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Ying Liu

Publications and source records attributed to Ying Liu.

At least 37 records · Page 2Linked to original sources
PubMed2025

Transcriptional activation of regenerative hematopoiesis via microenvironmental sensing.

Transition between activation and quiescence states in hematopoietic stem and progenitor cells (HSPCs) is tightly governed by cell-intrinsic means and microenvironmental co-adaptation. Although this balance is fundamental for lifelong hematopoiesis and immunity, the underlying molecular mechanisms remain poorly defined. Multimodal analysis divulging differential transcriptional activity between distinct HSPC states indicates the presence of Fli-1 transcription factor binding motif in activated hematopoietic stem cells. We reveal that Fli-1 activity is essential during regenerative hematopoiesis in mice. Fli-1 directs activation programs while priming cellular sensory and output machineries, enabling HSPCs co-adoptability with a stimulated vascular niche through propagation of niche-derived angiocrine Notch1 signaling. Constitutively induced Notch1 signaling is sufficient to recuperate functional hematopoietic stem cells impairments in the absence of Fli-1, without leukemic transformation. Applying FLI-1 transient modified-mRNA transduction into latent adult human mobilized HSPCs, enables their niche-mediated expansion and superior engraftment capacities. Thus, decryption of stem cell activation programs offers valuable insights for immunological regenerative medicine.

Animals↗
PubMed2025

Proteomic Analysis of 442 Clinical Plasma Samples From Individuals With Symptom Records Revealed Subtypes of Convalescent Patients Who Had COVID-19.

After the coronavirus disease 2019 (COVID-19) pandemic, the postacute effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have gradually attracted attention. To precisely evaluate the health status of convalescent patients with COVID-19, we analyzed symptom and proteome data of 442 plasma samples from healthy controls, hospitalized patients, and convalescent patients 6 or 12 months after SARS-CoV-2 infection. Symptoms analysis revealed distinct relationships in convalescent patients. Results of plasma protein expression levels showed that C1QA, C1QB, C2, CFH, CFHR1, and F10, which regulate the complement system and coagulation, remained highly expressed even at the 12-month follow-up compared with their levels in healthy individuals. By combining symptom and proteome data, 442 plasma samples were categorized into three subtypes: S1 (metabolism-healthy), S2 (COVID-19 retention), and S3 (long COVID). We speculated that convalescent patients reporting hair loss could have a better health status than those experiencing headaches and dyspnea. Compared to other convalescent patients, those reporting sleep disorders, appetite decrease, and muscle weakness may need more attention because they were classified into the S2 subtype, which had the most samples from hospitalized patients with COVID-19. Subtyping convalescent patients with COVID-19 may enable personalized treatments tailored to individual needs. This study provides valuable plasma proteomic datasets for further studies associated with long COVID.

Humans↗
PubMed2025

Global Evolution and Transmission Dynamics of Enterovirus D68.

Enterovirus D68 (EV-D68), a serotype of the enterovirus species D, has garnered significant attention due to outbreaks reported in 2014, 2016, and 2018. In this study, 36 Chinese EV-D68 strains were isolated, sequenced, and combined with all EV-D68 VP1 sequences from GenBank to form a data set of 1679 sequences. This data set served as the basis for phylogenetic, evolutionary dynamics, phylogeographic, and key amino acid site mutation analyses of EV-D68. Based on the VP1 region, EV-D68 is classified into four genotypes (A-D), and seven subgenotypes (B1-B3, D1-D4), with B3 and D3 being the predominant subgenotypes. Bayesian skyline plots indicated that genotypes B and D experienced multiple population expansions, aligning with reported EV-D68 outbreaks. Phylogeographic analyses of the B3 subgenotypes revealed sequences from Europe and North America clustering into a single evolutionary branch, suggesting significant transmission between these regions. Additionally, mutation analysis identified VP1-98 as a high-frequency mutation site, differing significantly between the previously prevalent A and C genotypes and the currently prevalent B and D genotypes. However, the functional implications of this mutation require further investigation. This study provides a solid theoretical basis for epidemiological research, disease surveillance, and prevention efforts related to EV-D68.

Enterovirus Infections↗
PubMed2025

Frequent Genomic Recombination in the 5'-Proximal Region Characterizes Human Adenovirus Species C Evolution.

