Application of the magnetic resonance 3D multiecho Dixon sequence for quantifying hepatic iron overload and steatosis in patients with thalassemia.

OBJECTIVE: To investigate the feasibility and diagnostic efficacy of a 3D multiecho Dixon (qDixon) research application for simultaneously quantifying the liver iron concentration (LIC) and steatosis in thalassemia patients. MATERIALS AND METHODS: This prospective study enrolled participants with thalassemia who underwent 3 T MRI of the liver for the evaluation of hepatic iron overload. The imaging protocol including qDixon and conventional T2* mapping based on 2D multiecho gradient echo (ME GRE) sequences respectively. Regions of interest (ROIs) were drawn in the liver on the qDixon maps to obtain R2* and proton density fat fraction (PDFF). The reference R2* value was measured and calculated on conventional T2* mapping using the CMRtools software. Correlation analysis, Linear regression analysis, and Bland-Altman analysis were performed. RESULTS: 84 patients were finally included in this study. The median R2*-ME-GRE was 366.97 (1/s), range [206.68 (1/s), 522.20 (1/s)]. 8 patients had normal hepatic iron deposition, 16 had Insignificant, 42 had mild, 18 had moderate. The median of R2*-qDixon was 376.88 (1/s) [219.33 (1/s), 491.75 (1/s)]. A strong correlation was found between the liver R2*-qDixon and the R2*-ME-GRE (r = 0.959, P < 0.001). The median value of PDFF was 1.76% (1.10%, 2.95%). 8 patients had mild fatty liver, and 1 had severe fatty liver. CONCLUSION: MR qDixon research sequence can rapidly and accurately quantify liver iron overload, that highly consistent with the measured via conventional GRE sequence, and it can also simultaneously detect hepatic steatosis, this has great potential for clinical evaluation of thalassemia patients.

An Efficient Approach to the Accurate Prediction of Mutational Effects in Antigen Binding to the MHC1.

The major histocompatibility complex (MHC) can recognize and bind to external peptides to generate effective immune responses by presenting the peptides to T cells. Therefore, understanding the binding modes of peptide-MHC complexes (pMHC) and predicting the binding affinity of pMHCs play a crucial role in the rational design of peptide vaccines. In this study, we employed molecular dynamics (MD) simulations and free energy calculations with an Alanine Scanning with Generalized Born and Interaction Entropy (ASGBIE) method to investigate the protein-peptide interaction between HLA-A*02:01 and the G9209 peptide derived from the melanoma antigen gp100. The energy contribution of individual residue was calculated using alanine scanning, and hotspots on both the MHC and the peptides were identified. Our study shows that the pMHC binding is dominated by the van der Waals interactions. Furthermore, we optimized the ASGBIE method, achieving a Pearson correlation coefficient of 0.91 between predicted and experimental binding affinity for mutated antigens. This represents a significant improvement over the conventional MM/GBSA method, which yields a Pearson correlation coefficient of 0.22. The computational protocol developed in this study can be applied to the computational screening of antigens for the MHC1 as well as other protein-peptide binding systems.

PLCD3 inhibits apoptosis and promotes proliferation, invasion and migration in gastric cancer.

Gastric cancer (GC) is a heterogeneous disease whose development is accompanied by alterations in a variety of pathogenic genes. The phospholipase C Delta 3 enzyme is a member of the phospholipase C family, which controls substance transport between cells in the body. However, its role in gastric cancer has not been discovered. The purpose of this study was to investigate the expression and mechanism of action of PLCD3 in connection to gastric cancer. By Western blot analysis and immunohistochemistry, PLCD3 mRNA and protein expression levels were measured, with high PLCD3 expression suggesting poor prognosis. In N87 and HGC-27 cells, the silencing of PLCD3 using small interfering RNA effectively induced apoptosis and inhibited tumor cell proliferation, invasion, and migration. Conversely, overexpression of PLCD3 using overexpressed plasmids inhibited apoptosis in AGS and BGC-823 cells and promoted proliferation, migration, and invasion. In order to investigate the underlying mechanisms, we conducted further analysis of PLCD3, which indicates that this protein is closely related to the cell cycle and EMT. Additionally, we found that overexpression of PLCD3 inhibits apoptosis and promotes the development of GC cells through JAK2/STAT3 signaling. In conclusion, PLCD3 inhibits apoptosis and promotes proliferation, invasion, and migration, which indicated that PLCD3 might serve as a therapeutic target for gastric cancer.

C-C Motif Chemokine Ligand 5 (CCL5) Promotes Irradiation-Evoked Osteoclastogenesis.

