Dynamic Contrast-Enhanced MRI in Abdominal Aortic Aneurysms as a Potential Marker for Disease Progression.

BACKGROUND: Abdominal aortic aneurysms (AAAs) may rupture before reaching maximum diameter (Dmax ) thresholds for repair. Aortic wall microvasculature has been associated with elastin content and rupture sites in specimens, but its relation to progression is unknown. PURPOSE: To investigate whether dynamic contrast-enhanced (DCE) MRI of AAA is associated with Dmax or growth. STUDY TYPE: Prospective. POPULATION: A total of 27 male patients with infrarenal AAA (mean age ± standard deviation = 75 ± 5 years) under surveillance with DCE MRI and 2 years of prior follow-up intervals with computed tomography (CT) or MRI. FIELD STRENGTH/SEQUENCE: A 3-T, dynamic three-dimensional (3D) fast gradient-echo stack-of-stars volumetric interpolated breath-hold examination (Star-VIBE). ASSESSMENT: Wall voxels were manually segmented in two consecutive slices at the level of Dmax . We measured slope to 1-minute and area under the curve (AUC) to 1 minute and 4 minutes of the signal intensity change postcontrast relative to that precontrast arrival, and, Ktrans , a measure of microvascular permeability, using the Patlak model. These were averaged over all wall voxels for association to Dmax and growth rate, and, over left/right and anterior/posterior quadrants for testing circumferential homogeneity. Dmax was measured orthogonal to the aortic centerline and growth rate was calculated by linear fit of Dmax measurements. STATISTICAL TESTS: Pearson correlation and linear mixed effects models. A P value <0.05 was considered statistically significant. RESULTS: In 44 DCE MRIs, mean Dmax was 45 ± 7 mm and growth rate in 1.5 ± 0.4 years of prior follow-up was 1.7 ± 1.2 mm per year. DCE measurements correlated with each other (Pearson r = 0.39-0.99) and significantly differed between anterior/posterior versus left/right quadrants. DCE measurements were not significantly associated with Dmax (P = 0.084, 0.289, 0.054 and 0.255 for slope, AUC at 1 minute and 4 minutes, and Ktrans , respectively). Slope and 4 minutes AUC significantly associated with growth rate after controlling for Dmax . CONCLUSION: Contrast uptake may be increased in lateral aspects of the AAA. Contrast enhancement 1-minute slope and 4-minutes AUC may be associated with a period of recent AAA growth that is independent of Dmax . EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

MR Elastography of Abdominal Aortic Aneurysms: Relationship to Aneurysm Events.

Background Abdominal aortic aneurysm (AAA) diameter remains the standard clinical parameter to predict growth and rupture. Studies suggest that using solely AAA diameter for risk stratification is insufficient. Purpose To evaluate the use of aortic MR elastography (MRE)-derived AAA stiffness and stiffness ratio at baseline to identify the potential for future aneurysm rupture or need for surgical repair. Materials and Methods Between August 2013 and March 2019, 72 participants with AAA and 56 healthy participants were enrolled in this prospective study. MRE examinations were performed to estimate AAA stiffness and the stiffness ratio between AAA and its adjacent remote normal aorta. Two Cox proportional hazards models were used to assess AAA stiffness and stiffness ratio for predicting aneurysmal events (subsequent repair, rupture, or diameter >5.0 cm). Log-rank tests were performed to determine a critical stiffness ratio suggesting high-risk AAAs. Baseline AAA stiffness and stiffness ratio were studied using Wilcoxon rank-sum tests between participants with and without aneurysmal events. Spearman correlation was used to investigate the relationship between stiffness and other potential imaging markers. Results Seventy-two participants with AAA (mean age, 71 years ± 9 [SD]; 56 men and 16 women) and 56 healthy participants (mean age, 42 years ± 16; 27 men and 29 women) were evaluated. In healthy participants, aortic stiffness positively correlated with age (ρ = 0.44; P < .001). AAA stiffness (event group [n = 21], 50.3 kPa ± 26.5 [SD]; no-event group [n = 21], 86.9 kPa ± 52.6; P = .01) and the stiffness ratio (event group, 0.7 ± 0.4; no-event group, 2.0 ± 1.4; P < .001) were lower in the event group than the no-event group at a mean follow-up of 449 days. AAA stiffness did not correlate with diameter in the event group (ρ = -0.06; P = .68) or the no-event group (ρ = -0.13; P = .32). AAA stiffness was inversely correlated with intraluminal thrombus area (ρ = -0.50; P = .01). Conclusion Lower abdominal aortic aneurysm stiffness and stiffness ratio measured with use of MR elastography was associated with aneurysmal events at a 15-month follow-up. © RSNA, 2022 See also the editorial by Sakuma in this issue.

