Search

Thrombolysis is a standard treatment for rapidly restoring blood flow. However, the application of urokinase-type plasminogen activator (Uk) in clinical therapy is limited due to its nonspecific distribution and inadequate therapeutic accumulation. Precise thrombus imaging and site-specific drug delivery can enhance the diagnostic and therapeutic efficacy for thrombosis. Accordingly, we developed a P-selectin-specific, photothermal theranostic nanocomposite for thrombus-targeted codelivery of Uk and indocyanine green (ICG, a contrast agent for near-infrared (NIR) fluorescence imaging). We evaluated its capabilities for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. Mesoporous silica-coated gold nanorods (Si-AuNRs) were functionalized with an arginine-rich peptide to create an organic template for the adsorption of ICG and fucoidan (Fu), an algae-derived anticoagulant. Uk was loaded into the SiO2 pores of the Si-AuNRs through the formation of a Fu-Uk-ICG complex on the peptide-functionalized template. The Fu-Uk/ICG@SiAu NRs nanocomposite increased the photostability of ICG and improved its targeting/accumulation at blood clot sites with a strong NIR fluorescence intensity for precise thrombus imaging. Furthermore, ICG incorporated into the nanocomposite enhanced the photothermal effect of Si-AuNRs. Fu, as a P-selectin-targeting ligand, enabled the nanocomposite to target a thrombus site where platelets were activated. The nanocomposite enabled a faster release of Uk for rapid clearing of blood clots and a slower release of Fu for longer lasting prevention of thrombosis regeneration. The nanocomposite with multiple functions, including thrombus-targeting drug delivery, photothermal thrombolysis, and NIR fluorescence imaging, is thus an advanced theranostic platform for thrombolytic therapy with reduced hemorrhaging risk and enhanced imaging/thrombolysis efficiency. Statement of significance Herein, for the first time, a P-selectin specific, photothermal theranostic nanocomposite for thrombus-targeted co-delivery of urokinase and NIR fluorescence contrast agent indocyanine green (ICG) was developed. We evaluated the potential of this theranostic nanocomposite for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. The nanocomposite showed multiple functions including thrombus targeting and imaging, and photothermal thrombolysis. Besides, it allowed faster release of the thrombolytic urokinase for rapidly clearing blood clots and slower release of a brown algae-derived anticoagulant fucoidan (also acting as a P-selectin ligand) for prevention of thrombosis regeneration. The nanocomposite is thus a new and advanced theranostic platform for targeted thrombolytic therapy.

Nuclear factor (NF)-κB signaling in cancer cells has been reported to be involved in tumorigenesis. Phosphorylation and degradation of inhibitor of NF-κBα (IκBα) is a canonical pathway of NF-κB signaling. Here, we aimed to identify and characterize noncanonical activation of NF-κB signaling by ubiquitin-conjugating enzyme E2S (UBE2S) in lung adenocarcinoma cells. TCGA and the Human Atlas Protein Database were used to analyze the survival rate of lung adenocarcinoma patients in conjunction with UBE2S expression. In addition, PC9, H460, H441 and A549 lung adenocarcinoma cells were used in this study. PC9 and H460 cells were selected for further analysis because they expressed different UBE2S protein levels. Specific IKK inhibitors, PS1145 and SC514, were used to assess IκBα phosphorylation. Western blot analysis was used to assess protein levels in PC9 and H460 cells. A scratch wound-healing assay was used to analyze the migrative abilities of PC9 and H460 cells. Overexpression and knockdown of UBE2S in H460 and PC9 cells were used to analyze their effects on downstream protein levels. Immunoprecipitation, immunofluorescent staining, glutathione S transferase (GST) pull-down and in vitro binding assays were used to analyze the interaction between UBE2S and IκBα. A luciferase assay was used to analyze activation of NF-κB signaling regulated by UBE2S. An in vivo zebrafish xenograft model was used to assess metastasis of PC9 cells regulated by UBE2S. We found that UBE2S expression in lung adenocarcinoma patients was negatively related to survival rate. The protein level of UBE2S was higher in PC9 cells than in H460 cells, which was opposite to that observed for IκBα. PC9 cells showed a higher UBE2S expression and migrative ability than H460 cells. Phosphorylation of IκBα was not changed by treatment with the IKK-specific inhibitors PS1145 and SC514 in PC9 and H460 cells. Overexpression and knockdown of UBE2S in H460 and PC9 cells revealed that the protein levels of IκBα were inversely regulated. Immunoprecipitation, immunofluorescent staining, GST pull-down and in vitro binding assays revealed direct binding of UBE2S with IκBα. Nuclear P65 protein levels and luciferase assays showed that NF-κB signaling was regulated by UBE2S. The expression of epithelial-to-mesenchymal (EMT) markers and the migrative ability of lung adenocarcinoma cells were also regulated by UBE2S. A zebrafish xenograft tumor model showed a reduction in the metastasis of PC9 cells that was induced by UBE2S knockdown. Higher UBE2S expression in lung adenocarcinomas may lead to increased binding with IκBα to activate NF-κB signaling and promote adenocarcinoma cell metastasis. UBE2S may serve as a potential therapeutic target for lung adenocarcinomas.

