Biomedical subjects

Shijie Liu

Publications and source records attributed to Shijie Liu.

9 recordsLinked to original sources

PubMed2026

YAP Promotes Microtubule Growth to Facilitate Sarcomere Disassembly in Adult Cardiomyocytes.

BACKGROUND: Mature mammalian cardiomyocytes (CMs) develop compact sarcomeric structures that inhibit proliferation. Consequently, CMs must dedifferentiate to a fetus-like state, which is accompanied by sarcomere disassembly, to enable successful cytokinesis. However, the regulation and coordination of CM dedifferentiation, cell cycle progression, and sarcomere reorganization remain unclear. METHODS: We generated adenovirus and adeno-associated virus (MyoAAV) vectors expressing YAP5SA and YAP5SA-S94A under Xon control for LMI070-inducible protein expression. We also developed MyoAAV-cTnT-Tuba1b-shRNA-miR30 for cardiomyocyte-specific knockdown of Tuba1b. These tools were used to investigate CM dedifferentiation and proliferation and sarcomere disassembly. We also performed Cleavage Under Targets and Release Using Nuclease to map the genome-wide binding sites of YAP5SA and YAP5SA-S94A in combination with RNA sequencing to identify YAP target genes. In addition, time-course live-imaging analysis was used to evaluate microtubule and sarcomere dynamics in adult CMs. RESULTS: We show that microtubule expression and network density decline with cardiac maturation. Overexpression of YAP5SA, a constitutively active YAP mutant, promotes microtubule growth by stabilizing microtubule dynamics, leading to CM dedifferentiation, cell cycle re-entry, and sarcomere disassembly. In contrast, colchicine blocks these processes and significantly attenuates YAP-induced cardiac regeneration. Live imaging reveals a distinct mode of sarcomere disassembly driven by enhanced microtubule polymerization, wherein microtubule plus-ends directly interact with α-actinin and displace α-actinin fragments, thereby facilitating sarcomere breakdown. Furthermore, the YAP5SA-S94A mutation, which disrupts the YAP and TEA domain interaction, significantly reduces YAP5SA-induced microtubule growth, sarcomere disassembly, and cell cycle activity. Mechanistically, cleavage under targets and release using nuclease combined with RNA sequencing identified direct YAP targets, including Ajuba and Tuba1b, which are critical for microtubule growth. CM-specific knockdown of Tuba1b attenuates YAP-driven sarcomere disassembly. CONCLUSIONS: These findings identify microtubule networks as an essential regulator modulating CM dedifferentiation and sarcomere reorganization, which is critical for CM cytokinesis and cardiac regenerative repair.

Animals↗

PubMed2026

Big data analytics for CLEC5A dynamics based on single cell genomics and proteomics reveal its diverse functions in human diseases.

BACKGROUND: CLEC5A (C-type lectin domain family 5 member A) is an innate immune receptor implicated in inflammatory signaling, contributing to hyperinflammatory responses in infections and sterile inflammation. However, CLEC5A dynamics in human diseases remain to be identified. Here, we systematically characterized CLEC5A dynamics in humans across cells, tissues, and disease states, and to explore the functional significance of CLEC5A in macrophage activation based on single-cell genomics. METHODS: With multi-omics (scRNA-seq, proteomics and big data analytics), we analyzed extensive human transcriptomic datasets (>42,000 samples) to profile CLEC5A expression by cell type, tissue, and disease. Single-nucleus RNA-seq (snRNA-seq) from pediatric congenital heart disease and a virtual CLEC5A gene knockout were also performed to characterize CLEC5A dynamics in humans. RESULTS: CLEC5A is highly enriched in innate immune cells, particularly in macrophages and neutrophils. Baseline CLEC5A in most tissues is low, but it is markedly upregulated in inflammatory and infectious diseases. CLEC5A expression has sex-specific differences in certain organs. Single-cell analysis showed that CLEC5A can be considered novel marker of proinflammatory macrophages with elevated cytokine production, antigen presentation, and impaired phagocytosis. Virtual CLEC5A knockout analysis identified coordinated perturbation of immune-regulatory pathways and overlapping genes linking CLEC5A to macrophage activation networks. CONCLUSION: CLEC5A is predominantly expressed in myeloid cells and acts as a key amplifier of inflammation in human diseases. Our findings highlight CLEC5A as a potential biomarker and therapeutic target in myeloid-driven hyperinflammatory conditions, warranting further experimental and translational validation.

Humans↗

PubMed2006

Tumor suppressor PTEN affects tau phosphorylation: deficiency in the phosphatase activity of PTEN increases aggregation of an FTDP-17 mutant Tau.