Magnetic Resonance Elastography of Intervertebral Discs: Spin-Echo Echo-Planar Imaging Sequence Validation.

BACKGROUND: Magnetic resonance elastography (MRE) is an imaging technique that can noninvasively assess the shear properties of the intervertebral disc (IVD). Unlike the standard gradient recalled echo (GRE) MRE technique, a spin-echo echo-planar imaging (SE-EPI) sequence has the potential to improve imaging efficiency and patient compliance. PURPOSE: To validate the use of an SE-EPI sequence for MRE of the IVD compared against the standard GRE sequence. STUDY TYPE: Cross-over. SUBJECTS: Twenty-eight healthy volunteers (15 males and 13 females, age range: 19-55). FIELD STRENGTH/SEQUENCE: 3 T; GRE, SE-EPI with breath holds (SE-EPI-BH) and SE-EPI with free breathing (SE-EPI-FB) MRE sequences. ASSESSMENT: MRE-derived shear stiffnesses were calculated via principal frequency analysis. SE-EPI derived shear stiffness and octahedral shear strain signal-to-noise ratios (OSS-SNR) were compared against those derived using the GRE sequence. The reproducibility and repeatability of SE-EPI stiffness measurements were determined. Shear stiffness was evaluated in the nucleus pulposus (NP) and annulus fibrosus (AF) regions of the disc. Scan times between sequences were compared. STATISTICAL TESTS: Linear mixed models, Bland-Altman plots, and Lin's concordance correlation coefficients (CCCs) were used with P < 0.05 considered statistically significant. RESULTS: Good correlation was observed between shear stiffnesses derived from the SE-EPI sequences with those derived from the GRE sequence with CCC values greater than 0.73 and 0.78 for the NP and AF regions, respectively. OSS-SNR was not significantly different between GRE and SE-EPI sequences (P > 0.05). SE-EPI sequences generated highly reproducible and repeatable stiffness measurements with CCC values greater than 0.97 in the NP and AF regions and reduced scan time by at least 51% compared to GRE. SE-EPI-BH and SE-EPI-FB stiffness measurements were similar with CCC values greater than 0.98 for both regions. DATA CONCLUSION: SE-EPI-based MRE-derived stiffnesses were highly reproducible and repeatable and correlated with current standard GRE MRE-derived stiffness estimates while reducing scan times. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Magnetic resonance elastography for estimating in vivo stiffness of the abdominal aorta using cardiac-gated spin-echo echo-planar imaging: a feasibility study.