Tolvaptan has been approved for the treatment of autosomal dominant polycystic kidney disease and heart failure. However, the role of tolvaptan in patients with abdominal aortic aneurysm (AAA) has not been examined. Human aortic smooth muscle cells (HASMCs) were used as the in vitro model. Via Ang II infusion, experimental AAAs were induced in Apo-E knockout mice. In vitro study showed that tolvaptan suppressed matrix metalloproteinase (MMP) expressions (MMP-2 and MMP-9) and apoptosis in Ang II-stimulated HASMCs. In the Apo-E knockout mice with Ang II-induced AAA, the animals exhibited AAA formation with elastic lamina degradation, dilatation of the suprarenal aorta, increased macrophage infiltration and higher expressions of MMPs. Treatment with a high dose of tolvaptan prevented experimental AAA formation while preserving the elastic lamina structure, reducing inflammatory macrophages, and inhibiting gelatinolytic activity, MMP expressions and apoptosis of SMCs in aorta tissue. Specifically, tolvaptan reduced the expression of receptor-interacting protein kinase 3 (RIP3) and decreased apoptosis of SMCs. Our data demonstrated that tolvaptan reduces experimental AAA formation and dissection by inhibiting destruction of the aortic structure integrity and reducing inflammatory macrophage infiltration, MMP-2 and MMP-9 expressions, and apoptosis of vascular SMCs, indicating tolvaptan may have therapeutic potential for AAA and dissection.

Precise risk stratification in lymphadenectomy is important for patients with endometrial cancer (EC), to balance the therapeutic benefit against the operation-related morbidity and mortality. We aimed to investigate added values of computer-aided segmentation and machine learning based on clinical parameters and diffusion-weighted imaging radiomics for predicting lymph node (LN) metastasis in EC. This prospective observational study included 236 women with EC (mean age ± standard deviation, 51.2 ± 11.6 years) who underwent magnetic resonance (MR) imaging before surgery during July 2010–July 2018, randomly split into training (n = 165) and test sets (n = 71). A decision-tree model was constructed based on mean apparent diffusion coefficient (ADC) value of the tumor (cutoff, 1.1 × 10−3 mm2/s), skewness of the relative ADC value (cutoff, 1.2), short-axis diameter of LN (cutoff, 1.7 mm) and skewness ADC value of the LN (cutoff, 7.2 × 10−2), as well as tumor grade (1 vs. 2 and 3), and clinical tumor size (cutoff, 20 mm). The sensitivity and specificity of the model were 94% and 80% for the training set and 86%, 78% for the independent testing set, respectively. The areas under the receiver operating characteristics curve (AUCs) of the decision-tree was 0.85—significantly higher than the mean ADC model (AUC = 0.54) and LN short-axis diameter criteria (AUC = 0.62) (both p &lt, 0.0001). We concluded that a combination of clinical and MR radiomics generates a prediction model for LN metastasis in EC, with diagnostic performance surpassing the conventional ADC and size criteria.

