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Biomedical subjects

Chun Li

Publications and source records attributed to Chun Li.

At least 19 recordsLinked to original sources

Flavoromics-based profiling reveals taste and aroma differences between infant formula and breast milk.

Flavor differences between infant formula (IF) and breast milk (BM) are considered a potential factor affecting infants' acceptance of IF. This experiment employs flavoromics combined with multivariate statistical analysis to systematically compare the flavor profiles of IF and BM. Electronic tongue analysis and amino acid correlation revealed that IF was characterised by pronounced saltiness and umami richness, whereas BM exhibited greater bitterness and astringency. Volatile compound profiling identified five key flavor constituents in IF, predominantly aldehydes such as hexanal and pentanal. In contrast, BM contained a broader array of compounds-including acids, aldehydes, and esters-resulting in a more complex flavor profile. Kyoto Encyclopedia of Genes and Genomes (KEGG)-based metabolic pathway annotation, together with fatty acid profiling, suggested that some volatiles may be associated with lipid oxidation, Maillard reaction and sulfur-containing amino acid degradation pathways, offering a theoretical basis for the targeted optimisation of IF flavor.

Humans↗

UHRF1 restricts HCoV-229E infection through epigenetic silencing of the viral receptor APN.

The emergence of SARS-CoV-2 has posed significant threats to global health, particularly for the older population. Similarly, common human coronaviruses, such as HCoV-229E, which typically cause mild cold-like symptoms, can lead to severe diseases, underscoring the need to understand virus-host interactions and identify host factors contributing to viral pathogenesis and disease progression. In this study, we perform a genome-wide CRISPR knockout screen using HCoV-229E and identify UHRF1 as a potent restriction factor. Mechanistically, UHRF1 suppresses HCoV-229E infection by downregulating the expression of its cell entry receptor, APN, through promoter hypermethylation. Focused CRISPR activation screens of UHRF1-downregulated genes confirm the critical role of APN in HCoV-229E infection and identify additional genes (e.g., SIGLEC1, PLAC8, and heparan sulfate biosynthesis genes) contributing to the restrictive functions of UHRF1. Transcriptomic and single-cell RNA sequencing analysis reveal that UHRF1 expression decreases with age, negatively correlating with increased APN expression. This age-related decline in UHRF1 is validated in primary alveolar macrophages from elderly individuals, which exhibit heightened susceptibility to HCoV-229E compared to those from younger individuals. Our findings highlight UHRF1 as a key age-related host defense factor against coronavirus and provide insights into the epigenetic regulation of viral entry receptors.

Animals↗

Similarity of RNA secondary structures.

In this article, we propose a relatively similar measure to compare RNA secondary structures. We first transform an RNA secondary structure into a special sequence representation. Then, on the basis of symbolic sequence complexity, we obtain the relative distance of RNA secondary structures. The examination of similarities/dissimilarities of a set of RNA secondary structures at the 3'-terminus of different viruses illustrates the utility of the approach.

Base Sequence↗

Beta-1,3-glucan polysaccharide (schizophyllan) acting as a one-dimensional host for creating supramolecular dye assemblies.

We have demonstrated that one-dimensional supramolecular dye assemblies with a uniform diameter can be created by utilizing schizophyllan (SPG) as a one-dimensional host. In the supramolecular nanofibers, the dye molecules are assembled into the different aggregation modes depending on the preparation procedures. The findings establish that SPG is useful for creating the supramolecular nanofibers, where temporal superstructures can be stabilized by the SPG-specific helical higher-order structure. [structure: see text].

Journal Article↗

Comparison between two classes of selective EP(3) antagonists and their biological activities.

Two different series of very potent and selective EP(3) antagonists have been reported: a novel series of ortho-substituted cinnamic acids [Belley, M., Gallant, M., Roy, B., Houde, K., Lachance, N., Labelle, M., Trimble, L., Chauret, N., Li, C., Sawyer, N., Tremblay, N., Lamontagne, S., Carrière, M.-C., Denis, D., Greig, G. M., Slipetz, D., Metters, K. M., Gordon, R., Chan, C. C., Zamboni, R. J. Bioorg. Med. Chem. Lett.2005, 15, 527] and the acylsulfonamides of ortho-(arylmethyl)cinnamates. [(a) Juteau, H., Gareau, Y., Labelle, M., Sturino, C. F., Sawyer, N., Tremblay, N., Lamontagne, S., Carrière, M.-C., Denis, D., Metters, K. M. Bioorg. Med. Chem. 2001, 9, 1977; (b) Juteau, H., Gareau, Y., Labelle, M., Lamontagne, S., Tremblay, N., Carrière, M.-C., Denis, D., Sawyer, N., Metters, K. M. Bioorg. Med. Chem. Lett.2001, 11, 747] The structural differences between the two series, along with their biological activity in vivo, in vitro, and metabolism, are analyzed. Some of those compounds, including hybrids containing the best structural features of both series, possess K(i) as low as 0.6 nM on the EP(3) receptor.