BACKGROUND: Aberrant hyperphosphorylation of tau protein has been implicated in a variety of neurodegenerative disorders. Although a number of protein kinases have been shown to phosphorylate tau in vitro and in vivo, the molecular mechanisms by which tau phosphorylation is regulated pathophysiologically are largely unknown. Recently, a growing body of evidence suggests a link between tau phosphorylation and PI3K signaling. In this study, phosphorylation, aggregation and binding to the microtubule of a mutant frontal temporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) tau in the presence of tumor suppressor PTEN, a major regulatory component in PI3K signaling, were investigated. RESULTS: Phosphorylation of the human mutant FTDP-17 tau, T40RW, was evaluated using different phospho-tau specific antibodies in the presence of human wild-type or phosphatase activity null mutant PTEN. Among the evaluated phosphorylation sites, the levels of Ser214 and Thr212 phospho-tau proteins were significantly decreased in the presence of wild-type PTEN, and significantly increased when the phosphatase activity null mutant PTEN was ectopically expressed. Fractionation of the mutant tau transfected cells revealed a significantly increased level of soluble tau in cytosol when wild-type PTEN was expressed, and an elevated level of SDS-soluble tau aggregates in the presence of the mutant PTEN. In addition, the filter/trap assays detected more SDS-insoluble mutant tau aggregates in the cells overexpressing the mutant PTEN compared to those in the cells overexpressing wild-type PTEN and control DNA. This notion was confirmed by the immunocytochemical experiment which demonstrated that the overexpression of the phosphatase activity null mutant PTEN caused the mutant tau to form aggregates in the COS-7 cells. CONCLUSION: Tumor suppressor PTEN can alleviate the phosphorylation of the mutant FTDP-17 tau at specific sites, and the phosphatase activity null PTEN increases the mutant tau phosphorylation at these sites. The changes of the tau phosphorylation status by ectopic expression of PTEN correlate to the alteration of the mutant tau's cellular distribution. In addition, the overexpression of the mutant PTEN can increase the level of the mutant tau aggregates and lead to the formation of visible aggregates in the cells.

Journal Article↗

PubMed2006

Electric field enhancement in guided-mode resonance filters.

Electric fields inside guided-mode resonance filters (GMRFs) may be intensified by resonance effects. The electric field enhancement is investigated in two GMRFs: one is resonant at normal incidence, the other at oblique incidence. It is shown that the two GMRFs exhibit different behaviors in their electric enhancement. Differences between the electric field distributions of the two GMRFs arise because coupling between counterpropagating modes occurs in the first case. It is also shown that the order of the electric field of maximum amplitude can be controlled by modulation of the dielectric constant of the grating.

Journal Article↗

PubMed2006

Extended bidirectional reflectance distribution function for polarized light scattering from subsurface defects under a smooth surface.

By introducing the scattering probability of a subsurface defect (SSD) and statistical distribution functions of SSD radius, refractive index, and position, we derive an extended bidirectional reflectance distribution function (BRDF) from the Jones scattering matrix. This function is applicable to the calculation for comparison with measurement of polarized light-scattering resulting from a SSD. A numerical calculation of the extended BRDF for the case of p-polarized incident light was performed by means of the Monte Carlo method. Our numerical results indicate that the extended BRDF strongly depends on the light incidence angle, the light scattering angle, and the out-of-plane azimuth angle. We observe a 180 degrees symmetry with respect to the azimuth angle. We further investigate the influence of the SSD density, the substrate refractive index, and the statistical distributions of the SSD radius and refractive index on the extended BRDF. For transparent substrates, we also find the dependence of the extended BRDF on the SSD positions.

Journal Article↗

PubMed2002

[Effects of exposure to asbestos on plasma activity of glutathione S-transferases].

OBJECTIVE: To understand the effects of exposure to asbestos and GSTM1 genotypes on plasma activity of glutathione S-transferases (GSTs). METHODS: Ninety-four workers exposed to asbestos and 51 controls were selected, and their general information, occupational history and personal behavior were collected by questionnaire. Venous blood specimen was collected from each of them and plasma was separated for detection of GSTs activity and lymphocytes for DNA extraction and GSTM1 genotyping. RESULTS: Plasma activity of GSTs in the asbestos-exposed workers (23.0 +/- 6.9) U/L was significantly lower than that in the controls (32.6 +/- 11.8) U/L, which declined with the length of employment in asbestos industry and the increase of cumulated dose of asbestos. Stratification of workers by GSTM1 genotypes showed that plasma activity of GSTs in asbestos-exposed workers with GSTM1+/+ or GSTM1-/- were (24.0 +/- 6.1) and (22.5 +/- 7.3) U/L, respectively, lower than those in the controls with the same genotypes (38.1 +/- 13.2) and (26.8 +/- 6.6) U/L. Plasma activity of GSTs in the control workers with GSTM-/- was significantly lower than in those with GSTM+/+, and, so did in asbestos-exposed workers, but without statistically significant difference. CONCLUSION: Exposure to asbestos could significantly decrease plasma activity of GSTs, and GSTM1 genotypes could affect on the activity of GSTs in the control workers, which was not so obvious in asbestos-exposed workers.