INTRODUCTION: Magnetic resonance elastography (MRE)-derived aortic stiffness is a potential biomarker for multiple cardiovascular diseases. Currently, gradient-recalled echo (GRE) MRE is a widely accepted technique to estimate aortic stiffness. However, multi-slice GRE MRE requires multiple breath-holds (BHs), which can be challenging for patients who cannot consistently hold their breath. The aim of this study was to investigate the feasibility of a multi-slice spin-echo echo-planar imaging (SE-EPI) MRE sequence for quantifying in vivo aortic stiffness using a free-breathing (FB) protocol and a single-BH protocol. METHOD: On Scanner 1, 25 healthy subjects participated in the validation of FB SE-EPI against FB GRE. On Scanner 2, another 15 healthy subjects were recruited to compare FB SE-EPI with single-BH SE-EPI. Among all volunteers, five participants were studied on both scanners to investigate the inter-scanner reproducibility of FB SE-EPI aortic MRE. Bland-Altman analysis, Lin's concordance correlation coefficient (LCCC) and coefficient of variation (COV) were evaluated. The phase-difference signal-to-noise ratios (PD SNR) were compared. RESULTS: Aortic MRE using FB SE-EPI and FB GRE yielded similar stiffnesses (paired t-test, P = 0.19), with LCCC = 0.97. The FB SE-EPI measurements were reproducible (intra-scanner LCCC = 0.96) and highly repeatable (LCCC = 0.99). The FB SE-EPI MRE was also reproducible across different scanners (inter-scanner LCCC = 0.96). Single-BH SE-EPI scans yielded similar stiffness to FB SE-EPI scans (LCCC = 0.99) and demonstrated a low COV of 2.67% across five repeated measurements. CONCLUSION: Multi-slice SE-EPI aortic MRE using an FB protocol or a single-BH protocol is reproducible and repeatable with advantage over multi-slice FB GRE in reducing acquisition time. Additionally, FB SE-EPI MRE provides a potential alternative to BH scans for patients who have challenges in holding their breath.

Magnetic resonance elastography-derived stiffness of the kidneys and its correlation with water perfusion.

Stiffness plays an important role in diagnosing renal fibrosis. However, kidney stiffness is altered by perfusion changes in many kidney diseases. Therefore, the aim of the current study is to determine the correlation of kidney stiffness with water intake. We hypothesize that kidney stiffness will increase with 1 L of water intake due to increased water perfusion to the kidneys. Additionally, stiffness of the kidneys will correlate with apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values before and after water intake. A 3 T MRI scanner was used to perform magnetic resonance elastography and diffusion tensor imaging of the kidneys on 24 healthy subjects (age range: 22-66 years) before and after water intake of 1 L. A 3D T1-weighted bladder scan was also performed to measure bladder volume before and after water intake. A paired t-test was performed to evaluate the effect of water intake on the stiffness of kidneys, in addition to bladder volume. A Spearman correlation test was performed to determine the association between stiffness, bladder volume, ADC and FA values of both kidneys before and after water intake. The results show a significant increase in stiffness in different regions of the kidney (ie, percentage increase ranged from 3.6% to 7.5%) and bladder volume after water intake (all P < 0.05). A moderate significant negative correlation was observed between change in kidney stiffness and bladder volume (concordance correlation coefficient = -0.468, P < 0.05). No significant correlation was observed between stiffness and ADC or FA values before and after water intake in both kidneys (P > 0.05). Water intake caused a significant increase in the stiffness of the kidneys. The negative correlation between the change in kidney stiffness and bladder volume, before and after water intake, indicates higher perfusion pressure in the kidneys, leading to increased stiffness.

Magnetic resonance elastography of the lungs: A repeatability and reproducibility study.

Lung diseases are one of the leading causes of death worldwide, from which four million people die annually. Lung diseases are associated with changes in the mechanical properties of the lungs. Several studies have shown the feasibility of using magnetic resonance elastography (MRE) to quantify the lungs' shear stiffness. The aim of this study is to investigate the reproducibility and repeatability of lung MRE, and its shear stiffness measurements, obtained using a modified spin echo-echo planar imaging (SE-EPI) MRE sequence. In this study, 21 healthy volunteers were scanned twice by repositioning the volunteers to image right lung both at residual volume (RV) and total lung capacity (TLC) to assess the reproducibility of lung shear stiffness measurements. Additionally, 19 out of the 21 volunteers were scanned immediately without moving the volunteers to test the repeatability of the modified SE-EPI MRE sequence. A paired t-test was performed to determine the significant difference between stiffness measurements obtained at RV and TLC. Concordance correlation and Bland-Altman's analysis were performed to determine the reproducibility and repeatability of the SE-EPI MRE-derived shear stiffness measurements. The SE-EPI MRE sequence is highly repeatable with a concordance correlation coefficient (CCC) of 0.95 at RV and 0.96 at TLC. Similarly, the stiffness measurements obtained across all volunteers were highly reproducible with a CCC of 0.95 at RV and 0.92 at TLC. The mean shear stiffness of the lung at RV was 0.93 ± 0.22 kPa and at TLC was 1.41 ± 0.41 kPa. TLC showed a significantly higher mean shear stiffness (P = 0.0004) compared with RV. Lung MRE stiffness measurements obtained using the SE-EPI sequence were reproducible and repeatable, both at RV and TLC. Lung shear stiffness changes across respiratory cycle with significantly higher stiffness at TLC than RV.

