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Biomedical subjects

Yu He

Publications and source records attributed to Yu He.

At least 19 recordsLinked to original sources

Hyperlactate-Associated Lysine Lactylome Remodeling in Laryngeal Squamous Cell Carcinoma.

Laryngeal squamous cell carcinoma (LSCC) lacks reliable biomarkers, and the roles of lactate metabolism and lysine lactylation (Kla) remain largely unknown. We profiled the lysine lactylome of LSCC, paired it with adjacent normal tissues, and integrated the data with quantitative proteomic and transcriptomic analyses. LSCC exhibited a hyperlactate-associated phenotype characterized by dysregulated lactate-related genes (LRGs), altered protein abundance, increased tissue lactate, and globally increased Kla levels. Data-independent acquisition mass spectrometry (DIA-MS) identified 1616 Kla sites on 1468 peptides from 688 proteins, with most differential sites being upregulated in tumors. Differentially lactylated proteins were enriched in cell-matrix adhesion, cell migration, chromatin remodeling, and gene-regulatory processes and were clustered into cytoskeletal and nuclear regulatory modules. Multiple Kla sites were also detected on the core histones. Immunoblotting and tissue microarray analyses confirmed increased pan-Kla expression in the LSCC. Pan-Kla levels were independent of sex and age but positively correlated with the tumor stage and lymph-node metastasis. These findings provide a systematic resource for hyperlactate-associated lactylome remodeling in LSCCs and identify candidate Kla-related molecular features associated with clinicopathological progression for future functional and clinical evaluation.

Humans↗

Social isolation and 59 common health conditions: insights from observational and genetics analyses.

BACKGROUND: The impacts of social isolation on diverse health conditions and how it contributes to health risks remain unclear. We aimed to investigate the associations of social isolation with 59 health conditions among older adults. METHODS: Participants from the UK Biobank without baseline diagnosis of the included diseases were selected. Social isolation was assessed with three questions. The 59 health conditions included all-cause mortality, 5 cause-specific mortalities, and 53 diseases. We used an instrumental variable from multivariable common factor GWAS in Mendelian randomization (MR) to explore causal links of social isolation with diseases. Omics analyses were conducted to assess the roles of Olink plasma proteins and metabolomics, and PERM was calculated to evaluate the influence of other factors. RESULTS: A total of 489,741 individuals [266,706 (54.5%) women; mean age 56.5 years (SD 8.1)] were included. During a median follow-up of 12.5 years, social isolation was uncorrelated with the majority of 59 health conditions. Significantly, it was associated with increased risks of all-cause [adjusted HR (aHR) 1.28, 95% CI 1.25-1.32], 5 cause-specific mortalities (aHR range, 1.18-1.38), and 11 specific diseases (aHR range, 1.08-1.17). Living alone was the strongest item of isolation in predicting mortality (aHR range, 1.18-1.45) and selected diseases. MR analyses offered little evidence to support a causal link between social isolation and these diseases. The proteins involved in these associations are predominantly related to "response to stimulus". Proteomic signatures (PERM, 36%-49%), health behaviours (32%-59%), and socioeconomic factors (22%-42%) were the main explanatory factors linking social isolation to 8 health outcomes. CONCLUSIONS: Social isolation is associated with elevated risks of 17 out of the 59 examined adverse health outcomes, predominantly mortality-related conditions; however, MR analyses indicate an absence of evidence supporting causality for these associations.

Humans↗

Highly connected two-dimensional crystals of DNA six-point-stars.

This paper reports a novel DNA six-point-star motif assembled from only three different DNA single-strands. This motif readily assembles into hexagonal two-dimensional arrays with high connectivity. Such a high connectivity could potentially improve the array stability.

Crystallization↗

Geometric self-sorting in DNA self-assembly.

Two types of DNA star motifs (tiles) can recognize and associate with like tiles to form 2D arrays but exclude unlike tiles even though the local interactions between any two tiles are exactly the same.

Crystallization↗

Antibody nanoarrays with a pitch of approximately 20 nanometers.

We have developed a strategy for preparing antibody nanoarrays by DNA templating. In the resulting tetragonal antibody arrays, each spot is a similarly orientated, individual antibody molecule (IgG). The separation between two adjacent IgG molecules is only approximately 20 nm.

Antibodies↗

Changes in auditory cortex parallel rapid perceptual learning.

