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Biomedical subjects

Yu Feng

Publications and source records attributed to Yu Feng.

At least 19 recordsLinked to original sources

Air contamination and cross-room transmission of carbapenem resistant Acinetobacter baumannii in ICU.

Air contamination of carbapenem-resistant Acinetobacter baumannii (CRAB) was investigated in an ICU with genome sequencing. CRAB was recovered from air samples (n=13) and patients (n=9) and belonged to ST2 (n=16) or ST164 (n=6). Four of the 9 ST2 clones were associated with transmission through the air within rooms or cross-room. All ST164 isolates belonged to a common clone and were found in two rooms. CRAB air dispersal may cause cross-room transmission at a long distance.

Acinetobacter baumannii↗

Single-cell multi-omics dissects transcript isoform and immune repertoire dynamics in human immunosenescence.

Immunosenescence, a major hallmark of systemic aging, refers to the progressive functional decline of the immune system. This decline not only compromises host defense and immunological memory but also fuels chronic inflammation and tissue degeneration (collectively known as inflammaging). While single-cell RNA sequencing (scRNA-seq) has revealed transcriptomic alterations associated with immune aging, analyses restricted to transcript abundance fail to capture deeper regulatory layers, such as transcript isoform diversity and the remodeling of immune receptor repertoires. To address this limitation, we present a human peripheral immune single-cell multi-omics atlas that integrates gene expression, transcript isoform diversity, and immune receptor repertoires. By combining single-cell full-length transcriptome sequencing (scCycloneSEQ), short-read scRNA-seq, and single-cell immune receptor sequencing (scTCR/BCR-seq), we systematically profiled peripheral blood mononuclear cells (PBMCs) from healthy donors aged 30-40 and 60-70 years. Our analyses uncovered extensive age-related remodeling of immune cell composition, functional states, and TCR/BCR diversity. Notably, we found that CD4+ effector memory T cells exhibited widespread differential isoform usage (DIU), 3'UTR length variation, and a marked reshaping of cytotoxic T lymphocyte (CTL) clonotypes-all of which were closely associated with aging-related inflammation and cellular senescence. This multi-omics atlas delineates key molecular features of immunosenescence and provides a high-resolution resource for deciphering the regulatory architecture underlying immune aging.

TCR/BCR↗

Full-length single-cell spatial transcriptomics reveals spatial and cell-type-specific transcript isoforms in the primate brain.

The primate brain exhibits complex RNA alternative splicing heterogeneity crucial for functional complexity, yet systematic spatial isoform characterization has been lacking. We developed Fullscope-seq, a full-length single-molecule large field-of-view spatial transcriptomics sequencing method at single-cell resolution, based on programmed concatenation cDNA for multiple long-read sequencing platforms. Applying Fullscope-seq to the macaque brain, we uncovered thousands of genes exhibiting differential transcript usage (DTU) across cortical layers, cell types and brain regions. Fullscope-seq resolved hundreds of major isoform switches across distinct brain regions and identified DTUs between superficial and deep cortical layers. Cortical layer-specific DTUs showed cell-composition dependence, whereas regional DTUs were regulated according to both cellular composition and spatial contexts. These isoform variations showed substantial enrichment for neuropsychiatric disorder-associated genes and were conserved across platforms and species. Our study establishes a scalable framework for spatial isoform analysis and provides a resource for understanding transcriptomic diversity in complex tissues.

Animals↗

Enhanced invasiveness promotes the dominance of a widely-distributed carbapenem-resistant virulence-plasmid-carrying Klebsiella pneumoniae sublineage.

Carbapenem-resistant Klebsiella pneumoniae (CRKP), a WHO's critical priority pathogen, continuously evolves to generate health-threatening high-risk (sub)lineages. Here, we conducted a 10-year surveillance of nosocomial CRKP infections, collecting and whole-genome sequencing 1513 clinical isolates, accompanied by clinical data. We applied fine-scale genome analysis for 60,724 non-local public-available K. pneumoniae genomes. We identified a predominant ST11-KL64 sublineage widely-disseminated across China and internationally-distributed. Isolates of this sublineage were more frequently recovered during seasonal influenza peaks and harbored plasmids encoding 'hypervirulence' factors but caused no increase in patient mortality. Instead, they exhibited enhanced invasiveness and translocation capacity. Mechanistically, this suggested highly invasive CRKP (hiCRKP) sublineage showed elevated resistance to macrophage-mediated phagocytosis, partly due to the virulence-encoding plasmid and the loss of two chromosomal fimD gene copies. Additionally, hiCRKP isolates carried more antimicrobial resistance genes, resulting in enhanced resistance to clinically important quinolones and tetracyclines. To address the hiCRKP-imposed challenge, we constituted a phage cocktail, which significantly improved survival in a murine infection model. Our findings unveil a clinically-relevant high-risk sublineage resulted from the ongoing evolutionary diversification of CRKP. Importantly, the 'hypervirulent' CRKP is more potent to cause diseases rather than the thought-to-be more deaths, explaining its rapid emergence in healthcare settings.