Magnetic Resonance Elastography of kidneys: SE-EPI MRE reproducibility and its comparison to GRE MRE.

The purpose of this study is 1) to demonstrate reproducibility of spin echo-echo planar imaging (SE-EPI) magnetic resonance elastography (MRE) to estimate kidney stiffness; and 2) to compare SE-EPI MRE and gradient recalled echo (GRE) MRE-derived stiffness estimations in various anatomical regions of the kidney. Kidney MRE was performed on 33 healthy subjects (8 for SE-EPI MRE reproducibility and 25 for comparison with GRE MRE; age range: 22-66 years) in a 3 T MRI scanner. To demonstrate SE-EPI MRE reproducibility, subjects were scanned for the first scan and then asked to leave the scan room and repositioned again for the second (repeat) scan. Similar set-up was used for GRE MRE as well. The displacement data was then processed to obtain overall stiffness estimates of the kidney. Concordance correlation analyses were performed to determine SE-EPI MRE reproducibility and agreement between GRE MRE and SE-EPI MRE derived stiffness. A high concordance correlation (ρc  = 0.95; p-value<0.0001) was obtained for SE-EPI MRE reproducibility. Good concordance correlation was observed (ρc  = 0.84; p < 0.0001 for both kidneys, ρc  = 0.91; p < 0.0001 for right kidney and ρc  = 0.78; p < 0.0001 for left kidney) between GRE MRE and SE-EPI MRE derived stiffness measurements. Paired t-test results showed that stiffness value of medulla was significantly (p < 0.0001) greater than cortex using SE-EPI MRE as well as GRE MRE. SE-EPI MRE was reproducible and good agreement was observed in MRE-derived stiffness measurements obtained using SE-EPI and GRE sequences. Therefore, SE-EPI can be used for kidney MRE applications.

LncRNA-MALAT1 Promotes Angiogenesis of Thyroid Cancer by Modulating Tumor-Associated Macrophage FGF2 Protein Secretion.

Tumor-associated macrophages (TAMs) in the tumor microenvironment have been associated with enhanced tumor progression. In this study, we investigated the role and molecular mechanisms of MALAT1 in TAMs derived from thyroid cancer. The expression of MALAT1 and FGF2 in thyroid cancer tissues and cells were measured by quantitative real-time PCR and Western blot. TAMs were transfected with indicated constructs. Then the culture medium (CM) from TAMs was harvested for assay. Secreted FGF2 protein levels and TNF-α, IL-12, and IL-10 levels were detected by ELISA. The cell proliferation, migration, and invasion of FTC133 cells were determined with a CCK-8 assay and a Transwell assay, respectively. In addition, HUVEC vasculature formation was measured by matrigel angiogenesis assay. The higher levels of MALAT-1 and FGF2 were observed in thyroid cancer tissues and in thyroid cancer cells compared to that in the control. Besides, in the presence of si-MALAT1, the levels of TNF-α and IL-12 were significantly up-regulated whereas IL-10 was down-regulated in the CM from TAMs. Moreover, down-regulation of MALAT1 in TAMs reduced proliferation, migration, and invasion of FTC133 cells and inhibited angiogenesis. However, overexpression of FGF2 blocked the effects of MALAT1 siRNAs on cell migration, invasion, and angiogenesis. Our results suggest that MALAT1-mediated FGF2 protein secretion from TAMs inhibits inflammatory cytokines release, promotes proliferation, migration, and invasion of FTC133 cells and induces vasculature formation. J. Cell. Biochem. 118: 4821-4830, 2017. © 2017 Wiley Periodicals, Inc.

In vivo quantification of aortic stiffness using MR elastography in hypertensive porcine model.