To advance our understanding of the molecular recombination dynamics of circulating human adenovirus species C (HAdV-C) strains, whole genome sequence (WGS) analysis of seven strains representing five genotypes (P1H1F1, P1H2F2, P89H5F5, P2H2F2, and Px1/Ps3H1F1) isolated from pediatric severe acute respiratory infection (SARI) cases in China were performed, involving sequence similarity assessment, phylogenetic inference, and recombination mapping. The genomic analysis of seven strains showed substantial nucleotide identity (93.5%-99.2%) and distinct recombination patterns. Further comparative recombinant analysis with eight prototype strains and 214 publicly available strains revealed that strains with high genomic similarity or evolutionary relatedness showed substantial conservation in the posterior genomic regions, while the 5'-proximal ~14 000 bp region, particularly E1 and E2B regulatory and replication-associated genes, displayed significant recombination activity. In addition, identical or similar recombination patterns were found in the genomes of strains with high sequence identity and homology, which had been detected by different surveillance systems, and in multiple provinces in China and other countries. Further analysis revealed an independent evolutionary cluster for two strains (Henan2018-431 and Jilin2019-101), which also harbored fragments of unknown origin within the E3 region, potentially representing novel HAdV-C variants. These findings highlight the critical role of frequent recombination in HAdV-C evolution, particularly in low-diversity genomic regions, and emphasize the importance of WGS-based surveillance for tracking emerging recombinant strains with public health implications.

Humans↗
PubMed2024

Oncogene-induced matrix reorganization controls CD8+ T cell function in the soft-tissue sarcoma microenvironment.

CD8+ T cell dysfunction impedes antitumor immunity in solid cancers, but the underlying mechanisms are diverse and poorly understood. Extracellular matrix (ECM) composition has been linked to impaired T cell migration and enhanced tumor progression; however, impacts of individual ECM molecules on T cell function in the tumor microenvironment (TME) are only beginning to be elucidated. Upstream regulators of aberrant ECM deposition and organization in solid tumors are equally ill-defined. Therefore, we investigated how ECM composition modulates CD8+ T cell function in undifferentiated pleomorphic sarcoma (UPS), an immunologically active desmoplastic tumor. Using an autochthonous murine model of UPS and data from multiple human patient cohorts, we discovered a multifaceted mechanism wherein the transcriptional coactivator YAP1 promotes collagen VI (COLVI) deposition in the UPS TME. In turn, COLVI induces CD8+ T cell dysfunction and immune evasion by remodeling fibrillar collagen and inhibiting T cell autophagic flux. Unexpectedly, collagen I (COLI) opposed COLVI in this setting, promoting CD8+ T cell function and acting as a tumor suppressor. Thus, CD8+ T cell responses in sarcoma depend on oncogene-mediated ECM composition and remodeling.

CD8-Positive T-Lymphocytes↗
PubMed2007

Regulation of SOCS-3 expression by leptin and its co-localization with insulin receptor in rat skeletal muscle cells.

Obesity is a well-defined risk factor for the development of insulin resistance in target tissues, such as skeletal muscle, and thus type 2 diabetes. This may occur due to endocrine effects mediated by adipokines including leptin, the product of the obese (ob) gene, whose circulating levels positively correlate with body mass index. Induction of suppressor of cytokine-3 (SOCS-3) protein expression has been implicated as a possible mechanism of leptin-induced insulin resistance. Here, we show that treatment of rat skeletal muscle cells with leptin activated the SOCS-3 gene promoter and caused a time-dependent increase in both SOCS-3 mRNA and protein content. Confocal microscopy demonstrated increased co-localization of SOCS-3 with insulin receptor in leptin-treated cells and we confirmed a direct interaction between these two proteins by showing increased coimmunoprecipitation of SOCS-3 and insulin receptor after exposure of cells to leptin. However, the expected functional consequences were not observed, as we saw no change in basal or insulin-stimulated glucose uptake and phosphorylation of GSK3beta, Akt (T308 and S473) or ERK1/2. In summary, leptin induced SOCS-3 expression and its association with the insulin receptor in rat skeletal muscle cells but functional significance of this increase was not apparent upon measuring glucose uptake.

Animals↗
PubMed2007

Single nucleotide polymorphisms in the proximal promoter region of apolipoprotein M gene (apoM) confer the susceptibility to development of type 2 diabetes in Han Chinese.