Cinnamates↗

2-D graphical representation for characteristic sequences of DNA and its application.

DNA sequencing has resulted in an abundance of data on DNA sequences for various species. Hence, the characterization and comparison of sequences become more important but still difficult tasks. In this paper, we first give a 2-D ladderlike graphical representation for the characteristic sequences of a DNA sequence, and then construct a 3-component vector, in which the normalized ALE-indices extracted from such three 2-D graphs via D/D matrices are individual components, to characterize the DNA sequence. The examination of similarities/dissimilarities among sequences of the beta-globin genes of different species illustrates the utility of the approach.

Animals↗

[Electrophysiological effects of hyperpolarization activated cyclic nucleotide gated channel 4 overexpression in neonatal cardiomyocytes mediated by recombinant adenovirus].

OBJECTIVE: To explore the electrophysiological effects of hyperpolarization activated cyclic nucleotide gated channel 4 (HCN4) overexpression in rat neonatal cardiomyocytes mediated by recombinant adenovirus. METHODS: Ventricular cardiomyocytes were obtained from 20 neonatal rats. Recombinant adenovirus carrying HCN4 gene, AdHCN4, a dominant isoform of hyperpolarization activated cyclic nucleotide gated cation channel gene in cardiac transduction system, was constructed and used to transfect the neonatal rat ventricular cardiomyocytes. Untransfected cardiomyocytes were used as controls. RT-PCR and immunofluorescence cytochemistry were used to detect the HCN4 mRNA and protein expression. The electrophysiological characteristics of infected cardiomyocytes were studied by patch clamp. RESULTS: The mRNA and protein expression levels of HCN4 in AdHCN4 infected cardiomyocytes were both markedly higher than those of the control cardiomyocytes. AdHCN4 caused a significant increase in The spontaneous rate in the transfected cardiomyocytes was 92.5 + 7.4 bpm, significantly higher than that of the control cells (68.9 + 6.2 bpm, P < 0.05). Patch clamp experiments showed that the pacemaker current density in the AdHCN4 infected cardiomyocytes was 115.7 + 7.8 pA/pF, significantly higher than that of the untransfected cells (7.2 + 0.6 pA/pF, P < 0.05). CONCLUSION: Overexpression of HCN4 can enhance the autorhythmicity of neonatal cardiomyocytes and significantly increase the spontaneous beat rate. HCN4 channel gene may represent a candidate gene in gene therapy for bradycardia diseases.

Action Potentials↗

Identification of a novel in vitro metabonate from liver microsomal incubations.

In vitro drug metabolism studies during the early drug discovery stage are becoming increasingly important. With the increasing demand for high throughput and quick turnaround time for in vitro metabolism studies, however, careful examination of the results and proper design of the experiments are still crucial. In this communication, we report the identification and mechanism of formation of a novel metabonate from incubations of a diamine-containing compound with liver microsomes. The metabonate appeared to be the major product, and its formation was NADPH- and microsomal protein-dependent. Liquid chromatography/mass spectrometry and NMR analysis of the metabonate indicated an extra carbon and unusual formation of an imidazolidine ring. Further studies revealed that this metabonate was not a true biotransformation product from the diamine compound itself in the microsomal incubation, but rather a product resulting from a condensation reaction between the compound and a metabolite of the solvent (alcohol) used in the incubation. When the microsomal incubations contained a small amount of methanol or ethanol as solvent, the alcohols were metabolized to formaldehyde or acetaldehyde, which then condensed with the diamine compound through an imine intermediate to form the metabonate. The compound itself was metabolically stable in vitro when acetonitrile or dimethyl sulfoxide was used as solvent. During the study of in vitro microsomal stability and metabolite identification of amine-containing compounds, the use of alcohol as solvent should be avoided.