OBJECTIVES Although commercial iliac branch devices offer a new and valid endovascular approach to treating iliac aneurysm and effectively preserve antegrade flow of the internal iliac artery, their use may not be suited for all types of challenging anatomy, especially isolated common iliac artery aneurysm. Our custom-made iliac bifurcation device has a unique design and excludes both combined and isolated iliac branch aneurysm. This study validated the efficacy and safety of the custom device by comparing clinical outcomes between groups receiving commercial and custom devices. METHODS Data of consecutive patients receiving iliac bifurcation device implantation for iliac aneurysm with or without concomitant endovascular repair for abdominal aortic aneurysm from January 2010 to May 2019 were reviewed. RESULTS Iliac bifurcation device implantation with or without concomitant abdominal aortic aneurysm stent grafting was completed in 46 patients (commercial, n = 35; custom, n = 11). No significant differences were observed regarding postoperative complications, occlusion or endoleak. Comparisons of primary (80.8% vs 85.7%, P = 0.88) and secondary (86.5% vs 85.7%, P = 0.85) patency and freedom from reintervention (88.2% vs 100%, P = 0.33), all-cause mortality (78.6% vs 100%, P = 0.25) and aneurysm-related mortality (100% vs 100%, P = 1.00) also indicated no differences at a 5-year surveillance point. Furthermore, the iliac aneurysms of the groups displayed similar shrinkage 1 year after procedures. CONCLUSIONS For iliac aneurysm, the novel custom-made iliac bifurcation device is an adaptable design not inferior to commercial devices with regard to postoperative complications, bridge occlusion, endoleak and short-term aneurysm remodelling. It provides an alternative for treatment, particularly when certain anatomic challenges are present. Clinical trial registration 2018-07-050BC, 2017-01-023ACF.

Background A triage test to assist clinical decision-making on choosing primary chemoradiation for cervical carcinomas or primary surgery for endometrial carcinomas is important. Purpose or Hypothesis To develop and validate a multiparametric prediction model based on MR imaging and spectroscopy in distinguishing adenocarcinomas of uterine cervical or endometrial origin. Study Type Prospective diagnostic accuracy study. Population Eighty-seven women: 25 cervical and 62 endometrial adenocarcinomas divided into training (n = 43; cervical/endometrial adenocarcinomas = 11/32) and validation (n = 44; 14/30) datasets. Field Strength/Sequence The 3T diffusion-weighted (DW) MR imaging and MR spectroscopy. Assessment Morphology, volumetric DW MR imaging and spectroscopy (MDS) scoring system with total points 0–5, based on presence of the following MR features assessed independently by two radiologists: (a) epicenter at the cervix, (b) rim enhancement, (c) disrupted cervical stromal integrity, (d) mean volumetric apparent diffusion coefficient values (ADCmean) higher than 0.98 × 10-3 mm2/s, (e) fatty acyl δ 1.3 ppm more than 161.92 mM. Histopathology as gold standard. Statistical Tests Logistic regression and receiver operator characteristic (ROC) curves analysis. Results For both the training and validation datasets, the MDS score achieved an accuracy of 93.0% and 84.1%, significantly higher than that of morphology (88.4% and 79.5%), ADC value (74.4% and 68.2%), and spectroscopy (81.4% and 68.2%; P

