Publications by authors named "Changhua Shi"

Alzheimer's disease (AD), a chronic and progressive neurodegenerative disease, is characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. Conventional anti-AD drugs exhibit high toxicity and adversely impact patients' quality of life. Therefore, novel treatments for AD are urgently required.

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Intein-mediated protein splicing has been widely used in protein engineering; however, the splicing efficiency and extein specificity usually limit its further application. Thus, there is a demand for more general inteins that can overcome these limitations. Here, we study the -splicing of CPE intein obtained from the directed evolution of PRP8, which shows that its splicing rate is ~29- higher than that of the wild-type.

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Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease worldwide and is the main microvascular complication of diabetes. The increasing prevalence of diabetes has increased the need for effective treatment of DKD and identification of new therapeutic targets for better clinical management. Mitophagy is a highly conserved process that selectively removes damaged or unnecessary mitochondria the autophagic machinery.

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A purification system was constructed with the N-segment of the Npu DnaE split intein as an affinity ligand immobilized onto an epoxy-activated medium and the C-segment used as the cleavable tag fusing target protein. The affinity properties of C-tagged proteins adsorbed on I affinity chromatography medium were studied with GFP as a model target protein. The saturated adsorption capacity and dynamic adsorption capacity reached 51.

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There is solid evidence that haze pollution threatens human health owing to the abiotic pollutants it contains. However, the characteristics of airborne bacterial communities in indoor and outdoor environments exhibiting haze occurrence are still unknown. Thus, we examined variations in both indoor and outdoor airborne bacterial communities in Beijing from December 9-27, 2016, a period which included three haze events.

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Replicative DNA polymerases are highly efficient enzymes that maintain stringent geometric control over shape and orientation of the template and incoming nucleoside triphosphate. In a surprising twist to this paradigm, a naturally occurring bacterial DNA polymerase I member isolated from Geobacillus stearothermophilus (Bst) exhibits an innate ability to reverse transcribe RNA and other synthetic congeners (XNAs) into DNA. This observation raises the interesting question of how a replicative DNA polymerase is able to recognize templates of diverse chemical composition.

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Aim: This study aims to explore the similarity and difference of hippocampal miRNAomes between humans and mice.

Materials & Methods: A systematic comparison of the miRNAomes between healthy human and mouse hippocampi was performed using high-throughput sequencing followed by bioinformatic analyses.

Results: A novel miRNA termed novel-21-5p and a human-specific miR-656-3p were identified in human hippocampi, which were expressed ubiquitously and predicted to be associated with neural activities.

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In this work, we describe a novel self-cleaving tag technology based on a highly modified split-intein cleaving element. In this system, the N-terminal segment of an engineered split intein is expressed in E. coli and covalently immobilized onto a capture resin, while the smaller C-terminal intein segment is fused to the N-terminus of the desired target protein.

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Darwinian evolution experiments carried out on xeno-nucleic acid (XNA) polymers require engineered polymerases that can faithfully and efficiently copy genetic information back and forth between DNA and XNA. However, current XNA polymerases function with inferior activity relative to their natural counterparts. Here, we report five X-ray crystal structures that illustrate the pathway by which α-(L)-threofuranosyl nucleic acid (TNA) triphosphates are selected and extended in a template-dependent manner using a laboratory-evolved polymerase known as Kod-RI.

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The topic of gut microbiota is currently attracting considerable interest as a potential factor in Alzheimer's disease (AD). However, the extent and time course of alterations in the gut microbiota, and their effects on AD pathology remain uncertain. Herein, we compared the fecal microbiomes and fecal short chain fatty acid composition (SCFAs) between wild-type and AD model mice at different ages under strictly controlled specific pathogen free conditions, and also conducted microscopic investigations of intestinal structures.

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Threose nucleic acid (TNA) is an artificial genetic polymer capable of undergoing Darwinian evolution to produce aptamers with affinity to specific targets. This property, coupled with a backbone structure that is refractory to nuclease digestion, makes TNA an attractive biopolymer system for diagnostic and therapeutic applications. Expanding the chemical diversity of TNA beyond the natural bases would enable the development of functional TNA molecules with enhanced physiochemical properties.

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Long non-coding RNAs (lncRNAs), which are long transcripts without apparent protein-coding roles, interfere with gene expression and signaling events at various stages. Increasing evidence has suggested that lncRNAs function in the regulation of tissue homeostasis and under pathophysiologic conditions. In the nervous system, the expression of lncRNAs has been detected and characterized under normal physiologic conditions and in disease states.

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Spider silk is an attractive biopolymer with numerous potential applications due to its remarkable characteristics. Among the six categories of spider silks, flagelliform (Flag) spider silk possesses longer and more repetitive core domains than others, therefore performing the highest extensibility. To investigate the correlation between the recombinant spidroin size and the synthetic fiber properties, four recombinant proteins with different sizes [N-Scn-C (=1-4)] were constructed and expressed using IMPACT system.