OBJECTIVE: Dyslipidemia correlating to insulin resistance is one of the key features in type 2 diabetes (T2D). Recent studies have demonstrated that apolipoprotein M (apoM) is important for the formation of prebeta-high-density lipoprotein (HDL) and cholesterol (CHO) efflux in macrophages to HDL. In the present study, we investigated the potential association of apoM genetic variation with the development of T2D. METHODS: Single nucleotide polymorphisms (SNPs) C-1065A, T-855C and T-778C in the proximal promoter region of apoM gene were validated to represent in Han Chinese. Further genotyping experiments in 170 T2D patients and 156 non-diabetic control subjects were performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Single marker analysis for SNP T-778C indicated that T2D patients had increased frequency of C allele in comparison with non-diabetic controls (10.6% versus 5.8%, P = 0.026, OR = 1.934). In non-diabetic controls, the carriers with CT and CC genotypes had higher plasma CHO (221.7 versus 204.2 mg/dL, P = 0.033) and fasting plasma glucose (FPG) (92.6 versus 89.7 mg/dL, P = 0.041) levels than the subjects with TT genotype. Further analysis with adjustment for age, BMI, SBP, DBP, CHO and TG demonstrated that this SNP was strongly associated with T2D (P = 0.013, OR = 2.287). Haplotype analysis for those three SNPs, however, indicated that the common haplotypes were less informative than studying the role of the T-778C variant independently of the haplotype context. CONCLUSION: The present study provided the first evidence that SNP T-778C in the proximal promoter region of apoM gene was associated with the levels of plasma CHO and FPG and also conferred the risk in the development of T2D among Han Chinese.

Aged↗
PubMed2007

Expression of insulin-like growth factors systems in cloned cattle dead within hours after birth.

Cloning by somatic nuclear transfer is an inefficient process in which many of the cloned animals die shortly after birth and display organ abnormalities. In an effort to determine the possible roles IGFs played in neonatal death and organ abnormalities, we have examined expression patterns of eight genes in insulin-like growth factor (IGF) systems (IGF1, IGF2, IGF1R, IGF2R, IGFBP-1, IGFBP-2, IGFBP-3, and IGFBP-4) in six organs (heart, liver, spleen, lung, kidney, and brain) of both neonatal death cloned bovines (n = 9) and normal control calves (n = 3) produced by artificial insemination (AI) using real-time quantitative RT-PCR. The effect of the age of the fibroblast donor cell on the gene expression profiles was also investigated. Aberrant expressions of six genes (IGF2, IGF1R, IGF2R, IGFBP-2, IGFBP-3, and IGFBP-4) were found in some studied tissues, but the expression of two genes (IGF1 and IGFBP-1) had similar levels with the normal controls. For the studied genes, kidney was the organ that was most affected (five genes) by gene downregulation, whereas spleen was the organ that was not affected. The two upregulation genes were in brain, but both of downregulation and upregulation were found in the heart, liver, and lung. The expression of three genes (IGF2R, IGFBP-4, and IGF2) in some tissues showed significant differences between AF cell-derived and FF cell-derived clones. Our results suggest that aberrations in gene expression within IGF systems were found in most cloned bovine tissues of neonatal death. Because IGF systems play an important role in embryo development and organogenesis, the aberrant transcription patterns detected in these clones may contribute to the defects of organs reported in neonatal death of clones.

Abnormalities, Multiple↗
PubMed2006

High frequency deep brain stimulation: what are the therapeutic mechanisms?

High frequency deep brain stimulation (HFS) used to treat the symptoms of Parkinson's disease (PD) was first assumed to act by reducing an excessive tonic GABAergic inhibitory output from the internal globus pallidus (GPi). Stimulation in GPi might produce this directly by mechanisms such as depolarization block or activation of presynaptic inhibitory fibers, and the same mechanisms evoked by HFS in the subthalamic nucleus (STN) could reduce the excitatory action of STN on GPi neurons. Although somatic recordings from neurons near the stimulation site may appear to support this potential mechanism, the action downstream from the site of stimulation often is not consistent with this interpretation. A more parsimonious explanation for the similar effects of HFS in STN or GPi and a lesion of either of these structures is that both HFS and pallidotomy interrupt an abnormal pattern of firing in cortico-basal ganglia-thalamocortical loops that is responsible for the symptoms of PD.

Cerebrovascular Circulation↗
PubMed2006

A genotype-independent real-time PCR assay for quantification of hepatitis B virus DNA.