PURPOSE: Aortic stiffness plays an important role in evaluating and predicting the progression of systemic arterial hypertension (SAH). The aim of this study is to determine the stiffness of aortic wall using MR elastography (MRE) in a hypertensive porcine model and compare it against invasive aortic pressure measurements. METHODS: Renal wrapping surgery was performed on eight pigs to induce SAH. Aortic MRE was performed at baseline and 2 months postsurgery using a retrospectively pulse-gated gradient-echo MRE sequence on a 1.5 tesla scanner. Mechanical waves of 70 Hz were introduced into the aorta. Invasive central aortic pressure measurements were obtained prior to each scan to calculate mean arterial pressure (MAP). MRE data were analyzed to obtain effective aortic stiffness. Spearman's rank correlation analysis was performed to assess the relationship between MAP and MRE-derived aortic stiffness. RESULTS: Significant increase in effective aortic stiffness was observed between baseline and 2 months postsurgery measurements (paired t test; P = 0.004). The average MAP, determined by pooling all animals, was 65.24 ± 9.42 mm Hg at baseline and 92.57 ± 11.80 mm Hg 2 months postsurgery with P < 0.0001. Moderate linear correlation was observed between MAP and effective aortic stiffness (ρ = 0.52; P = 0.046). CONCLUSION: This study demonstrated that, in a SAH porcine model, MRE-derived aortic stiffness increased with increase in MAP. Magn Reson Med 78:2315-2321, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Magnetic Relaxation Dynamics of a Centrosymmetric Dy2 Single-Molecule Magnet Triggered by Magnetic-Site Dilution and External Magnetic Field.

A centrosymmetric Dy2 single-molecule magnet (SMM) and its doped diamagnetic yttrium analogues, Dy0.19Y1.81 and Dy0.10Y1.90, were solvothermally synthesized to investigate the effects of intramolecular exchange coupling and quantum tunneling of magnetization (QTM) on the magnetic relaxation dynamics. Constructed from two hula-hoop-like DyIII ions and a pair of phenoxido groups, the antiferromagnetically coupled Dy2 exhibits a thermal-activated zero-field effective energy barrier (Ueff) of 277.7 K and negligible hysteresis loop at 2.0 K. The doping of a diamagnetic YIII matrix with 90.5% and 95.0% molar ratios reveals the single-ion origin of the Orbach channel, increases the relaxation time by partially quenching the QTM process, and induces an open hysteresis loop until 5.0 K. In contrast, an optimal dc field of 1.0 kOe improves the barrier height up to 290.1 K through complete elimination of the QTM and delays the relaxation time of the direct relaxation pathway. More interestingly, the collaborative dual effects of magnetic-site dilution and external magnetic field make the effective energy barrier and relaxation time increase 8.1% and 49 times, respectively. Thus, the overall magnetization dynamics of the Dy2 system systematically elaborate the inherent interplay of the QTM and Orbach processes on the effective energy barrier, highlighting the vital role of the relaxation time on the coercive hysteresis loop.

MicroRNA-544 down-regulates both Bcl6 and Stat3 to inhibit tumor growth of human triple negative breast cancer.

Triple negative breast cancer lacking estrogen receptor (ER), progesterone receptor and Her2 account for account for the majority of the breast cancer deaths, due to the lack of specific gene targeted therapy. Our current study aimed to investigate the role of miR-544 in triple negative breast cancer. Endogenous levels of miR-544 were significantly lower in breast cancer cell lines than in human breast non-tumorigenic and mammary epithelial cell lines. We found that miR-544 directly targeted the 3'-untranslated region (UTR) on both Bcl6 and Stat3 mRNAs, and overexpression of miR-544 in triple negative breast cancer cells significantly down-regulated expressions of Bcl6 and Stat3, which in turn severely inhibited cancer cell proliferation, migration and invasion in vitro. Employing a mouse xenograft model to examine the in vivo function of miR-544, we found that expression of miR-544 significantly repressed the growth of xenograft tumors. Our current study reported miR-544 as a tumor-suppressor microRNA particularly in triple negative breast cancer. Our data supported the role of miR-544 as a potential biomarker in developing gene targeted therapies in the clinical treatment of triple negative breast cancer.