The imbalance that occurs in bone remodeling induced by irradiation (IR) is the disruption of the balance between bone formation and bone resorption. In this study, primary osteocytes (OCYs) of femoral and tibial origin were cultured and irradiated. It was observed that irradiated OCY showed extensive DNA damage, which led to the initiation of a typical phenotype of cellular senescence, including the secretion of senescence-associated secretory phenotype (SASP), especially the C-C motif chemokine ligand 5 (CCL5). In order to explore the regulation of osteoclastogenic potential by IR-induced senescent OCYs exocytosis factor CCL5, the conditioned medium (CM) of OCYs was co-cultured with RAW264.7 precursor cells. It was observed that in the irradiated OCY co-cultured group, the migration potential increased compared with the vehicle culture group, accompanied by an enhancement of typical mature OCs; the expression of the specific function of enzyme tartrate-resistant acid phosphatase (TRAP) increased; and the bone-destructive function was enhanced. However, a neutralizing antibody to CCL5 could reverse the extra-activation of osteoclastogenesis. Accordingly, the overexpression of p-STAT3 in irradiated OCY was accompanied by CCL5. It was concluded that CCL5 is a potential key molecule and the interventions targeting CCL5 could be a potential strategy for inhibiting osteoclastogenesis and restoring bone remodeling.

A multicenter study on the quantification of liver iron concentration in thalassemia patients by means of the MRI T2* technique.

Objective: To investigate the feasibility and accuracy of quantifying liver iron concentration (LIC) in patients with thalassemia (TM) using 1.5T and 3T T2* MRI. Methods: 1.5T MRI T2* values were measured in 391 TM patients from three medical centers: the T2* values of the test group were combined with the LIC (LICF) provided by FerriScan to construct the curve equation. In addition, the liver 3T MRI liver T2* data of 55 TM patients were measured as the 3T group: the curve equation of 3T T2* value and LICF was constructed. Results: Based on the test group LICF (0.6-43 mg/g dw) and the corresponding 1.5T T2* value, the equation was LICF = 37.393T2*∧(-1.22) (R2 = 0.971; P < 0.001). There was no significant difference between LICe - 1.5T and LICF in each validation group (Z = -1.269, -0.977, -1.197; P = 0.204, 0.328, 0.231). There was significant consistency (Kendall's W = 0.991, 0.985, 0.980; all P < 0.001) and high correlation (rs = 0.983, 0.971, 0.960; all P < 0.001) between the two methods. There was no significant difference between the clinical grading results of LICe - 1.5T and LICF in each validation group (χ2 = 3.0, 4.0, 2.0; P = 0.083, 0.135, 0.157), and there was significant consistency between the clinical grading results (Kappa's K = 0.943, 0.891, 0.953; P < 0.001). There was no statistical correlation between the LICF (≥14 mg/g dw) and the 3T T2* value of severe iron overload (P = 0.085). The LICF (2-14 mg/g dw) in mild and moderate iron overload was significantly correlated with the corresponding T2* value (rs = -0.940; P < 0.001). The curve equation constructed from LICF and corresponding 3T T2* values in this range is LICF = 18.463T2*∧(-1.142) (R2 = 0.889; P < 0.001). There was no significant difference between LICF and LICe - 3T in the mild to moderate range (Z = -0.523; P = 0.601), and there was a significant correlation (rs = 0.940; P < 0.001) and significant consistency (Kendall's W = 0.970; P = 0.008) between them. LICe - 3T had high diagnostic efficiency in the diagnosis of severe, moderate, and mild liver iron overload (specificity = 1.000, 0.909; sensitivity = 0.972, 1.000). Conclusion: The liver iron concentration can be accurately quantified based on the 1.5T T2* value of the liver and the specific LIC-T2* curve equation. 3T T2* technology can accurately quantify mild-to-moderate LIC, but it is not recommended to use 3T T2* technology to quantify higher iron concentrations.

Multi-echo Dixon and breath-hold T2-corrected multi-echo single-voxel MRS for quantifying hepatic iron overload in rabbits.

BACKGROUND: Three-dimensional (3D) multi-echo-Dixon (ME-Dixon) and breath-hold T2-corrected multi-echo single-voxel MR spectroscopy (HISTO) can simultaneously quantify liver fat and liver iron. However, their diagnostic efficacy and application scope for quantitative iron in co-existing fatty liver have not been adequately evaluated. PURPOSE: To evaluate the accuracy of ME-Dixon and HISTO for quantitative analysis of hepatic iron in rabbits with iron deposition and fatty liver using liver-iron concentration (LIC) as a reference standard. MATERIAL AND METHODS: ME-Dixon, HISTO, and conventional two-dimensional multi-echo gradient echo (GRE) sequences were performed on 42 rabbits. The following parameters were calculated: R2* from ME-Dixon and GRE; proton density fat fraction (PDFF) from the ME-Dixon, HISTO (normal TE range), and HISTO-H (extended TE range); and R2_water from HISTO and HISTO-H. The LIC and liver-fat concentration (LFC) were measured through chemical analysis, and their relationship with the MRI parameters were assessed. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate the diagnostic efficiency. RESULTS: LIC was significantly correlated with R2_HISTO-H, R2*_Dixon, and R2*_GRE (r = 0.858, 0.910, 0.931, respectively; P < 0.001) and weakly with R2_HISTO (r = 0.424; P = 0.008). A strong correlation was also observed between the LFC and PDFF obtained from HISTO, HISTO-H, and ME-Dixon (r = 0.776, 0.811, 0.888, respectively; P < 0.001). ME-Dixon showed the best performance with moderate iron overload (AUC = 0.983). CONCLUSION: 3D ME-Dixon is useful for quantifying the LIC, especially with co-existing fatty liver. Its diagnostic performance is also superior to that of the HISTO sequence.