Accurate quantification of hepatitis B virus (HBV) DNA levels is important for monitoring patients with chronic HBV infection and for assessing their responses to antiviral therapy. This study aimed to develop a real-time PCR assay that is sensitive and can accurately quantify a wide range of HBV DNA levels across the known HBV genotypes. An "in-house" real-time PCR assay using primers and a TaqMan probe in a highly conserved region of the HBV surface gene was designed. The assay was standardized against a WHO standard and validated against plasmids of HBV genotypes A through H. The linear quantification range was approximately 5 x 10(0) to 2.0 x 10(9) IU/ml. Results of samples from patients infected with HBV genotypes A through H tested using our real-time "in-house" PCR assay showed an excellent correlation with those of the Cobas Amplicor HBV Monitor (R2=0.9435) and the Cobas TaqMan HBV (R2=0.9873) tests. We have established a real-time PCR assay that is genotype independent and can accurately quantify a wide range of HBV DNA levels. Further studies of additional samples are ongoing to validate the genotype independence of our assay.

DNA Primers↗
PubMed2006

The role of ROS in microcystin-LR-induced hepatocyte apoptosis and liver injury in mice.

Microcystin-LR (MC-LR) produced by cyanobacteria in diverse water systems is a potent specific hepatotoxin and has been documented to induce hepatocyte apoptosis and liver injury; however, the mechanisms have not been fully elucidated. In the present study, we investigated whether MC-LR stimulated ROS generation in the liver of mice and the role of ROS in the pathogenesis of MC-LR-induced liver injury in vivo. MC-LR treatment (60 microg/kg of body weight) for 12h prompted large amount of ROS generation in mice liver, upregulated the expression of Bax and Bid, caused the mitochondrial membrane potential (MMP) loss and hepatocyte apoptosis as well as liver injury. While pretreatment with antioxidants, oral administration of vitamin C (250mg/kg of body weight, dissolved in double distill water) and vitamin E (200mg/kg of body weight, dissolved in corn oil) per day for 3 days continually, significantly reduced the generation of ROS and effectively inhibited the MC-LR-induced hepatocyte apoptosis and liver injury, suggesting that ROS played a critical role in MC-LR-induced hepatocyte apoptosis and liver injury. The protective effect of vitamin C and E also suggested the potential interest in the clinical treatment of MC-LR-induced liver injury and hepatotoxicity.

Alanine Transaminase↗
PubMed2006

p21(Waf1/Cip1) deficiency stimulates centriole overduplication.

Inactivation of the cyclin-dependent kinase (CDK) inhibitor p21(Waf1/Cip1) (CDKN1; hereafter p21) has previously been implicated in the induction of numerical centrosome alterations. It is unclear, however, whether p21 deficiency deregulates the centrosome duplication cycle itself or causes an accumulation of centrosomes due to cell division failure and/or polyploidization. Using a novel marker for maternal centrioles, Cep170, we show here that knock-down of p21 protein expression in murine myeloblasts can stimulate excessive centriole numbers in the presence of only one mature centriole. These results indicate that p21 deficiency can trigger a bona fide overduplication of centrioles and that aberrant centrosome numbers cannot solely be explained by polyploidization as suggested by previous studies. Our findings underscore that impaired p21 expression may function as a driving force for chromosomal instability and highlight the importance of markers for maternal centrioles such as Cep170 to elucidate the pathogenesis of numerical centriole aberrations in tumor cells.

Animals↗
PubMed2006

Genome-wide atlas of gene expression in the adult mouse brain.

Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.

Animals↗
PubMed2006

Sequential priming and boosting with heterologous HIV immunogens predominantly stimulated T cell immunity against conserved epitopes.

BACKGROUND: The effort to develop an effective preventive vaccine against HIV-1 infection is challenged by the wide genetic diversity of HIV-1 among different isolates. OBJECTIVES: To explore a new vaccination strategy by using heterologous HIV immunogens derived from different clades for sequential priming and boosting. METHODS: HIV Env and Gag immunogens derived from Thailand B (B'), C/B' recombinant and A/E recombinant were selected as these three clades account for 29%, 45% and 15% of HIV-1 prevalence in China, respectively. Three humanized fusion genes of env and gag derived from those three clades were synthesized and inserted into DNA and recombinant Tiantan vaccinia vectors as model vaccines. C57BL/6 and Balb/c mice were used as animal model. Peptides spanning the entire Env and Gag were used as stimuli and Elispot assay was used to assess the T cell immunity. RESULTS: Sequential priming and boosting was observed with heterologous HIV immunogens predominantly stimulated T cell immunity against conserved epitopes, whereas a single vaccine derived from one clade or the mixture of multiple vaccines from different clades primarily raised T cells against less conservative or non-conservative epitopes. CONCLUSIONS: This is the first demonstration of a practical strategy to raise immune responses against conserved epitopes. This strategy has important implications for vaccine development against HIV and other pathogens that have high genetic diversity, such as influenza.