[Expressions of MACC1, Snail, and KISS-1 Proteins in Infiltrating Breast Carcinoma and Its Clinicopathological Features].

OBJECTIVES: To investigate the protein expressions of metastasis-associated in colon cancer 1 (MACC1), KISS-1 (a cancer ruppressor gene) and Snail (the marker of epithelial-mesenchymal transition) in infiltrating breast carcinoma (IBC) and explore the role of them in invasion, metastasis and prognosis in IBC. METHODS: Expressions of MACC1, Snail and KISS-1 were examined by immunohistochemistry in 250 specimens of IBC and 80 specimens of normal breast tissues. Their clinicopathological features were analyzed, and their influence on patients' survival was identified. RESULTS: The positive rate of MACC1, Snail and KISS-1 in normal breast tissues and IBC tissues was 7.5%, 5.0%, 87.5% and 63.6%, 58.8%, 38.0%, respectively. And there was a significant difference between the IBC group and control group ( P<0.05). The positive expressions of MACC1, Snail and KISS-1 were significantly different in different TNM stages, lymph node metastasis, types and grades of tumor ( P<0.05). The survival time of positive KISS-1 group was significantly longer than that of negative group ( P<0.001); the survival time was significantly shorter in positive MACC1 group or Snail group than that of negative groups (both P<0.001). Cox regression analysis indicated that the positive expressions of MACC1, Snail and negative expression of KISS-1 were independent risk factors of IBC (P<0.05). CONCLUSIONS: Abnormal expression of MACC1, Snail and KISS-1 should be involved in the invasion and metastasis of IBC. The combined detection in the expressions of MACC1, Snail and KISS-1 at the early stage may play an important role in predicting the progression and prognosis of IBC.

Clinicopathological significance of cancer stem cells marked by CD133 and KAI1/CD82 expression in laryngeal squamous cell carcinoma.

BACKGROUND: Presently, CD133 is one of the hottest markers to characterize cancer stem cells and KAI1/CD82 is reported as an important marker for the metastasis and prognosis of many cancers. The purpose of our study is to explore the relationship between cancer stem cells (CSCs) marked by CD133 and KAI1/CD82 expression and the clinicopathological characteristics of patients with laryngeal squamous cell carcinoma (LSCC). METHODS: Immunohistochemical analysis was used to detect the expression of CD133 and KAI1/CD82 in 83 archival surgical specimens of human LSCC and 83 cases of normal laryngeal tissues. RESULTS: In LSCC, positive rates of 49.4% and 41.0% were obtained for CD133 and KAI1/CD82, respectively. The expression of CD133 in LSCC tissues was significantly higher than that in normal tissues (P<0.001), and the expression of CD133 was positively associated with pTNM stage (P=0.005), pathological grade (P=0.001), and lymph node metastasis (P<0.001). The reduced expression of KAI1/CD82 was present in LSCC tissues. The positive rate of KAI1/CD82 expression was negatively correlated with pTNM stage (P=0.014), pathological grade (P<0.001), and lymph node metastasis (P=0.007). A correlation analysis showed that there was a negative relationship between the expression of CD133 and KAI1/CD82 protein in LSCC tissues (P<0.001). By Kaplan-Meier analysis, the expression of CD133 was negatively correlated with overall survival (OS) (log-rank=40.949, P<0.001) and disease-free survival (DFS) (log-rank=39.307, P<0.001) time of LSCC. The expression of KAI1/CD82 was positively correlated with OS (log-rank=40.279, P<0.001) and DFS (log-rank=39.271, P<0.001) time of LSCC. Cox regression analysis: the expression of CD133 and KAI1/CD82, and pTNM stages were independent prognostic factors of LSCC (P<0.05). CONCLUSIONS: Thus the detection of CD133 and KAI1/CD82 proteins may be used as a potential indicator of LSCC prognosis.