Animals↗

An unusual archosaurian from the marine Triassic of China.

A new Triassic archosaurian from China shows a number of aquatic specializations, of which the most striking is the extreme lateral compression of the long tail. Others that may also reflect aquatic adaptations include plate like scapula and coracoid, elongate neck with extremely long and slender ribs, and reduction of osteoderms. In contrast, its pelvic girdle and hind limb have no aquatic modifications. Anatomic features, taphonomy, and local geological data suggest that it may have lived in a coastal-island environment. This lifestyle, convergent with some Jurassic marine crocodyli-forms that lived at least 40 million years later and the saltwater species of extant Crocodylus, contradicts with the prevailing view that Triassic archosaurians were restricted to non-marine ecosystems. Its mosaic anatomy represents a previously unknown ecomorph within primitive archosaurians.

Animals↗

Noncanonical cAMP pathway and p38 MAPK mediate beta2-adrenergic receptor-induced IL-6 production in neonatal mouse cardiac fibroblasts.

We previously reported that cardiac fibroblasts, but not cardiomyocytes, are served as the predominant source of IL-6 after isoproterenol stimulation in mouse myocardium. The present study investigated the molecular mechanism of isoproterenol-mediated secretion of IL-6 in mouse cardiac fibroblasts. Treatment of cells with isoproterenol-induced a time-dependent accumulation of IL-6, which was mediated by beta(2)-adrenergic receptor (AR), the preponderant beta-AR subtype in cardiac fibroblasts. Isoproterenol-induced secretion of IL-6 was mainly mediated by Gs-AC-cAMP signaling cascade and could be negatively regulated by Gi and PI3K. Surprisingly, the effect of cAMP was independent of protein kinase A and the exchange protein directly activated by cAMP (Epac)-Rap1 pathway and suggests the existence of a novel cAMP-dependent mechanism. p38 MAPK inhibitor SB203580, but not extracellular regulated protein kinase inhibitor, abrogated isoproterenol-induced IL-6 release in cardiac fibroblasts and mouse myocardium. Interestingly, p38 MAPK could also be positively regulated by Gs-AC-cAMP but negatively regulated by Gi-PI3K pathway. Finally, multiple transcription factors (AP-1, C/EBP, NF-kappaB and CREB) regulating the IL-6 gene are activated in response to isoproterenol stimulation, which may provide essential linkage between upstream cAMP-p38 MAPK signaling cascade and downstream IL-6 gene transcription. The present results suggest that beta(2)-AR mediates IL-6 production through a noncanonical cAMP responsible pathway and p38 MAPK.

Adrenergic beta-Agonists↗

Variations in the alpha2A-adrenergic receptor gene and their functional effects.

BACKGROUND AND OBJECTIVES: The alpha2A-adrenergic receptor (ADRA2A) plays a central role in the regulation of systemic sympathetic activity and hence cardiovascular responses such as heart rate and blood pressure. The objectives of this study were to systematically search for variants in the ADRA2A gene, to define the gene's haplotype structure, and to examine potential functional effects of these variants. METHODS: We examined 5957 base pairs of contiguous sequence of ADRA2A (promoter, exonic, and 3'-flanking region) using polymerase chain reaction to amplify the genomic target, followed by bidirectional sequencing, in 135 healthy subjects (85 white and 50 black subjects). Haplotypes were inferred by use of an expectation-maximization algorithm. Primary (plasma norepinephrine concentration) and secondary (resting heart rate and blood pressure) phenotypes were compared among subjects grouped by individual polymorphisms and haplotypes. RESULTS: We identified 41 variants, including 24 novel variants. On the basis of 9 optimally selected markers, 11 haplotypes in 5 haplotype groups were inferred, representing approximately 99% of the cohort. Two uncommon variants in complete linkage disequilibrium (G>C at -1903 and C>G at -1607, identified in 3 black subjects) were associated with significantly increased plasma norepinephrine concentrations (376.7 +/- 6.1 pg/mL versus 218.4 +/- 95.0 pg/mL, P = .011). There was no other significant association between genetic variants or any of the haplotypes with phenotypes. CONCLUSION: We describe novel variants and the haplotype structure of the ADRA2A gene. Common genetic ADRA2A variants are not important determinants of baseline cardiovascular measures (plasma norepinephrine, heart rate, and blood pressure) in healthy volunteers.