Klebsiella pneumoniae↗

Comprehensive genomic and computational insights into Brucella suis: pan-genome analysis, evolutionary perspectives, and in-silico vaccine design.

BACKGROUND: Brucella suis is a zoonotic intracellular pathogen responsible for brucellosis, mainly in swine and humans. Although numerous genome sequences are publicly available, an integrative genomic analysis combining pan-genome architecture, structural organization, evolutionary relationships, and vaccine-associated targets remains limited. RESULTS: In this study, we analyzed 91 publicly available B.suis genomes to characterize their pan-genome composition and genomic structure. The pan-genome exhibited an open configuration, indicating continued genomic diversification. A total of 2,146 core genes were identified, representing conserved functions essential for species maintenance, while the accessory genome reflected strain-level variability. Phylogenetic reconstruction based on single-copy orthologs revealed distinct evolutionary clades among the strains. A complementary phylogenetic analysis of pan-genome gene presence-absence patterns further supported clade differentiation and highlighted variation in accessory gene repertoires. Comparative synteny and genome structural analyses demonstrated largely conserved chromosomal organization with localized rearrangements across strains. Screening of the core proteome identified 64 putative antigenic proteins with predicted surface localization and immunogenic properties. Additionally, resistance-associated determinants related to tetracycline and doxycycline were detected in one genome within the dataset. CONCLUSIONS: This comprehensive genomic analysis defines the pan-genome structure, evolutionary relationships, and genome organization of B.suis. The integration of core and pan-genome-based phylogenies provides complementary insights into strain diversification, while the identified conserved antigenic candidates offer a foundation for future experimental validation and rational vaccine development strategies.

Genome, Bacterial↗

Evolutionary legacy of the "living fossil" genus Parrotia (Hamamelidaceae): genomic insights into species divergence and polygenic adaptation.

Despite their long evolutionary history, the genomic basis of adaptation and speciation in "living fossil" plants remain largely unexplored. Parrotia, a Tertiary relict tree genus with two extant species, P. subaequalis and P. persica, exhibits a disjunct distribution between East Asia and West Asia. Here, we present the first chromosome-level assemblies for both species, confirmed their sibling relationship, and dated the speciation event to the early Miocene. The recent proliferation of long-terminal repeat retrotransposons has driven the genome expansion in P. subaequalis. We detected widespread heterogeneous genomic differentiation between species. Extensive signals of divergent selection, local adaptation, and elevated Ka/Ks ratios in Parrotia indicate that this genus has undergone adaptive evolution in distinct refugia, challenging the notion of it as an "evolutionary dead end". Our findings provide new insights into the genomic evolution, environmental adaptation, and speciation of this "living fossil" tree genus.

Genome, Plant↗

The serotonin receptor HTR1B: gene polymorphisms in attention deficit hyperactivity disorder.

Serotonin plays an essential role in cognition, locomotor activity, and the regulation of sleep, pain, mood, and aggression. Polymorphisms of the HTR1B gene have been implicated in a variety of psychiatric disorders including attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The objectives of this study were to: (i) expand our original investigation of the relationship between the HTR1B receptor gene and attention deficit/hyperactivity and; (ii) to investigate a possible association of obsessive behaviors/perfectionism and the HTR1B gene in a sample of 203 families with an ADHD proband. Six single nucleotide polymorphisms (SNPs) of the HTR1B receptor gene were genotyped using standard methods. Evidence for an association between the HTR1B gene and ADHD as a qualitative diagnosis, or the inattentive and hyperactive-impulsive quantitative traits was not supported by either TDT single marker analysis or haplotype analysis. In addition we did not find evidence to suggest an association between HTR1B and perfectionism in this sample of ADHD families.

Adolescent↗

Inhibitor discovery targeting the intermediate structure of beta-amyloid peptide on the conformational transition pathway: implications in the aggregation mechanism of beta-amyloid peptide.

