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Biomedical subjects

Wei Sun

Publications and source records attributed to Wei Sun.

At least 19 recordsLinked to original sources
PubMed2026

Targeting the F17-A Fimbrial gene: An efficient method for the quantitative detection of Escherichia coli F17.

Escherichia coli (E. coli) F17 is one of the leading bacterial causes of diarrhea in farm livestock, which cause huge economic losses and could also pose potential risks to public health. Generally, the monitoring the E. coli F17 is based on the polymerase chain reaction (PCR) and bacteria plate counting method, which were largely limited by the time-consuming nature and susceptibility to detection errors. Hence, there is an urgent need to develop a rapid and quantitative detection method for E. coli F17. In the present study, an E. coli F17 challenge experiment in ovine intestinal epithelial cells (IECs) was employed as an in vitro model. At different post-challenge time points (1 h, 2 h, and 3 h), two conventional methods (bacteria plate counting and microplate method) were conducted as benchmarks to estimate the number of E. coli F17 adhering to the IECs. Additionally, total genomic DNA was extracted and quantitative Real-time PCR (qPCR) was performed to detect the relative abundance of E. coli F17 fimbrial pilin (F17-A) and adhesion (F17-G) genes. Subsequently, statistical analyses, including Pearson's correlation coefficient (PCC) method and linear curve-fitting, were performed to evaluate the correlation between the abundance of F17-A/G genes and the results of the benchmark methods. The results showed that the relative abundances of both genes were highly correlated with the number of E. coli F17 that adhered to the IECs, among them, the F17-A gene showed a stronger correlation with the bacterial counts, exhibiting a correlation coefficient > 0.85. Furthermore, standard curves analyses further confirmed the out-performed quantitative performance of F17-A gene and a significantly stronger correlation with bacterial counts which exhibited an outstanding linear correlation (r = -0.9534, R2 = 0.9252) with amplification efficiency of 101.4%, The results of the present study indicate that targeting fimbrial genetic hallmarks via qPCR is an effective and promising method for E. coli F17 quantification, which could potentially contribute to epidemiological studies and pathogen monitoring in the livestock industry.

Detection↗
PubMed2026

Decoding sequence recognition code of nucleic acid-binding proteins of human-infecting DNA viruses.

Human-infecting DNA viruses remain major health threats, yet the DNA-recognition mechanisms of their nucleic acid-binding proteins (NBPs) are poorly understood. Here, we systematically profiled 103 viral NBPs from human-infecting DNA viruses, with three NBPs from non-human-infecting DNA viruses as controls, using high-throughput screening. This analysis identified diverse DNA-binding motifs and specificity modules, including convergent recognition of a conserved CCACC motif across phylogenetically distant viruses. Notably, viral NBP binding-site distributions varied with genome size, and several NBPs from small-genome viruses showed enrichment on mitochondrial DNA. Functional assays further supported their mitochondrial association and effects on mitochondrial membrane potential. By integrating an ivTRT-based ssDNA-SELEX workflow, we further found that ssDNA viral NBPs recognize dimer-like and inverted-repeat sequences with potential to form stem-loop structures. Collectively, this study constructs a comprehensive viral NBP DNA-recognition atlas, offering a fundamental resource for elucidating viral genome recognition mechanisms, virus-mitochondria interactions, and developing future antiviral strategies.

Letter↗
PubMed2025

Hierarchical integration of mNGS, PCR, and other conventional methods for precision TB diagnostics.

