Transport Dynamics of Quark-Gluon Plasma in Perturbative QCD with Magnetic fields/Vorticity

In this defense, I present my research on transport dynamics of the quark-gluon plasma (QGP) with magnetic field and/or vorticity by using the thermal perturbative Quantum Chromodynamics(pQCD) approach. The first main topic focuses on studying the interplay between the QCD interactions and magnetic field, where an effective kinetic theory of the lowest Landau level quarks is formulated, from which the quark mass dependence of the finite electrical conductivity is found. Shear viscosity that governs the rate of momentum transfer, is also affected by the presence of the magnetic field. A full numerical result for the magnetic-dependent shear viscosity is provided. The second main topic will be on the spin dynamics of QGP, where a novel quantum kinetic description of the spin polarization of massive quarks is first formulated in the context of pQCD. This framework shows that the order of time scale of spin polarization is the same as that of charge transport and shear viscosity, which is not captured by usual classical kinetic theory. In the third topic, I will introduce our novel construction of the non-dissipative second-order hydrodynamics for a slowly rotating fluid. New transport coefficients arise and are constrained by the second law of thermodynamics. We demonstrate that the extension of hydrodynamics by the spin variable is equivalent to modifying conventional hydrodynamics by a set of second-order terms satisfying the relations we derived. We point out that a novel contribution to the heat current orthogonal to vorticity and temperature gradient reminiscent of the thermal Hall effect is constrained by the second law

Blockade of Asparagine Endopeptidase Inhibits Cancer Metastasis

Asparagine endopeptidase (AEP), also called legumain, is highly expressed in various solid tumors, promoting cancer cell invasion, migration, and metastasis. It has been proposed to be a prognostic marker and therapeutic target for cancer treatment. However, an effective nonpeptide, small-molecule inhibitor against this protease has not yet been identified. Here we show that a family of xanthine derivatives selectively inhibit AEP and suppress matrix metalloproteinase (MMP) cleavage, leading to the inhibition of cancer metastasis. Through structure–activity relationship (SAR) analysis, we obtained an optimized lead compound (<b>38u</b>) that represses breast cancer invasion and migration. Chronic treatment of nude mice, which had been inoculated with MDA-MB-231 cells, with inhibitor <b>38u</b> via oral administration robustly inhibits breast cancer lung metastasis in a dose-dependent manner, associated with blockade of MMP-2 by AEP. Therefore, our study supports that <b>38u</b> might act as a potent and specific AEP inhibitor useful for cancer treatment

Table_1_Clinical safety and possible efficacy of tirofiban in combination with intravenous thrombolysis by recombinant tissue plasminogen activator for early treatment of capsular warning syndrome (CWS).DOCX

The purpose of this study was to assess the efficacy and safety of the combination of tirofiban with intravenous thrombolysis (IVT) in treating patients with capsular warning syndrome (CWS) who failed to respond to the treatment of intravenous thrombolysis alone. Tirofiban was approved for the treatment of CWS patients with fluctuating symptoms or no substantial improvement after intravenous thrombolysis within 24 h in our hospital from October 2019 to June 2021. Patients were evaluated with the National Institutes of Health Stroke Scale (NIHSS) at admission, at 72 h post-thrombolysis, at 1-week, and at 3-months with the modified Rankin Scales (MRS) score. A total of 12 patients received tirofiban and eight patients received control treatment with a history of CWS in our cohort. Among the patients, 13 patients smoked more than one pack of cigarettes a day, 17 had hypertension, 17 had hypercholesterolemia, 7 had diabetes, 1 had the history of cerebral infarction, 2 had atrial fibrillation, 7 had mild big vascular stenosis, 13 had lesions of the perforating branch by imaging, and 19 had acute capsular infarction. In both the tirofiban and control groups, NIHSS scores were significantly reduced after intravenous thrombolysis or 1-week after onset compared with before intravenous thrombolysis (P < 0.001). Before and after intravenous thrombolysis, there were no differences between the tirofiban group and control group (P = 0.970, P = 0.384, respectively). The tirofiban group, however, showed remarkably lower scores in both 1-week NIHSS and 3-month MRS than the control (P = 0.012, P = 0.003, respectively). Our study revealed that tirofiban did not increase the risk of hemorrhage and had favorable clinical efficacy as a remedial treatment for CWS patients with poor prognosis for intravenous thrombolysis, therefore indicating great potential for broader use.</p

SIRT3 interacts with LDHA and regulates LDHA activity through deacetylation.