Abeta peptides cleaved from the amyloid precursor protein are the main components of senile plaques in Alzheimer's disease. Abeta peptides adopt a conformation mixture of random coil, beta-sheet, and alpha-helix in solution, which makes it difficult to design inhibitors based on the 3D structures of Abeta peptides. By targeting the C-terminal beta-sheet region of an Abeta intermediate structure extracted from molecular dynamics simulations of Abeta conformational transition, a new inhibitor that abolishes Abeta fibrillation was discovered using virtual screening in conjunction with thioflavin T fluorescence assay and atomic force microscopy determination. Circular dichroism spectroscopy demonstrated that the binding of the inhibitor increased the beta-sheet content of Abeta peptides either by stabilizing the C-terminal beta-sheet conformation or by inducing the intermolecular beta-sheet formation. It was proposed that the inhibitor prevented fibrillation by blocking interstrand hydrogen bond formation of the pleated beta-sheet structure commonly found in amyloid fibrils. The study not only provided a strategy for inhibitor design based on the flexible structures of amyloid peptides but also revealed some clues to understanding the molecular events involved in Abeta aggregation.

Amyloid↗

Pharmacokinetics of CPU0213, a novel endothelin receptor antagonist, after intravenous administration in mice.

AIM: To determine the pharmacokinetics associated with acute toxic doses of CPU0213, a novel endothelin receptor antagonist in mice after a single intravenous administration. METHODS: Concentrations in serum and the pharmacokinetic parameters of CPU0213 were assayed by high pressure liquid chromatography (HPLC) following a single intravenous bolus of CPU0213 at concentrations of 25, 50, and 100 mg/kg in mice. The intravenous acute toxicity of CPU0213 was also assessed in mice. RESULTS: A simple, sensitive and selective HPLC method was developed for quantitative determination of CPU0213 in mouse serum. The concentration-time data conform to a 2-compartment model after iv administration of CPU0213 at concentrations of 25, 50, 100 mg/kg. The corresponding distribution half-lives (T1/2 alpha ) were 3.6, 4.2, 1.1 min and the elimination half-lives (T1/2beta) were 39.4, 70.3, 61.9 min. There was a linear increase in C0 proportional to dose, and the same as AUC(0-t) and AUC(0-infinity);. AUC(0-t) and AUC(0-infinity) were 4.511, 13.070, 23.666 g x min x L(-1 ) and 4.596, 13.679, 24.115 g x min x L(-1), respectively. The intravenous LD50 was 315.5 mg/kg. CONCLUSION: First order rate pharmacokinetics were observed for CPU0213 within the range of doses used, and the acute toxicity of CPU0213 is mild.

Animals↗

[Effect of erythromycin on apoptosis of epithelial cell in nasal polyps].

OBJECTIVE: To study the effect of erythromycin on apoptosis and expression of Bax and Bcl-2 of epithelial cell in nasal polyps. METHODS: Epithelial cells from thirty nasal polyps and fifteen inferior turbinates were cultured in Dulbecco Eagle and Ham F12 (1:1) and divided into two groups (one group were treated with Erythromycin). Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling and expression of Bcl-2 and Bax detected by immunohistochemistry at 1, 3, 5 days after culture. RESULTS: The apoptosis indexes (AI) of epithelial cell in nasal polyps after cultured for 1, 3, 5 days with erythromycin were (33.23 +/- 6.50)%, (38.21 +/- 7.22)% and (52.63 +/- 7.86)% respectively. The AI of epithelial cell in inferior turbinates were (31.02 +/- 5.60)%, (32.13 +/- 7.15)% and (39.64 +/- 7.48)% respectively. There was significant difference between two groups at 5 day after culture (P < 0.05). Expression of Bax and Bcl-2 of epithelial cell was significantly higher in nasal polyps than that in inferior turbinates (P < 0.01). Expression of Bax of epithelial cell cultured with erythromycin was significantly higher than that in the controls (P < 0.05). Apoptosis was clearly promoted after 5 day culture with Erythromycin (P < 0.05). CONCLUSIONS: Erythromycin promoted expression of Bax and apoptosis of epithelial cell in nasal polyps.

Adolescent↗

Sequence variation in the 3'-untranslated region of the dopamine transporter gene and attention-deficit hyperactivity disorder (ADHD).