UNLABELLED: This study systematically compared the diagnostic accuracy of seven assays for detecting the Mycobacterium tuberculosis complex, including metagenomic next-generation sequencing (mNGS), droplet digital polymerase chain reaction, real-time quantitative polymerase chain reaction, EasyNAT MTC, GeneXpert MTB/RIF, interferon-gamma release assay (IGRA), and acid&#x2012;fast staining (AFS). We try to select appropriate combinations of tuberculosis (TB) detection methods for regions with varying levels of medical resources, based on sensitivity, cost-effectiveness, and operational feasibility. A retrospective analysis was conducted on 141 samples collected from patients with suspected active TB at The First Affiliated Hospital of Sun Yat-sen University between April 2022 and April 2024. Among these samples, there were 100 cases assigned to the case group and 41 cases to the control group, based on the tuberculosis diagnostic criteria. Historical data for Xpert, IGRA, and AFS were collected, and parallel experiments using mNGS, droplet digital PCR (ddPCR), real-time quantitative polymerase chain reaction (RT-qPCR), and EasyNAT were conducted on all samples. Diagnostic performance was evaluated by comparing it with the final clinical diagnoses. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic (ROC) curve analysis were conducted, along with DeLong tests for statistical comparison. Compared with the final clinical diagnosis, mNGS demonstrated the highest sensitivity (100%), followed by IGRA (79.2%), EasyNAT (79.1%), RT-qPCR (78.0%), ddPCR (75.8%), Xpert (75.3%), and AFS (16.7%). The specificity was 100% for both Xpert and AFS, followed by ddPCR (97.6%), RT-qPCR (95.1%), EasyNAT (92.7%), IGRA (72.7%), and mNGS (75.6%). ROC analysis revealed a significantly greater area under the ROC curve for mNGS (0.878) than for ddPCR (0.817, P = 0.031). DeLong tests revealed statistically significant differences in diagnostic performance between mNGS and ddPCR (P < 0.05) and between IGRA and AFS (P < 0.01). mNGS uniquely identified the pathogens involved in co-infection and quantified pathogen-specific sequencing reads. Through a comprehensive evaluation of the diagnostic efficacy, cost-effectiveness, and timeliness of tuberculosis detection methods, we propose corresponding combinations of TB testing approaches for regions with different healthcare resources. For undeveloped regions with limited resources, a combination of AFS +EasyNAT + chest X-ray is recommended. Primary care facilities may additionally employ IGRA + RT-qPCR. Intermediate-level hospitals can incorporate Xpert MTB/RIF for drug resistance testing, while tertiary hospitals or specialized centers should, on the basis of these fundamental tests, utilize mNGS for diagnosis and ddPCR for therapeutic monitoring in patients with complex mixed infections. IMPORTANCE: This study is the first to comprehensively evaluate the diagnostic efficacy, cost-effectiveness, and timeliness of seven TB detection methods in a single-center cohort. Our findings provide actionable solutions for optimizing TB diagnostics in diverse healthcare ecosystems, aligning with the WHO's End TB Strategy to ensure equitable access to rapid diagnostics.

Humans↗
PubMed2024

Gut microbial genomes with paired isolates from China illustrate probiotic and cardiometabolic effects.

The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we present the Chinese Gut Microbial Reference (CGMR) set, comprising 101,060 high-quality metagenomic assembled genomes (MAGs) of 3,707 nonredundant species from 3,234 fecal samples across primarily rural Chinese locations, 1,376 live isolates mainly from lactic acid bacteria, and 987 novel species relative to worldwide databases. We observed region-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. Preliminary mouse experiments suggest a probiotic effect of two Faecalibacillus intestinalis isolates in alleviating constipation, cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and isolates from the genera Parabacteroides and Lactobacillus in host lipid metabolism. Our study expands the current microbial genomes with paired isolates and demonstrates potential host effects, contributing to the mechanistic understanding of host-microbe interactions.

Probiotics↗
PubMed2007

Investigation on the transition crystal of ordinary rutile TiO2 powder by microwave irradiation in hydrogen peroxide solution and its sonocatalytic activity.

The transition crystal TiO(2) catalyst with high sonocatalytic activity was obtained utilizing the microwave irradiation in hydrogen peroxide solution. At the same time a series of affecting factors (microwave irradiation time, heat-treated time and heat-treated temperature) to prepare the TiO(2) catalyst on the sonocatalytic degradation of parathion were considered in this paper. The ultrasound of low power was used as an irradiation source to induce treated TiO(2) particles to perform catalytic activity. The results show that the sonocatalytic activity of the transition crystal TiO(2) powder is obviously higher than those of pure ordinary rutile and anatase TiO(2) powders. At last, the parathion in aqueous solution was degraded completely and became some simple inorganic ions such as NO(3)(-), PO(4)(3-), SO(4)(2-), etc. The degradation ratio of parathion in the presence of the transition crystal TiO(2) catalyst attains nearly 80% within 60 min ultrasonic irradiation, while corresponding ones are only 65.23% and 53.88%, respectively, for pure ordinary rutile and anatase TiO(2) powders.