Adult↗

PubMed2002

[Effects of chrysotile asbestos on the activities of cytochrome P4501A1 and glutathione S-transferase in A549 cell line].

OBJECTIVE: To study the effects of chrysotile on the activities of some enzymes for xenobiotics metabolism. METHODS: UICC chrysotile (UC) and China Mangya chrysotile (MC) asbestos fibers were used at different doses (0, 25, 50, 100, 200 mg/L) to study its effects on the activities of cytochrome P4501A1 and glutathione S-transferase (GST) in A549 cell line. Also, the effects of chrysotile on the activities of CYP1A1 and GST induced by benzo(a)pyrene were studied. RESULTS: The activity of EROD increased slowly with the increasing dose of UC, as A549 cells were incubated with UC for 24 h, and EROD activity increased by 40% at a dose of 200 mg/L UC. However, activity of EROD decreased by 32% with 48 h incubation at the same dose, indicating that lower dose of UC and short time could induce the activity of EROD in A549 cells, whereas higher doses and long time could inhibit its activity. MC exhibited a multiphasic effects on the activity of EROD, whether at a dose of 25 mg/L for 24 h or 48 h all gave the strongest induction, 1.86 times or 1.28 times as controls, respectively. However, EROD activity decreased with the increases in MC doses and incubation time, with the lowest as 35% of the controls. The effect of UC on GST activity was not so obvious, with the highest as the increase in its activity by 20%. The highest induction of MC to GST activity was at a dose of 25 mg/L, 2, 5 times as that in controls. With the increases in its doses, effects of MC on GTS activity became inhibition from induction, like that on EROD activity. MC at a dose of 200 mg/L could lower the activity of GST by 18.7%. A549 cells were incubated with chrysotile fiber for 24 h firstly, and then incubated with benzo(a)pyrene to induce the activities of EROD and GST. The results showed that neither UC nor MC could affect the activity of EROD induced by benzo(a)pyrene. However, UC at a dose of 200 mg/L and MC at 100 mg/L could increase the activity of GST induced by benzo(a)pyrene. CONCLUSION: Chrysotile at different doses or its different types showed varied effects on the activities of EROD and GST in A549 cell lines, probably because of different physicochemical characteristics and surface activity of two kinds of asbestos.

Asbestos, Serpentine↗

PubMed2002

[The relationship between glutathione S-transferase M1 genotypes and lipid peroxidation in asbestos workers].

OBJECTIVE: To study the relationship between glutathione S-transferase M1 (GSTM1) genotypes and lipid peroxidation of asbestos workers. METHODS: 94 asbestos workers and 51 controls were selected as subjects. The general information, occupational history and individual habits were collected by questionnaires in all participants. The venous blood was sampled and the plasma was separated for the detection of malondialdehyde (MDA) level and lymphocytes for DNA isolation and GSTM1 genotyping. RESULTS: MDA level was significantly higher in asbestos workers [(0.283 +/- 0.054) nmol/L] than that in controls [(0.163 +/- 0.053) nmol/L, P < 0.01], however, neither duration of exposure nor accumulated asbestos exposure dose was related to MDA levels; MDA levels in control workers with GSTM1 +/- genotype [(0.190 +/- 0.034) nmol/L] were significantly higher than that in control workers with GSTM1 +/+ genotype [(0.138 +/- 0.055) nmol/L, P < 0.01]. Among asbestos workers, the same trend could be found, but the differences was not significant(P > 0.05). When the workers were stratified by duration of exposure or accumulated asbestos exposure dose, MDA levels in individuals with GSTM1 -/- genotype were also higher than those with GSTM1 +/+ genotype, but the differences were also not significant(P > 0.05). CONCLUSION: Both exposure to asbestos and deficiency of GSTM1 genotype were related to lipid peroxidation in workers, but the role of the former may be more important than that of the latter.

Asbestos↗

PubMedDate not supplied

Comparison of in vitro disc diffusion and time kill-kinetic assays for the evaluation of antimicrobial wound dressing efficacy.

There is a plethora of new silver-containing dressings on the market today. Various manufacturers attempt to show that their dressings are the most efficacious and therefore should be preferentially employed by health care workers based on the results of their in vitro tests. However, there have been no studies that clearly identify which tests are appropriate for comparison purposes. The purpose of this study was to determine which in vitro test is most appropriate for evaluating the antimicrobial efficacy of silver-containing dressings. This was done by testing seven silver-containing dressings and two non-silver-containing topical agents against 17 clinically relevant microorganisms using zone of inhibition assays and time-kill kinetic assays in complex media. The results for the two assays were then correlated to determine whether the methods generated similar results. It was determined that the two methods do not correlate at all. This is most likely a result of the silver interacting with the media in the zone of inhibition test, thus invalidating the results of this test. We therefore conclude that zone of inhibition data generated for silver-containing dressings is of little value when assessing antimicrobial efficacy and that time-kill assays are of greater use.

Administration, Topical↗