AIDS Vaccines↗
PubMed2006

Effect of nicotine on in vitro maturation of bovine oocytes.

The putative effect of nicotine on maturation and the chromosomal complement of bovine oocytes were investigated in the present study. Cumulus-enclosed oocytes were incubated in maturation medium with 0, 0.5, 1.0, 2.5, 5.0, and 10.0 mmol concentrations of nicotine. The results indicated that: (1) nicotine affected cumulus cell expansion in a dose-dependent manner and the perivitelline space failed to form when concentrations were equal to or greater than 5.0 mmol; (2) oocytes treated with 0.5 and 1.0 mmol nicotine concentrations resulted in maturation rates (83.3% and 85.9%, respectively) which was similar to the control (86.2%), whereas treatment with 2.5 and 5.0 mmol concentrations significantly decreased maturation rates to 70.2% and 26.7%, respectively; (3) nicotine at or over 2.5 mmol caused extremely irregular meiotic spindles and interrupted microfilament organization; (4) chromosomal analyses of oocytes with PB1 showed that oocytes derived from 0.5 and 1.0 mmol nicotine groups had haploid complements similar to the control (87-90%), but when the concentrations were increased to 2.5 and 5.0 mmol the haploid state was significantly reduced to around 70%; (5) oocytes at GVBD (germinal vesicle breakdown) and metaphase I stages were less affected by nicotine at 5.0 and 10.0 mmol concentrations than GV-stage oocytes; (6) maturation rates of the short-term nicotine-treated oocytes could be improved when subsequently incubated in normal maturation medium. Prolonged culture of nicotine-pretreated oocytes resulted in self-activation and some oocytes formed 1 or 2 pronuclei. In conclusion, nicotine affects bovine oocyte cumulus cell expansion, maturation rate, and chromosomal complement in a dose-dependent and an oocyte-stage-dependent manner.

Animals↗
PubMed2006

Development of a highly enantioselective capacitive immunosensor for the detection of alpha-amino acids.

This work describes a highly enantioselective and sensitive immunosensor for the detection of chiral amino acids based on capacitive measurement. The sensor was prepared by first binding mercaptoacetic acid to the surface of a gold electrode, followed by modification with tyramine utilizing carbodiimide activation. The hapten 4-amino-D-phenylalanine was then covalently immobilized onto the electrode by diazotization. Stereoselective binding of an anti-D-amino acid antibody to the hapten-modified sensor surface resulted in capacitance changes that were detected with high sensitivity by a potentiostatic step method. Using capacitance measurement, detection limits of 5 pg of antibody/mL were attained. The exquisite stereoselectivity of the antibody was also utilized in a competitive setup to quantitatively determine the concentration of the analyte d-phenylalanine in nonracemic samples containing both enantiomers of this amino acid. Trace impurities of d-phenylalanine as low as 0.001% could be detected.

Amino Acids↗
PubMed2006

Cross-species transcriptional profiles establish a functional portrait of embryonic stem cells.

An understanding of the regulatory mechanisms responsible for pluripotency in embryonic stem cells (ESCs) is critical for realizing their potential in medicine and science. Significant similarities exist among ESCs harvested from different species, yet major differences have also been observed. Here, by cross-species analysis of a large set of functional categories and all transcription factors and growth factors, we reveal conserved and divergent functional landscapes underlining fundamental and species-specific mechanisms that regulate ESC development. Global transcriptional trends derived from all expressed genes, instead of differentially expressed genes alone, were examined, allowing for a higher discriminating power in the functional portrait. We demonstrate that cross-species correlation of transcriptional changes that occur upon ESC differentiation is a powerful predictor of ESC-important biological pathways and functional cores within a pathway. Hundreds of functional modules, as defined by Gene Ontology, were associated with conserved expression patterns but bear no overt relationship to ESC development, suggestive of new mechanisms critical to ESC pluripotency. Yet other functional modules were not conserved; instead, they were significantly up-regulated in ESCs of either species, suggestive of species-specific regulation. The comparisons of ESCs across species and between human ESCs and embryonal carcinoma stem cells suggest that while pluripotency as an essential function in multicellular organisms is conserved throughout evolution, mechanisms primed for differentiation are less conserved and contribute substantially to the differences among stem cells derived from different tissues or species. Our findings establish a basis for defining the "stemness" properties of ESCs from the perspective of functional conservation and variation. The data and analyses resulting from this study provide a framework for new hypotheses and research directions and a public resource for functional genomics of ESCs.

Animals↗