Journal Article↗
PubMed2006

Statins activate AMP-activated protein kinase in vitro and in vivo.

BACKGROUND: Statins exert pleiotropic effects on the cardiovascular system, in part through an increase in nitric oxide (NO) bioavailability. AMP-activated protein kinase (AMPK) plays a central role in controlling energy and metabolism homeostasis in various organs. We therefore studied whether statins can activate AMPK, and if so, whether the activated AMPK regulates nitric oxide (NO) production and angiogenesis mediated by endothelial NO synthase, a substrate of AMPK in vascular endothelial cells. METHODS AND RESULTS: Western blotting of protein extracts from human umbilical vein endothelial cells treated with atorvastatin revealed increased phosphorylation of AMPK at Thr-172 in a time- and dose-dependent manner. The AMPK activity, assessed by SAMS assay, was also increased accordingly. The phosphorylation of acetyl-CoA carboxylase at Ser-79 and of endothelial NO synthase at Ser-1177, 2 putative downstream targets of AMPK, was inhibited by an adenovirus that expressed a dominant-negative mutant of AMPK (Ad-AMPK-DN) and compound C, an AMPK antagonist. The positive effects of atorvastatin, including NO production, cGMP accumulation, and in vitro angiogenesis in Matrigel, were all blocked by Ad-AMPK-DN. Mice given atorvastatin through gastric gavage showed increased AMPK, acetyl-CoA carboxylase, and endothelial NO synthase phosphorylation in mouse aorta and myocardium. CONCLUSIONS: Statins can rapidly activate AMPK via increased Thr-172 phosphorylation in vitro and in vivo. Such phosphorylation results in endothelial NO synthase activation, which provides a novel explanation for the pleiotropic effects of statins that benefit the cardiovascular system.

AMP-Activated Protein Kinases↗
PubMed2006

Altered expression of vasoactive intestinal peptide receptors in T lymphocytes and aberrant Th1 immunity in multiple sclerosis.

Vasoactive intestinal peptide (VIP) has a unique property of regulating T(h)1 and T(h)2 immunity of CD4+ T cells. In this study, we demonstrated, for the first time, that differential expression of VIP receptors and a compensatory mechanism directly affect the responsiveness of CD4+ T cells and their T(h)1 and T(h)2 properties to VIP. The expression of VIP receptor-1 (VPAC1) and VPAC2 in CD4+ T cells changed reciprocally in the context of the activation state. In activated CD4+ T cells of healthy individuals, markedly decreased VPAC1 expression was compensated for by increased expression of VPAC2 induced by T cell activation. In contrast, there was altered expression of VPAC2 in activated CD4+ T cells derived from multiple sclerosis (MS) patients, which rendered CD4+ T cells less responsive to VIP and skewed the system to a predominantly in a T(h)1 direction. Detailed characterization with agonist peptides of VIP showed that residues Met and Ser at positions 17 and 25 of VIP were critical to its regulatory properties through interaction with VAPC2. Furthermore, altered levels of VPAC2 expression in T cells of MS patients were not associated with single-nucleotide polymorphism in the encoding region of the VPAC2 gene but with gene regulation as characterized by a distinct DNA footprinting pattern in the promoter region of the VPAC2 gene in MS as compared with controls. This study has provided new evidence for an intrinsic mechanism associated with an aberrant, pro-inflammatory state of CD4+ T cells in MS.

Adult↗
PubMed2006

Characterization of the Rana grylio virus 3beta-hydroxysteroid dehydrogenase and its novel role in suppressing virus-induced cytopathic effect.

The 3beta-hydroxysteroid dehydrogenase (3beta-HSD) isoenzymes play a key role in cellular steroid hormone synthesis. Here, a 3beta-HSD gene homolog was cloned from Rana grylio virus (RGV), a member of family Iridoviridae. RGV 3beta-HSD gene has 1068bp, encoding a 355aa predicted protein. Transcription analyses showed that RGV 3beta-HSD gene was transcribed immediate-early during infection from an initiation site 19 nucleotides upstream of the translation start site. Confocal microscopy revealed that the 3beta-HSD-EGFP fusion protein was exclusively colocalized with the mitochondria marker (pDsRed2-Mito) in EPC cells. Upon morphological observation and MTT assay, it was revealed that overexpression of RGV 3beta-HSD in EPC cells could apparently suppress RGV-induced cytopathic effect (CPE). The present studies indicate that the RGV immediate-early 3beta-HSD gene encodes a mitochondria-localized protein, which has a novel role in suppressing virus-induced CPE. All these suggest that RGV 3beta-HSD might be a protein involved in host-virus interaction.