Learning perceptual skills is characterized by rapid improvements in performance within the first hour of training (fast perceptual learning) followed by more gradual improvements that take place over several daily practice sessions (slow perceptual learning). Although it is widely accepted that slow perceptual learning is accompanied by enhanced stimulus representation in sensory cortices, there is considerable controversy about the neural substrates underlying early and rapid improvements in learning perceptual skills. Here we measured event-related brain potentials while listeners were presented with 2 phonetically different vowels. Listeners' ability to identify both vowels improved gradually during the first hour of testing and was paralleled by enhancements in an early evoked response ( approximately 130 ms) localized in the right auditory cortex and a late evoked response ( approximately 340 ms) localized in the right anterior superior temporal gyrus and/or inferior prefrontal cortex. These neuroplastic changes depended on listeners' attention and were preserved only if practice was continued; familiarity with the task structure (procedural learning) was not sufficient. We propose that the early increases in cortical responsiveness reflect goal-directed changes in the tuning properties of auditory neurons involved in parsing concurrent speech signals. Importantly, the neuroplastic changes occurred rapidly, demonstrating the flexibility of human speech segregation mechanisms.

Acoustic Stimulation↗

[Assessment of the characteristics of echocardiography in pediatric patients with total anomalous pulmonary venous connection].

OBJECTIVE: To assess the accuracy of echocardiography in diagnosis of total anomalous pulmonary venous connection (TAPVC). METHODS: A combination of suprasternal, parasternal, subcostal and apical views were employed to diagnose TAPVC and to trace the course of the anomalous pulmonary venous connection, the direction of the inter-atrial shunt, enlargement of right atrium (RA) and right ventricle (RV), superior and inferior vena cava. All pediatric patients underwent surgical repair. The results of echocardiography were compared with surgical findings. RESULT: A total of 28 consecutive pediatric patients with suspected TAPVC were included in this study. The TAPVC diagnosis was confirmed in 26 cases after surgery, partial anomalous pulmonary venous connection (PAPVC) in one case, and Cor Triatriatum and possible TAPVC in another. The diagnostic accuracy of TAPVC by echocardiography in the study was 92.86%. There were 17 supracardiac TAPVC, 11 intracardiac TAPVC. In all patients, enlargement of the RA and RV, inter-atrial right-to-left shunt via atrial septal defects were documented in parasternal and subcostal views. Common pulmonary vein or four pulmonary vein direct to RA or via coronary sinus to RA were the draining sites of intracardiac TAPVC. The enlargement of left innominate vein-right superior vena cava draining to RA was seen in supracardiac TAPVC. CONCLUSION: A combination of suprasternal and subcostal multi-views in echocardiography can increase the diagnostic accuracy of TAPVC in pediatric patients.

Abnormalities, Multiple↗

[Liver transplantation for treating hepatocellular carcinoma].

OBJECTIVE: To evaluate the role of orthotopic liver transplantation (OLT) in treating hepatocellular carcinoma (HCC). METHODS: Data of 92 consecutive orthotopic liver transplantations (OLTs) performed during January 1999 and February 2005 at our institution were analyzed. RESULTS: Of the 92 recipients, 8 HCC patients were stage I, 13 were stage II, 12 stage III and 59 stage IV (UICC TNM staging system). Overall 1-, 2-, 3-, 5-year patient survival rates were 65.3%, 27.0%, 20.0%, and 6.9%, respectively. When OLT indications were considered, best recipients survival was obtained in stage I patients (100.0%, 100.0%, 66.7%, and 50.0% at 1, 2, 3, and 5 years, respectively) and stage II patients (85.7%, 66.7%, and 66.7% at 1, 2 and 3 years, respectively). Whereas, 1, 2, 3 and 5-year recipients survival rates were 50.0%, 0, 0, 0 in stage III patients, and 58.1%, 20.0%, 13.0% and 5.0% in stage IV patients. CONCLUSIONS: The prognosis of different stages of HCC patients who underwent OLT was significantly different. The OLT recipients with HCC should be strictly selected. Long-term recipient survival could be obtained in stage I and stage II patients.

Adult↗

[Cyclosporine microemulsion C2 monitoring in Chinese adult liver transplant recipients: a preliminary randomized control trial].