TYMS Knockdown Suppresses Cells Proliferation, Promotes Ferroptosis via Inhibits PI3K/Akt/mTOR Signaling Pathway Activation in Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is characterized by a grim prognosis and numerous challenges. The objective of our study was to examine the role of thymidylate synthase (TYMS) in TNBC and its impact on ferroptosis. The expression of TYMS was analyzed in databases, along with its prognostic correlation. TYMS positive expression was identified through immunohistochemistry (IHC), while real-time quantitative PCR (qRTPCR) was employed to measure TYMS mRNA levels in various cell lines. Western blotting was utilized to assess protein expression. Cell proliferation, mobility, apoptosis, and reactive oxygen species (ROS) levels were evaluated using CCK8, wound scratch healing assay, transwell assay, and flow cytometry, respectively. Additionally, a tumor xenograft model was established in BALB/c nude mice for further investigation. Tumor volume and weight were measured, and histopathological analysis using hematoxylin and eosin (H&E) staining was conducted to assess tumor tissue changes. IHC staining was employed to detect the expression of Ki67 in tumor tissues. High expression of TYMS was observed in TNBC and was found to be correlated with poor prognosis in patients. Among various cell lines, TYMS expression was highest in BT549 cells. Knockdown of TYMS resulted in suppression of cell proliferation and mobility, as well as promotion of apoptosis. Furthermore, knockdown of TYMS led to increased accumulation of ROS and Fe2+ levels, along with upregulation of ACLS4 expression and downregulation of glutathione peroxidase 4 (GPX4) expression. In vivo studies showed that knockdown of TYMS inhibited tumor growth. Additionally, knockdown of TYMS was associated with inhibition of mTOR, p-PI3K, and p-Akt expression. Our research showed that the knockdown of TYMS suppressed the TNBC progression by inhibited cells proliferation via ferroptosis. Its underlying mechanism is related to the PI3K /Akt pathway. Our study provides a novel sight for the suppression effect of TYMS on TNBC.

Interlayer interaction-force-tuned magnetic responses in CoII-tetrazolate-carboxylate system from canted antiferromagnet to field-induced metamagnet.

Interlayer magnetic couplings of low-dimensional magnets have significantly dominated magnetic behavior through skillful regulation of interlayer interacting forces. To identify interaction-force-regulated interlayer magnetic communications, two air-stable Co(II)-based coordination polymers (CPs), a well-isolated layered structure with approximately 12.6 Å interlayer separation and a carboxylate-extended three-dimensional framework with an inter-ribbon distance of 5.8 Å, have been solvothermally fabricated by varying polycarboxylate mediators in a ternary CoII-tetrazolate-carboxylate system. The layered CP with antiparallel-arranged {Co2(COO)2}n chains interconnected only via cyclic tetrazolyl linkages behaves as a spin-canted antiferromagnet with a Néel temperature of 2.6 K, due to strong intralayer antiferromagnetic couplings and negligible interlayer magnetic interactions. In contrast, the compact three-dimensional framework with corner-sharing Δ-ribbons tightly aggregated through µ2-η1:η1-COO- is a field-induced metamagnet from a canted antiferromagnet to a weak ferromagnet with a small critical field of Hc = 90 Oe. Apparently, these interesting magnetic responses reveal the importance of an interacting force from the magnetic subunits for the magnetic behavior of the molecular magnet, greatly enriching the magnetostructural correlations of transition-metal-based molecular magnets.

Measurement of Abdominal Aortic Aneurysm Strain Using MR Deformable Image Registration: Accuracy and Relationship to Recent Aneurysm Progression.