Amino Acid Sequence↗
PubMed2006

Spectroscopic, viscositic and electrochemical studies of DNA interaction with a novel mixed-ligand complex of nickel (II) that incorporates 1-methylimidazole and thiocyanate groups.

A novel mixed-ligand nickel(II) complex that contains 1-methylimidazole and thiocyanate, Ni(NCS)(2)(Mim)(4) (Mim=1-methylimidazole), was synthesized and its structure was determined by X-ray crystallography, IR spectrum and elemental analysis, etc. Its DNA-binding properties were studied by electronic absorption spectral, viscositive and electrochemical measurements. The absorption spectral and viscositive results suggest that the nickel(II) complex binds to DNA via partial intercalation. The addition of DNA results in the decrease of the peak current of the nickel(II) complex proved their interaction. The slight differences of peak profiles and electrochemical parameters between free and DNA-bound Ni(NCS)(2)(Mim)(4) showed the formation of an electrochemical inactive complex between Ni(NCS)(2)(Mim)(4) and DNA. The binding site and binding constant of the complex to DNA were determined by electrochemical titration method.

Animals↗
PubMed2006

Regulation of Stat3 transcriptional activity by the conserved LPMSP motif for OSM and IL-6 signaling.

To achieve maximal transcriptional activity in response to gp130 cytokines, Serine-727 (Ser-727) of Stat3 is phosphorylated. Ser-727 resides in the LPMSP motif, the only conserved sequence among the transcription activation domains of several STATs. We show here that in addition to Ser-727, other residues in this LPMSP motif are also required for Stat3 activity in response to cytokine signaling through regulation of Ser-727 phosphorylation and recruitment of the transcription co-activator CBP/p300 to the promoters of Stat3-target genes for transcription activation. Hence, we have demonstrated a critical role for the whole conserved LPMSP motif in JAK-STAT signaling.

Amino Acid Motifs↗
PubMed2006

Effects of nimodipine, an L-type calcium channel antagonist, on the chicken's cochlear potentials.

At most synapses in the brain, neurotransmitter release depends on N-type or P/Q-type calcium channels. However, available in vitro experimental data suggest that there exist almost exclusively L-type calcium channels in sensory hair cells of most species. To test whether chicken hair cells depend on L-type calcium channels for neurotransmitter release, we examined the effects of nimodipine, a selective L-type calcium channel antagonist, on acoustically evoked cochlear potentials in 10-15 week old chickens in vivo. Diffusion of nimodipine into scala tympani significantly elevated threshold, dramatically decreased the amplitude and increased the latency of the compound action potential within 20 min of drug application. The summating potential was also significantly reduced in amplitude, but the cochlear microphonic was relatively less affected. All the effects were reversible after nimodipine was washed out with artificial perilymph except that the cochlear microphonic amplitude remained decreased. Application of omega-conotoxin GVIA, an N-type calcium channel antagonist and agatoxin Tk, a P-type calcium channel antagonist had no observable effects on the cochlear potentials. These results suggest that L-type calcium channels control neurotransmitter release from avian hair cells.

Action Potentials↗
PubMed2006

A gradient HPLC method for the quality control of chlorogenic acid, linarin and luteolin in Flos Chrysanthemi Indici suppository.