Thermo-sensitive self-assembly of poly(ethylene imine)/(phenylthio) acetic acid ion pair in surfactant solutions.

Poly(ethylene imine)/(phenylthio) acetic acid (PEI/PTA) ion pairs exhibited an upper critical solution temperature (UCST) behavior in an aqueous solution and the UCST was higher as the PTA content was more. The UCST of the ion pair decreased with increasing Brij S100 (BS 100, a nonionic surfactant) concentration but increased with increasing cetylpridinium chloride (CPC, a cationic surfactant) and sodium lauroylsarcosinate (SLS, an anionic surfactant) concentration. TEM microscopy demonstrated BS 100 markedly reduced the size of PEI/PTA ion pair self-assembly (IPSAM) whereas CPC and SLS had little effect on the size and the integrity of IPSAM. 1H NMR spectroscopy showed the hydrophobic interaction among the phenyl groups of PEI/PTA ion pairs took place. It also demonstrated the hydrophobic interaction between BS 100 and PTA and the electrostatic interaction between CPC and PTA and between SLS and PEI occurred. X-ray photoelectron spectroscopy disclosed the PTA of PEI/PTA IPSAM could be readily oxidized by H2O2 even at a low concentration (e.g. 0.005%). IPSAM released its payload (i.e. nile red) in a temperature and oxidation-responsive manner. The surfactants (i.e. BS 100, CPC, and SLS) suppressed the thermally triggered release in a different way. The effectiveness of the surfactant to suppress the release was in the order of BS 100 > CPC > SLS. IPSAM released its content more extensively as H2O2 (an oxidizing agent) concentration was higher. The ionic surfactants (i.e. CPS and SLS) had little effect on the oxidation-induced release degree but the nonionic surfactant (BS 100) markedly suppressed the release degree.

Intelligent Diagnosis and Analysis of Brain Lymphoma Based on DSC Imaging Features.

Currently, DSC has been extensively studied in the diagnosis, differential diagnosis, and prognosis evaluation of brain lymphoma, but it has not obtained a uniform standard. By combining DSC imaging features, this study investigated the imaging features and diagnostic value of several types of tumors such as primary brain lymphoma. At the same time, this study obtained data from brain lymphoma patients by data collection and set up different groups to conduct experimental studies to explore the correlation between IVIMMRI perfusion parameters and DSC perfusion parameters in brain lymphoma. Through experimental research, it can be seen that the combination of two perfusion imaging techniques can more fully reflect the blood flow properties of the lesion, which is beneficial to determine the nature of the lesion.

Liver iron quantification by 3 tesla MRI: calibration on a rabbit model.

PURPOSE: To determine the feasibility of liver iron quantification by 3 Tesla (T) MRI using a novel iron overload rabbit model. MATERIALS AND METHODS: Forty-two rabbits underwent iron dextran loading from 1 to 15 weeks. MRI signal intensity ratio (SIR) was measured using a gradient-echo sequence, and R2(1/T2) measured using an eight-echo spin-echo sequence at 3T. Ex vivo hepatic pathology was obtained for all rabbits studied. Postmortem assessments of liver iron concentration (LIC) were conducted in an atomic absorption spectrophotometer. MRI measures were fitted against LIC using linear regression for 30 of the iron-loaded rabbits. The remaining 12 iron-loaded rabbits were used to test the prediction accuracy of the derived models. RESULTS: LIC was linearly correlated to both liver-to-muscle SIR (r = -0.845) and R2 (r = 0.965) in a range achieved in this study (LIC < 10 mg/g dry tissue) at 3T. By regression, the linear equations were determined as: Y1 = 10.581-5.924X1 (Y1 : LIC, X1 :SIR); Y2 = -1.273+0.103X2 (Y2 :LIC, X2 :R2). In the 12 test rabbits, the predicted LICs using the derived equations agreed well with the results obtained using the spectrophotometer. CONCLUSION: Both SIR and R2 are highly correlated with LIC in a novel rabbit model. MRI quantification of liver iron overload is feasible at 3T.