BACKGROUND: Management of asymptomatic abdominal aortic aneurysm (AAA) based on maximum aneurysm diameter and growth rate fails to preempt many ruptures. Assessment of aortic wall biomechanical properties may improve assessment of progression and rupture risk. This study aimed to assess the accuracy of AAA wall strain measured by cine magnetic resonance imaging (MRI) deformable image registration (MR strain) and investigate its relationship with recent AAA progression. METHODS: The MR strain accuracy was evaluated in silico against ground truth strain in 54 synthetic MRIs generated from a finite element model simulation of an AAA patient's abdomen for different aortic pulse pressures, tissue motions, signal intensity variations, and image noise. Evaluation included bias with 95% confidence interval (CI) and correlation analysis. Association of MR strain with AAA growth rate was assessed in 25 consecutive patients with >6 months of prior surveillance, for whom cine balanced steady-state free-precession imaging was acquired at the level of the AAA as well as the proximal, normal-caliber aorta. Univariate and multivariate regressions were used to associate growth rate with clinical variables, maximum AAA diameter (Dmax), and peak circumferential MR strain through the cardiac cycle. The MR strain interoperator variability was assessed using bias with 95% CI, intraclass correlation coefficient, and coefficient of variation. RESULTS: In silico experiments revealed an MR strain bias of 0.48% ± 0.42% and a slope of correlation to ground truth strain of 0.963. In vivo, AAA MR strain (1.2% ± 0.6%) was highly reproducible (bias ± 95% CI, 0.03% ± 0.31%; intraclass correlation coefficient, 97.8%; coefficient of variation, 7.14%) and was lower than in the nonaneurysmal aorta (2.4% ± 1.7%). Dmax (ß = 0.087) and MR strain (ß= -1.563) were both associated with AAA growth rate. The MR strain remained an independent factor associated with growth rate (ß= -0.904) after controlling for Dmax. CONCLUSIONS: Deformable image registration analysis can accurately measure the circumferential strain of the AAA wall from standard cine MRI and may offer patient-specific insight regarding AAA progression.

Stabilizer-induced different in vivo behaviors for intramuscularly long-acting celecoxib nanocrystals.

Nanocrystals (NCs) have been widely recognized as an available policy for the formulation of long-acting injections for insoluble drugs. Stabilizers are extremely important for the physical stability of NCs because they can reduce the surface free energy of the system. However, whether stabilizers can affect the in vivo performances of long-acting injectable NCs is unclear. In this study, three celecoxib (CXB) NCs formulated with different stabilizers (PVP K17, TPGS, and F68) were successfully developed by the wet milling method. Among the formulations, CXB-NCs/PVP K17 had a lower dissolution rate. More importantly, CXB-NCs/PVP K17 did not show burst release after intramuscular (i.m.) injection to rats, and it had a strong analgesic effect. These results showed that the stabilizers played a key role in the in vivo behaviors of long-acting injectable NCs. This strongly suggested that the burst release could be avoided by alteration of stabilizers of NCs by i.m. injection.

Slow relaxation of Dy(III) single-ion magnets dominated by the simultaneous binding of chelating ligands in low-symmetry ligand-fields.

Electronic effect and geometry distortion of low-symmetry ligand-field on the anisotropy barrier (Ueff) of spin reversal have been compared in three Dy(III) single-ion magnets through the simultaneous binding of chelating ligands. The substitution of N,O-salicylaldoxime by N,N'-1,10-phenanthroline in the distorted triangular-dodecahedronal field sharply decreases the Ueff by 286 K due to an increase in non-preferred transverse anisotropy, while the geometry distortion with CShM = 1.569 went down to 1.376 only lowering the Ueff by 12 K. The co-coordination strategy of heterodonor ligands highlights the importance of ligand-surroundings on the relaxation dynamics.

Roles of effective stabilizers in improving oral bioavailability of naringenin nanocrystals: Maintenance of supersaturation generated upon dissolution by inhibition of drug dimerization.

Nanocrystals (NCs), a colloidal dispersion system formulated with stabilizers, have attracted widespread interest due to their ability to effectively improve the oral bioavailability of poorly water-soluble drugs. The stabilizer plays a key role because it can affect the physical stability and even the oral bioavailability of NCs. However, how stabilizers affect the bioavailability of NCs remains unknown. In this study, F68, F127, HPMC, and PVP were each used as a stabilizer to formulate naringenin NCs. The NCs formulated with PVP exhibited excellent release behaviors, cellular uptake, permeability, oral bioavailability, and anti-inflammatory effects. The underlying mechanism is that PVP effectively inhibits the formation of naringenin dimer, which in turn improves the physical stability of the supersaturated solution generated when NC is dissolved. This finding provides insights into the effects of stabilizers on the in vivo performances of NCs and supplies valuable knowledge for the development of poorly water-soluble drugs.