<p>A, LDHA activity was measured in AGS and SGC-7901 cells with SIRT3 overexpression or knockdown and represented as relative activity normalized by control (NC or Scr). LDHA expression in SIRT3 overexpression and knockdown AGS cells was analyzed by immunoblotting. B, co-localization of SIRT3 and LDHA was detected by immunostaining in AGS cells with anti-SIRT3 (green) and anti-LDHA (red) antibodies. Nuclei were conterstained with DAPI (blue). Scale bar, 5 μm. C, LDHA was immunoprecipitated (IP) followed by western blot (WB) of LDHA or SIRT3, or reverse, in AGS gastric cancer cells. IP with non-immune goat IgG serves as a negative control, and immunoblotting of total cell lysates (input) serves as the IP equal loading control. D, SIRT3-enhanced deacetylation of LDHA in AGS cells was detected by IP with anti-LDHA followed by western blot with anti-LDHA and anti-acetyl-lysine antibodies. Western blot of total cell lysates with SIRT3 antibody to show the expression of transfected protein. E, LDHA enzymatic activity was measured using commercial bovine heart L-Lactic dehydrogenase and recombinant human SIRT3 enzyme with/without SIRT3 inhibitor nicotinamide. F, LDHA enzymatic activity was measured using commercial recombinant human SIRT3 enzyme and immunoprecipitated LDHA from AGS cells transfected with K5Q/R or K318Q/R mutant LDHA with/without SIRT3 inhibitor nicotinamide and presented as relative enzyme activity normalized by wild type LDHA without SIRT3 inhibitor. In A, E and F, data are presented as mean ± S.E. (n = 5; *, <i>p</i> < 0.05; **, <i>p</i> < 0.01).</p

SIRT3 Enhances Glycolysis and Proliferation in SIRT3-Expressing Gastric Cancer Cells

<div><p>SIRT3 is a key NAD⁺-dependent protein deacetylase in the mitochondria of mammalian cells, functioning to prevent cell aging and transformation via regulation of mitochondrial metabolic homeostasis. However, SIRT3 is also found to express in some human tumors; its role in these SIRT3-expressing tumor cells needs to be elucidated. This study demonstrated that the expression of SIRT3 was elevated in a group of gastric cancer cells compared to normal gastric epithelial cells. Although SIRT3 expression levels were increased in the gastric tumor tissues compared to the adjacent non-tumor tissues, SIRT3 positive cancer cells were more frequently detected in the intestinal type gastric cancers than the diffuse type gastric cancers, indicating that SIRT3 is linked with subtypes of gastric cancer. Overexpression of SIRT3 promoted cell proliferation and enhanced ATP generation, glucose uptake, glycogen formation, MnSOD activity and lactate production, which were inhibited by SIRT3 knockdown, indicating that SIRT3 plays a role in reprogramming the bioenergetics in gastric tumor cells. Further analysis revealed that SIRT3 interacted with and deacetylated the lactate dehydrogenase A (LDHA), a key protein in regulating anaerobic glycolysis, enhancing LDHA activity. In consistence, a cluster of glycolysis-associated genes was upregulated in the SIRT3-overexpressing gastric tumor cells. Thus, in addition to the well-documented SIRT3-mediated mitochondrial homeostasis in normal cells, SIRT3 may enhance glycolysis and cell proliferation in SIRT3-expressing cancer cells.</p></div

SIRT3 promotes aggressive characteristics of gastric cancer cells.

<p>A, cell growth of AGS and SGC-7901 cells with SIRT3 overexpression or knockdown was calculated on days 2, 4, 6 and 8 after cell plating. SIRT3 expression in stable transfectants was confirmed by western blot. B, clonogenicity of AGS and SGC-7901 cells with SIRT3 overexpression or knockdown was measured and presented as the fraction of control transfectants (NC or Scr). C, Overexpression of SIRT3 promoted tumor burden in vivo. SGC-7901 cells with SIRT3 overexpression (left panel) or knockdown (right panel) were subcutaneously injected into right flank of the nude mice with the relative control cells (NC or Scr) into the left flank. Xenograft tumors were excised and weighed at the 28^th day after cell inoculation. Images of right panel showed xenograft tumors in vivo at the end of the experiment. Images of up right corner showed the dissected tumors from each group. The ranges and means of tumor weights of each group were presented in right panel as mean ± S.E. (n = 5; *, <i>p</i> < 0.05; **, <i>p</i> < 0.01). SIRT3, SIRT3 overexpression; shSIRT3, SIRT3 knockdown; NC (negative control; empty pcDNA3.1) and Scr (scramble shRNA; pGPH1/GFP/Neo-shRNA) serve as controls for pcDNA3.1-SIRT3 and pGPH1/GFP/Neo-shSIRT3 respectively.</p

Overexpression of SIRT3 enhances glycolysis in gastric cancer cells.