The Flos Chrysanthemi Indici suppository, a famous traditional Chinese medicine, is marketed for the treatment of prostatitis and chronic pelvic inflammation. A simple, relatively rapid and accurate high-performance liquid chromatographic (HPLC) method was applied to the simultaneous determination of chlorogenic acid, linarin and luteolin in Flos Chrysanthemi Indici suppository. The good separation was achieved on a Hypersil ODS column by a gradient elution using the mixture of acetonitrile and aqueous 1.0% acetic acid as mobile phase within 23 min. The method was validated for three active phenolic compounds with the relative standard deviations (R.S.D.) of intra- and inter-day precision below 3.0%, and the detection limits (S/N=3) of chlorogenic acid, linarin and luteolin were 0.32, 0.08 and 0.05 microg ml(-1), respectively. This assay was successfully applied to the determination of three active phenolic compounds in Flos Chrysanthemi Indici suppository samples with the quantitative recoveries in the range of 94.7-101.8%. The results indicate that the developed HPLC method can be readily utilized as a quality control method for Flos Chrysanthemi Indici suppository and its related traditional Chinese medicinal preparations.

Acetic Acid↗
PubMed2006

Expression and significance of ICAM-1 and its counter receptors LFA-1 and Mac-1 in experimental acute pancreatitis of rats.

AIM: To investigate the role of intercellular adhesion molecule-1 (ICAM-1) and its counter receptors LFA-1 and Mac-1 in acute pancreatitis (AP). METHODS: SD rats were allocated to AP group and control group randomly (25 rats each). AP was induced by infusion of 5% chenodeoxycholic acid into the pancreatic duct, followed by ligation of pancreatic duct. The rats were sacrificed at 1, 3, 6, 12 and 24 h after induction of pancreatitis. Five rats were sacrificed at one time point in the two groups before the blood and specimens from pancreas and lung were obtained. Serum amylase and ascitic fluid were measured at each time point. Expression of ICAM-1 at different time points was assessed by immunohistochemistry in pancreas and lung, and the expression of LAF-1 and Mac-1 on neutrophils at different time points was detected by flow cytometer. RESULTS: Induction of AP was confirmed by the serum levels of amylase and histological studies. The expression of ICAM-1 in pancreas increased significantly than that in the control group at all time points (P<0.05 or P<0.01), as well as the expression in lung except at 1 h. The expression of LFA-1 and Mac-1 on neutrophil in blood increased significantly in AP group than that in control group at several time points (P<0.05 or P<0.01). The amount of ascitic fluid and serum amylase level of AP group increased significantly than that of control group at all time points (P<0.05 or P<0.01). Parallel to these results, a significant neutrophil infiltration was found in pancreas and lung tissues of AP group rats. CONCLUSION: Our findings suggest the important role for ICAM-1, LFA-1 and Mac-1 in mediating the development of AP from a local disease to a systemic illness. Upregulation of ICAM-1, LFA-1, Mac-1 and subsequent leukocyte infiltration appear to be significant events of pancreatic and pulmonary injuries in AP.

Acute Disease↗
PubMed2006

Salicylate induced tinnitus: behavioral measures and neural activity in auditory cortex of awake rats.

Neurophysiological studies of salicylate-induced tinnitus have generally been carried out under anesthesia, a condition that abolishes the perception of tinnitus and depresses neural activity. To overcome these limitations, measurement of salicylate induced tinnitus were obtained from rats using schedule induced polydipsia avoidance conditioning (SIPAC) and gap pre-pulse inhibition of acoustic startle (GPIAS). Both behavioral measures indicated that tinnitus was present after treatment with 150 and 250 mg/kg of salicylate; measurements with GPIAS indicated that the pitch of the tinnitus was near 16 kHz. Chronically implanted microwire electrode arrays were used to monitor the local field potentials and spontaneous discharge rate from multiunit clusters in the auditory cortex of awake rats before and after treatment with 150 mg/kg of salicylate. The amplitude of the local field potential elicited with 60 dB SPL tone bursts increased significantly 2h after salicylate treatment particularly at 16-20 kHz; frequencies associated with the tinnitus pitch. Field potential amplitudes had largely recovered 1-2 days post-salicylate when behavioral results showed that tinnitus was absent. The mean spontaneous spike recorded from the same multiunit cluster pre- and post-salicylate decreased from 22 spikes/s before treatment to 14 spikes/s 2h post-salicylate and recovered 1 day post-treatment. These preliminary physiology data suggest that salicylate induced tinnitus is associated with sound evoked hyperactivity in auditory cortex and spontaneous hypoactivity.

Animals↗
PubMed2006

Role of IFN-gamma in induction of Foxp3 and conversion of CD4+ CD25- T cells to CD4+ Tregs.