OBJECTIVE: To evaluate the safety and reliability of cyclosporine microemulsion (CsA-ME) C(2) monitoring and to determine the target level of C(2) in Chinese adult liver transplant recipients. METHODS: 53 Chinese adult liver transplant recipients were randomly divided into three groups (group C(0), n = 17; group high level C(2), n = 18; group low level C(2), n = 18). Blood chemistry reflecting heart, liver and renal function and CsA level were examined at certain interval during follow-up. The change of immune status and episodes of rejection were also observed closely. RESULTS: The group low level C(2) had the lowest CsA oral dose (2.51 +/- 0.37 mg/kg/d), and had significant difference compared with the other groups (P < 0.01). The best liver, heart and renal function was observed in group low level C(2). The CD(4)(+)/CD(8)(+) ratio of group low level C(2) was 1.04 +/- 0.68, which had no significant difference with C(0) group. The rejection incidence of the three groups had no significant difference. group low level C(2) had highest clinical benefit ratio (72.22%), while the clinical benefit of group high level C(2) is the lowest (11.11%). CONCLUSIONS: With rational target level, C(2) monitoring can show us the proper oral dose of CsA which can decrease the side effects remarkably without rejection episodes increasing. The target level of C(2) in Chinese adult liver transplant recipients might be: 600-800 ng/ml 1 to 6 months posttransplant, 400-600 ng/ml 7-12 months posttransplant.

Administration, Oral↗

[The effect of stimulation of dendritic cell on HBV-epitopic cytotoxic T-lymphocyte].

OBJECTIVE: To observe the enhancement of cytotoxic T lymphocyte responses in patients with chronic hepatitis B following vaccination with dendritic cell stimulated by Poly (I:C) in vitro. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from whole blood by density gradient centrifugation on Ficoll-Hypaque, the adherent cells were cultured in the medium AIM-V contained recombinant human IL-4 and recombinant human GM-CSF. On day 7, one part of wells were added with Poly (I:C). On day 9, mature DCs (mDCs) were harvested and used to phenotype analysis. Both of the immature DCs and mature DCs were concultured with the autologous T cells for another two-three days. According to the source of dendritic cells concultured with the T cells, the subjects were divided into three groups: the T cells isolated from CHB group; the T cells stimulated by dendritic cells pulsed with HBcAg18-27 CTL epitope peptide group; the T cells stimulated by dendritic cells concultured with Poly (I:C) and pulsed with HBcAg18-27 CTL epitope peptide group. The function and frequency of HBV specific CTL were detected by Elispot (Enzyme-linked immunospot assay, Elispot) and tetramer staining. RESULTS: The average of percentage of HBV specific CD8(+) cells of total CD8(+) cells was 0.77% (0.45% approximately 1.74%) in the T cells isolated from 22 chronic hepatitis B patients and the average of the spots of antigen-specific IFN-gamma-releasing effector cells was 16 (9 approximately 28); The percentage of HBV specific CD8(+) cells of the T cells stimulated by dendritic cells pulsed with HBcAg18-27 CTL epitope peptide group rose to 1.92% (1.36% approximately 2.65%) and the average of the spots of antigen-specific IFN-gamma-releasing effector cells was 46 (30 approximately 67); while stimulated by dendritic cells added with Poly (I:C) and pulsed with HBcAg18-27 CTL epitope peptide, the percentage of HBV specific CD8(+) cells of total CD8(+) cells rose to 3.49% (2.02% approximately 4.60%) and the average of the spots was 98 (59 approximately 130). There was statistical difference between the results of Elispot and tetramer of the three groups (P < 0.01). CONCLUSION: The T lymphocyte of patients with chronic hepatitis B stimulated by the autologous dendritic cells may result in obtaining high percentage and functional antigen-specific T lymphocyte. The addition of Poly (I:C) which was used as maturation promoting factor in DC culture can enhance the function of DC significantly and can get even higher percentage antigen-specific T lymphocyte with enhanced function.

Adult↗

I've heard it all before: perceptual invariance represented by early cortical auditory-evoked responses.

Sensitivity to acoustic invariance is critical for establishing stable representations in a shifting world of sound. By recording early auditory cortical responses to complex sounds in human listeners and categorising these responses according to the maintenance or change of stimulus attributes across consecutive presentations, we show that repetition within a constantly varying acoustic context produces enhanced neural responding in auditory cortices.

Acoustic Stimulation↗