The dopamine transporter gene (DAT1) has been reported to be associated with attention-deficit hyperactivity disorder (ADHD) in a number of studies [Cook et al. (1995): Am J Human Genet 56(4):9993-998; Gill et al. (1997): Mol Psychiatry 2(4):311-313; Waldman et al. (1998): Am J Human Genet 63(6):1767-1776; Barr et al. (2001): Biol Psychiatry 49(4):333-339; Curran et al. (2001): Mol Psychiatry 6(4):425-428; Chen et al. (2003): Mol Psychiatry 8(4):393-396]. Specifically, the 10-repeat allele of the 40-bp variable number of tandem repeats (VNTR) polymorphism located in the 3' untranslated region (UTR) of the gene has been found to be associated with ADHD. There is evidence from in vitro studies indicating that variability in the repeat number, and sequence variation in the 3'-UTR of the DAT1 gene may influence the level of the dopamine transporter protein [Fuke et al. (2001): Pharmacogenomics J 1(2):152-156; Miller and Madras (2002): Mol Psychiatry 7(1):44-55]. In this study, we investigated whether DNA variation in the DAT1 3'UTR contributed to ADHD by genotyping DNA variants around the VNTR region in a sample of 178 ADHD families. These included a MspI polymorphism (rs27072), a DraI DNA change (T/C) reported to influence DAT1 expression levels, and a BstUI polymorphism (rs3863145) in addition to the VNTR. We also screened the VNTR region by direct resequencing to determine if there was sequence variation within the repeat units that could account for the association. Our results indicate that DAT1 is associated with ADHD in our sample but not with alleles of the VNTR polymorphism. We did not find any variation in the sequence for either the 10- or 9-repeat alleles in the probands screened nor did we observe the reported DraI (T/C) variation. Our results therefore refute the possibility of the reported DraI variation or alleles of the VNTR as the functional variants contributing to the disorder.

3' Untranslated Regions↗

Photon-driven nanomechanical cyclic motion.

Microcantilevers modified by a monolayer of azobenzene molecules bend up and down periodically, switched by a 365 nm UV light, as a result of the conversion of the two configurations of azobenzene molecules in the monolayer.

Journal Article↗

A vaccinia replication system for producing recombinant hepatitis C virus.

AIM: To develop a cell culture system capable of producing high titer hepatitis C virus (HCV) stocks with recombinant vaccinia viruses as helpers. METHODS: Two plasmids were used for the generation of recombinant HCV: one containing the full-length HCV cDNA cloned between T7 promoter and T7 terminator of pOCUS-T7 vector, and the other containing the HCV polyprotein open reading frame (ORF) directly linked to a vaccinia late promoter in PSC59. These two plasmids were co-transfected into BHK21 cells, which were then infected with vTF7-3 recombinant vaccinia helper viruses. RESULTS: After 5 d of incubation, approximately 3.6X10(7) copies of HCV RNA were present per milliliter of cell culture supernatant, as detected by fluorescence quantitative RT-PCR (FQ-PCR). The yield of recombinant HCV using this cell system increased 100- to 1 000- fold compared to in vitro- transcribed HCV genomic RNA or selective subgenomic HCV RNA molecule method. CONCLUSION: This cell culture system is capable of producing high titer recombinant HCV.

Animals↗

[Determination of fatty acid methyl ester ethoxylates by gas chromatography].

A gas chromatographic (GC) method for the determination of fatty acid methyl ester ethoxylates (FMEO) is described. After hydrolyzed in 0.5 mol/L KOH ethanol solution, ester linkage in FMEO was broken into two parts, i.e., hydrophobic groups and hydrophilic groups, which made feasible for the further derivatization of both groups using appropriate derivatizing agents. Hydrophobic groups were esterified by sulfate acid-methanol mixture and hydrophilic groups were etherified by hexamethyldisilyamine and trimethylchlorosilane prior to GC determination. Quantitative results were obtained by the normalization of peak areas of the chromatograms. Compared with previous methods, this one is simple, quick and has a good reproducibility, especially for FMEOs with hydrophobic groups of mixed chain lengths.

Chromatography, Gas↗

Determination of trace europium by use of the new fluorescence system europium-sparfloxacin-1,10-phenanthroline-sodium dodecyl sulfate.

A new lanthanide-sensitized luminescence system: europium-sparfloxacin-1,10-phenanthroline-sodium dodecyl sulfate has been discovered. The spectrofluorimetric properties of the system were studied. The effect of experimental conditions on the fluorescence intensity was defined. Under the optimum conditions, the fluorescence intensity of the system is a linear function of the concentration of europium in the range 5.0 x 10(-9) - 1.0 x 10(-6) mol L(-1) and the detection limit is 1.0 x 10(-10) mol L(-1). The system was used for the determination of trace amounts of europium in rare earth samples with satisfactory results.

Journal Article↗