced the cAM373_SA activity in the culture supernatant to the level of the camS deletion mutant. It also markedly decreased the cAM373 peptide peak in a high-performance liquid chromatography (HPLC) analysis. Proteomics analysis showed that Eep affects the production and/or the release of diverse proteins, including the signal peptidase subunit SpsB and the surface proteins SpA, SasG, and FnbA. eep deletion decreased the adherence of S. aureus to host epithelial cells; however, the adherence of the eep mutant was increased by overexpression of the surface proteins SpA, SasG, and FnbA. eep deletion reduced staphylococcal resistance to killing by human neutrophils as well as survival in a murine model of blood infection. The overexpression of the surface protein SpA in the eep mutant increased bacterial survival in the liver. Our study illustrates that in S. aureus, Eep not only generates cAM373_SA but also contributes to the survival of the bacterial pathogen in the host.IMPORTANCE The emergence of multidrug-resistant Staphylococcus aureus makes the treatment of staphylococcal infections much more difficult. S. aureus can acquire a drug resistance gene from other bacteria, such as Enterococcus faecalis Intriguingly, S. aureus produces a sex pheromone for the E. faecalis plasmid pAM373, raising the possibility that S. aureus actively promotes plasmid conjugation from E. faecalis In this study, we found that the staphylococcal Eep protein is responsible for sex pheromone processing and contributes to the survival of the bacteria in the host. These results will enhance future research on the drug resistance acquisition of S. aureus and can lead to the development of novel antivirulence drugs.