Adult↗

Haplotype association analysis for late onset diseases using nuclear family data.

In haplotype-based association studies for late onset diseases, one attractive design is to use available unaffected spouses as controls (Valle et al. [1998] Diab. Care 21:949-958). Given cases and spouses only, the standard expectation-maximization (EM) algorithm (Dempster et al. [1977] J. R. Stat. Soc. B 39:1-38) for case-control data can be used to estimate haplotype frequencies. But often we will have offspring for at least some of the spouse pairs, and offspring genotypes provide additional information about the haplotypes of the parents. Existing methods may either ignore the offspring information, or reconstruct haplotypes for the subjects using offspring information and discard data from those whose haplotypes cannot be reconstructed with high confidence. Neither of these approaches is efficient, and the latter approach may also be biased. For case-control data with some subjects forming spouse pairs and offspring genotypes available for some spouse pairs or individuals, we propose a unified, likelihood-based method of haplotype inference. The method makes use of available offspring genotype information to apportion ambiguous haplotypes for the subjects. For subjects without offspring genotype information, haplotypes are apportioned as in the standard EM algorithm for case-control data. Our method enables efficient haplotype frequency estimation using an EM algorithm and supports probabilistic haplotype reconstruction with the probability calculated based on the whole sample. We describe likelihood ratio and permutation tests to test for disease-haplotype association, and describe three test statistics that are potentially useful for detecting such an association.

Age of Onset↗

Dual optical and nuclear imaging in human melanoma xenografts using a single targeted imaging probe.

INTRODUCTION: Dual-labeled imaging agents that allow both nuclear and optical imaging after a single injection would be advantageous in certain applications. In this study, we synthesized and characterized a dual-labeled RGD (Arg-Gly-Asp) peptide and compared nuclear and optical images obtained with this agent. METHODS: 111In-DTPA-Lys(IRDye800)-c(KRGDf) composed of both the 111In chelator diethylenetriaminepentaacetic acid (DTPA) and the near-infrared (NIR) fluorescent dye IRDye800 (excitation/emission, 765/792 nm) was synthesized. The probe was characterized with regard to in vitro biological activity and in vivo pharmacokinetics and the ability to target integrin alphavbeta3. Tumors of mice injected with the dual-labeled probe were imaged both by gamma scintigraphy and NIR fluorescence optical camera. RESULTS: DTPA-Lys(IRDye800)-c(KRGDf), DTPA-Lys-c(KRGDf) and c(KRGDf) inhibited the adhesion of melanoma M21 cells to vitronectin-coated surface with the similar biological activity. Both 111In-DTPA-Lys(IRDye800)-c(KRGDf) and 111In-DTPA-Lys-c(KRGDf) had significantly higher uptakes in alphavbeta3-positive M21 melanoma than in alphavbeta3-negative M21-L melanoma at 4-48 h after their injection. Side-by-side comparison of images obtained using 111In-DTPA-Lys(IRDye800)-c(KRGDf) revealed that in living mice, both optical imaging and gamma scintigraphy enabled noninvasive detection of the bound probe to alphavbeta3-positive tumors, with optical images providing improved resolution and sensitive detection of the superficial lesions and gamma images providing sensitive detection of deeper structures. CONCLUSION: The dual-labeled imaging probe 111In-DTPA-Lys(IRDye800)-c(KRGDf) was found to specifically bind to alphavbeta3 in melanoma tumor cells. Employing both nuclear and optical imaging with a single imaging probe may facilitate translation of NIR fluorescence optical imaging into clinical applications.

Animals↗

Antimetastatic activity of insulin-like growth factor binding protein-3 in lung cancer is mediated by insulin-like growth factor-independent urokinase-type plasminogen activator inhibition.