IFN-gamma is an important Th1 proinflammatory cytokine and has a paradoxical effect on EAE in which disease susceptibility is unexpectedly heightened in IFN-gamma-deficient mice. In this study, we provide what we believe is new evidence indicating that IFN-gamma is critically required for the conversion of CD4+ CD25- T cells to CD4+ Tregs during EAE. In our study, the added severity of EAE in IFN-gamma knockout mice was directly associated with altered encephalitogenic T cell responses, which correlated with reduced frequency and function of CD4+ CD25+ Foxp3+ Tregs when compared with those of WT mice. It was demonstrated in both human and mouse systems that in vitro IFN-gamma treatment of CD4+ CD25- T cells led to conversion of CD4+ Tregs as characterized by increased expression of Foxp3 and enhanced regulatory function. Mouse CD4+ CD25- T cells, when treated in vitro with IFN-gamma, acquired marked regulatory properties as evidenced by suppression of EAE by adoptive transfer. These findings have important implications for the understanding of the complex role of IFN-gamma in both induction and self regulation of inflammatory processes.

Amino Acid Sequence↗
PubMed2006

Age-related smoking progression among adolescents in China.

PURPOSE: This study examined the differences in smoking progression between middle and upper school students. METHODS: The China Seven Cities Study (CSCS) is a longitudinal cohort study. The current sample consists of subjects with both baseline and one-year follow-up measures collected between October 2002 and December 2003. There were 4842 students from 62 middle schools and 5806 students from 83 upper schools. Multilevel random-coefficient modeling techniques were applied. RESULTS: Among male never or lifetime ever smokers, middle school students were susceptible to transitioning more rapidly than upper school students (never--RR: 1.272, 95% confidence interval [CI]: .985-1.642; lifetime ever--RR: 1.497, 95% CI: .979-2.290). Among female lifetime ever smokers, middle school students were more likely to progress than upper school students (RR: 1.353, 95% CI: 1.038-1.763). CONCLUSION: This longitudinal study is the first to explore differences in smoking progression among adolescents in China. The results revealed that over a one-year interval, there was greater progression across smoking trajectories during early adolescence (corresponding to middle school) than later adolescence (upper school). This is consistent with the neurological development hypothesis, but does not rule out alternative explanations. These findings are important to consider relative to the content and timing of prevention interventions in China where smoking rates approach 70% in adult males and are increasing rapidly in women.

Adolescent↗
PubMed2006

Cerebral acetylcholine and choline contents and turnover following low-dose acetylcholinesterase inhibitors treatment in rats.

Male Sprague-Dawley rats were treated for 3 weeks with (1) regular tap drinking water plus subcutaneous (s.c.) saline (0.5 ml/kg) injections three times/week, (2) pyridostigmine bromide (PB) in drinking water (80 mg/L) plus s.c. saline injections three times/week, (3) regular tap drinking water plus s.c. sarin (0.5 x LD(50)) injections three times/week, or (4) PB in drinking water plus s.c. sarin injections three times/week. Repeated doses of sarin, in the presence or absence of PB, were devoid of acute toxicity during the three-week treatment period. Two, 4, and 16 weeks post-treatment, animals were given an intravenous pulse injection of choline labeled with 4 deuterium atoms (D4Ch) followed, after 1 min, by microwave fixation of the brain in vivo. Tissue levels of endogenous acetylcholine (D0ACh), endogenous choline (D0Ch), D4Ch, and ACh synthesized from D4Ch (D4ACh) were measured by gas-chromatography mass-spectrometry in hippocampus, infundibulum, mesencephalon, neocortex, piriform cortex, and striatum. Ch uptake from blood and ACh turnover were estimated from D4Ch and D4ACh concentrations in brain tissue, respectively. Statistically significant differences among brain regions were found for D0Ch, D4Ch, D0ACh and D4ACh at 2, 4 and 16 weeks post-treatment. However, differences in the values of these parameters between control and drug treatments were found only for D0ACh and D0Ch at 2 and 4 weeks, but not at 16 weeks post-treatment. In conclusion, the results from these experiments do not support a delayed or persistent alteration in cholinergic function after exposure to low doses of PB and/or sarin.

Acetylcholine↗