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Fusions of elastin-like peptide (ELP) purification tags and self-cleaving inteins provide a powerful platform for purifying tagless recombinant proteins without the need for conventional packed-bed columns. A drawback to this method has been premature cleaving of the ELP tag during expression, before the purification procedure can take place. Here we demonstrate a split-intein method, where the self-cleaving intein is divided into two inactive segments during expression and purification.

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Background: Phloroglucinol plays an important role in oxidative stress and inflammatory responses. The effects of phloroglucinol have been proven in various disease models. The aim of the present study was to investigate the efficacy and possible mechanisms of phloroglucinol in the treatment of interstitial cystitis (IC).

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Many important functional proteins often exhibit toxicity when overexpressed in heterologous hosts. Unfortunately, this toxicity can complicate the production of these proteins in recombinant systems, which can slow their characterization. Although a number of engineered expression strains and plasmids have been developed to optimize toxic protein expression, many targets remain recalcitrant in these systems due to extreme toxicity to the expression host.

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Mutations in thyroid hormone receptors (TRs) often lead to metabolic and developmental disorders, but patients with these mutations are difficult to treat with existing thyromimetic drugs. In this study, we analyzed six clinically observed mutations in the ligand-binding domain of the human TRβ using an engineered bacterial hormone biosensor. Six agonist compounds, including triiodothyronine (T3), thyroxine (T4), 3,5,3'-triiodothyroacetic acid (Triac), GC-1, KB-141, and CO-23, and the antagonist NH-3 were examined for their ability to bind to each of the TRβ mutants.

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Self-cleaving elastin-like protein (ELP) tags provide a very promising tool for recombinant protein purification. With this method, the target protein is purified by simple ELP-mediated precipitation steps, followed by self-cleavage and removal of the ELP tag. Unfortunately, however, inteins usually experience some level of pre-cleavage during protein expression, which can significantly decrease final yields.

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Human choriocarcinoma is one of the most aggressive malignant tumors characterized by early hematogenous spread to lung and brain tissues, and may be a cause of death in patients. Choriocarcinoma may occur following pregnancy and during implantation; however, trophoblastic invasion in human pregnancy is tightly regulated. The transforming growth factor-beta 1 (TGF-β1) has been suggested to play a role in controlling this process.

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In this study, we investigated the effects of mobile phone radiation on spatial learning, reference memory, and morphology in related brain regions. After the near-field radiation (0.52-1.

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Gestational trophoblastic disease (GTD) is a unique disease that arises from allografting of the conceptus, and has a characteristic morphology and biological behavior. It encompasses a spectrum of interrelated diseases, including hydatidiform mole, invasive mole, choriocarcinoma and placental-site trophoblastic tumor, but its pathogenesis remains unrevealed. Particularly, choriocarcinoma is a highly malignant tumor with poor prognosis.

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Molecularly imprinted solid-phase extraction (MISPE) combined with HPLC were used to detect trace 17β-estradiol (E2) in different dairy and meat samples. E2 imprinted mono-dispersed microspheres prepared by modified precipitation polymerisation method were used as MISPE sorbents. Under optimum MISPE and HPLC conditions, trace (0.

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Aim: To evaluate the effects of electromagnetic irradiation of 2000 μW/cm(2); exposure on mRNA and protein expression levels of immunoreactive protein and mRNA of NMDA receptor 2A subunit in rats hippocampal, and to explore the mechanism of electromagnetic irradiation induced learning and memory impairment.

Methods: Rats were randomly divided into normal control group, sham-radiated group, and 1 h/d, 2 h/d, and 3 h/d radiation groups. The rats in the radiation groups were fixed after microwave exposure of 2000 μW/cm(2);, then their learning and memory abilities were tested by Morris water maze experiment, the change of NR2A protein in hippocampal neurons of each group of rats were measured with immunohistochmistry and Western blot techniques, and the expression of NR2A mRNA in hippocampus were determined by RT-PCR.

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Bisphenol A (BPA)-imprinted polymeric microspheres were synthesized by modified precipitation polymerization (MPP) method. Influences of cross-linker, monomer, porogen volume, and agitation on polymerization were investigated. Proper amount of cross-linker ethyleneglycol-dimethacrylate (EGDMA) was critical to achieve narrowly dispersed microspheres.

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Objective: To study the dose-response relation of the fish drugs and their joint toxicity on the luminescent bacteria.

Methods: The single and joint toxicity of four kinds of fish drugs were inspected and evaluated by applying luminescent bacteria toxicity test. RESULTS; Four chemical componds were negatively correlated with luminescence and all correlation coefficient were greater than 0.

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