Insulin-like growth factor binding protein-3 (IGFBP-3), a major IGF-binding protein in human serum, regulates the growth of non-small cell lung cancer (NSCLC) cells through IGF-dependent and IGF-independent mechanisms. However, the role of IGFBP-3 in lung cancer metastasis is not well known. In the present study, we showed that noncytotoxic doses of adenoviral or recombinant IGFBP-3 significantly decreased the migration and invasion of H1299 and A549 NSCLC cells. Furthermore, treatment of human lung fibroblasts with recombinant IGFBP-3 suppressed their ability to stimulate the invasion of H1299 cells. Overexpression of IGFBP-3 markedly reduced lung metastasis of A549 cells in an experimental animal model system and prolonged the survival time of the animals. Urokinase-type plasminogen activator (uPA) inhibitor treatment or uPA small interfering RNA transfection of A549 and H1299 cells resulted in a significant decrease in invasion. Corresponding ELISA, Western blot, gelatin zymogram, and semiquantitative reverse transcription-PCR analyses revealed that IGFBP-3 reduced the expression of uPA mRNA through IGF-independent mechanisms. The specific role of uPA in anti-invasive activity of IGFBP-3 was further confirmed in NSCLC cells, in which uPA expression/activity was suppressed by the transfection with synthetic small interfering RNA or by the treatment with uPA inhibitor or induced by the infection with an adenoviral vector. IGFBP-3 also decreased the expression/activity of matrix metalloproteinase-2 through IGF-dependent but uPA-independent pathways. Taken together, our data suggest that IGFPB-3 effectively block uPA- and matrix metalloproteinase-2-stimulated invasion pathways, ultimately reducing lung cancer cell metastasis. Our findings indicate that IGFBP-3 may be a promising anti-invasive and antimetastatic therapeutic agent in lung cancer.

Animals↗

Silver nanoisland induced synthesis of ZnO nanostructures by vapor phase transport.

ZnO nanostructures including nanorod and nanotower were synthesized on Ag nanoisland coated Si substrate by thermal evaporation and vapor phase transport at atmospheric pressure. The as-prepared ZnO nanorods and nanotowers were single crystal growing along [0001] direction. The growth of ZnO nanostructures strongly depended on the surface morphology of the nanoisland Ag film deposited by electroless nanoelectrochemistry. The growth mechanism of the ZnO nanostructures was proposed on the basis of experimental data. A strong room-temperature photoluminescence in ZnO nanostructures has been demonstrated. The growth technique would be of particular interest for direct integration in the current silicon-technology-based optoelectronic devices.

Crystallization↗

Controllable synthesis of vertically aligned ZnO nanorod arrays in aqueous solution.

High-density well-aligned ZnO nanorod array was successfully synthesized on a large-area magnetron sputtering deposited Al doped ZnO film-coated Si (AZO/Si) substrate via a convenient solution method. X-ray diffraction and scanning electron microscopy show that the nanorods are well-oriented perpendicular to the substrate. The influences of the reaction temperature, time, on the size and shapes of the as-prepared ZnO nanorods (ZNs) samples have been studied. The length and diameter of the nanorods became bigger when a longer reaction time was used. When the temperature is elevated to 130 degrees C, a new conical ZNs was synthesized. Room-temperature photoluminescence (PL) spectra of all the ZnO products showed a strong ultraviolet (UV) emission. The photoluminescence from free excitons of the ZNs synthesized at higher temperature reflects the high purity and nearly defect free structure of nanorods. The well-aligned feature of the nanorod array is attributed to the nanorods' epitaxial growth from the AZO films.

Crystallization↗

The antimelanoma immunocytokine scFvMEL/TNF shows reduced toxicity and potent antitumor activity against human tumor xenografts.

The immunocytokine scFvMEL/TNF, a fusion protein composed of human tumor necrosis factor (TNF) and a single-chain Fv antibody (scFv) scFvMEL targeting the melanoma gp240 antigen, demonstrates impressive cytotoxic effects against human melanoma cell lines in vitro. Pharmacokinetic studies of 125I-scFvMEL/TNF in BALB/c mice showed that the construct clears from the circulation with a terminal-phase half-life of 17.6 hours after intravenous administration. The maximum tolerated dose of scFvMEL/TNF in nude mice was 4 mg/kg, i.v., on a daily x5 schedule. There were no changes in gross pathology, clinical chemistry, or hematologic parameters in mice treated at doses of up to 3 mg/kg. Therapeutic studies at a dose of 2.5 mg/kg on athymic mice bearing established (approximately 50 mm3) human melanoma A375GFP xenograft tumors transfected with green fluorescent protein demonstrated potent tumor suppression and complete tumor regression of all lesions. There was no subsequent outgrowth of tumors from mice rendered tumor-free. These data show that scFvMEL/TNF can target melanoma cells in vivo and can result in pronounced antimelanoma effects after systemic administration. Toxicology studies indicate the relative safety of this agent at doses that are therapeutically effective and provide guidance to projected phase I starting doses on patients at this schedule.

Animals↗