<p>Glucose uptake, lactate production and glycogen formation were measured in AGS (A, C, E) and SGC-7901 (B, D, F) cells with SIRT3 overexpression or knockdown. All data are presented as mean ± S.E. (n = 3; *, <i>p</i> < 0.05; **, <i>p</i> < 0.01).</p

DataSheet_1_Non-invasive detection of lymphoma with circulating tumor DNA features and protein tumor markers.pdf

BackgroundAccording to GLOBOCAN 2020, lymphoma ranked as the 9th most common cancer and the 12th leading cause of cancer-related deaths worldwide. Traditional diagnostic methods rely on the invasive excisional lymph node biopsy, which is an invasive approach with some limitations. Most lymphoma patients are diagnosed at an advanced stage since they are asymptomatic at the beginning, which has significantly impacted treatment efficacy and prognosis of the disease.MethodThis study assessed the performance and utility of a newly developed blood-based assay (SeekInCare) for lymphoma early detection. SeekInCare utilized protein tumor markers and a comprehensive set of cancer-associated genomic features, including copy number aberration (CNA), fragment size (FS), end motif, and lymphoma-related virus, which were profiled by shallow WGS of cfDNA.ResultsProtein marker CA125 could be used for lymphoma detection independent of gender, and the sensitivity was 27.8% at specificity of 98.0%. After integrating these multi-dimensional features, 77.8% sensitivity was achieved at specificity of 98.0%, while its NPV and PPV were both more than 92% for lymphoma detection. The sensitivity of early-stage (I-II) lymphoma was up to 51.3% (47.4% and 55.0% for stage I and II respectively). After 2 cycles of treatment, the molecular response of SeekInCare was correlated with the clinical outcome.ConclusionIn summary, a blood-based assay can be an alternative to detect lymphoma with adequate performance. This approach becomes particularly valuable in cases where obtaining tissue biopsy is difficult to obtain or inconclusive.</p

Table_1_Non-invasive detection of lymphoma with circulating tumor DNA features and protein tumor markers.xlsx

BackgroundAccording to GLOBOCAN 2020, lymphoma ranked as the 9th most common cancer and the 12th leading cause of cancer-related deaths worldwide. Traditional diagnostic methods rely on the invasive excisional lymph node biopsy, which is an invasive approach with some limitations. Most lymphoma patients are diagnosed at an advanced stage since they are asymptomatic at the beginning, which has significantly impacted treatment efficacy and prognosis of the disease.MethodThis study assessed the performance and utility of a newly developed blood-based assay (SeekInCare) for lymphoma early detection. SeekInCare utilized protein tumor markers and a comprehensive set of cancer-associated genomic features, including copy number aberration (CNA), fragment size (FS), end motif, and lymphoma-related virus, which were profiled by shallow WGS of cfDNA.ResultsProtein marker CA125 could be used for lymphoma detection independent of gender, and the sensitivity was 27.8% at specificity of 98.0%. After integrating these multi-dimensional features, 77.8% sensitivity was achieved at specificity of 98.0%, while its NPV and PPV were both more than 92% for lymphoma detection. The sensitivity of early-stage (I-II) lymphoma was up to 51.3% (47.4% and 55.0% for stage I and II respectively). After 2 cycles of treatment, the molecular response of SeekInCare was correlated with the clinical outcome.ConclusionIn summary, a blood-based assay can be an alternative to detect lymphoma with adequate performance. This approach becomes particularly valuable in cases where obtaining tissue biopsy is difficult to obtain or inconclusive.</p

Genes potentially regulated by SIRT3 in gastric cancer cells.

<p>Relative mRNA levels of Glut1, HK2, MCT1 and MCT4 were measured by qRT-PCR in AGS (A) and SGC-7901 (B) cells with SIRT3 overexpression or knockdown. Data are presented as mean ± S.E. (n = 3; *, <i>p</i> < 0.05; **, <i>p</i> < 0.01). (C) Schematic presentation of the potential mechanism by which SIRT3 triggers the cell growth. SIRT3 deacetylates and activates LDHA causing enhanced LDHA activity and cellular bioenergetics, which together with SIRT3-mediated MnSOD activation enhances cell proliferation.</p