Endometrial cancer (EC) is one of the most common gynecologic neoplasms in developed countries but lacks screening biomarkers. We aim to identify and validate metabolomic biomarkers in cervicovaginal fluid (CVF) for detecting EC through nuclear magnetic resonance (NMR) spectroscopy. We screened 100 women with suspicion of EC and benign gynecological conditions, and randomized them into the training and independent testing datasets using a 5:1 study design. CVF samples were analyzed using a 600-MHz NMR spectrometer equipped with a cryoprobe. Four machine learning algorithms—support vector machine (SVM), partial least squares discriminant analysis (PLS-DA), random forest (RF), and logistic regression (LR), were applied to develop the model for identifying metabolomic biomarkers in cervicovaginal fluid for EC detection. A total of 54 women were eligible for the final analysis, with 21 EC and 33 non-EC. From 29 identified metabolites in cervicovaginal fluid samples, the top-ranking metabolites chosen through SVM, RF and PLS-DA which existed in independent metabolic pathways, i.e. phosphocholine, malate, and asparagine, were selected to build the prediction model. The SVM, PLS-DA, RF, and LR methods all yielded area under the curve values between 0.88 and 0.92 in the training dataset. In the testing dataset, the SVM and RF methods yielded the highest accuracy of 0.78 and the specificity of 0.75 and 0.80, respectively. Phosphocholine, asparagine, and malate from cervicovaginal fluid, which were identified and independently validated through models built using machine learning algorithms, are promising metabolomic biomarkers for the detection of EC using NMR spectroscopy.

To develop and evaluate the performance of U-Net for fully automated localization and segmentation of cervical tumors in magnetic resonance (MR) images and the robustness of extracting apparent diffusion coefficient (ADC) radiomics features. This retrospective study involved analysis of MR images from 169 patients with cervical cancer stage IB–IVA captured; among them, diffusion-weighted (DW) images from 144 patients were used for training, and another 25 patients were recruited for testing. A U-Net convolutional network was developed to perform automated tumor segmentation. The manually delineated tumor region was used as the ground truth for comparison. Segmentation performance was assessed for various combinations of input sources for training. ADC radiomics were extracted and assessed using Pearson correlation. The reproducibility of the training was also assessed. Combining b0, b1000, and ADC images as a triple-channel input exhibited the highest learning efficacy in the training phase and had the highest accuracy in the testing dataset, with a dice coefficient of 0.82, sensitivity 0.89, and a positive predicted value 0.92. The first-order ADC radiomics parameters were significantly correlated between the manually contoured and fully automated segmentation methods (p

BackgroundComputed tomography (CT) has served as the first-line imaging modality but its role for detecting recurrent ovarian cancer should be revisited in the era of whole-body CT.PurposeTo study ...

Table S1. List of MR imaging features analyzed in the present study. (DOCX 18 kb)

BackgroundMost manufacturer manuals do not verify the use of dual energy X-ray absorptiometry for body composition analysis in subjects with a metal implant. This study aimed to quantify the effects of a spinal implant on body composition, and to determine whether unadjusted lean mass estimates are valid for patients with a spinal implant.MethodsA total of 30 healthy subjects were recruited. Three consecutive scans were performed for each participant, one with and two without extraneous spinal implant, without repositioning between scans. Lean, fat and bone estimates in the total body, trunk and limb were measured.ResultsPrecision errors for all total and regional body compositions were within the recommended ranges. Bone masses in the trunk and total body were significantly increased with spinal implant, and the increases exceeded the least significant change. For total and regional lean and fat estimates, the measurements between subjects with and without metal implants were in substantial to almost perfect agreement and the differences were not significant and did not exceed the least significant change.ConclusionsSpinal metal artifacts significantly increased the total body and trunk bone mass but the differences in lean- and fat-related estimates at total and regional body levels and all estimates in the extremity remained within the clinical acceptable range. Thus, a spinal implant may not compromise screening of patients for fat and lean masses using dual energy X-ray absorptiometry. Application of image reconstruction or a filtering algorithm may help reduce the effect of metallic artifacts and further study is needed.

To compare the diagnostic accuracy of diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for detecting cervical stromal invasion in endometrial cancer. Eighty-three consecutive women with endometrial cancer underwent preoperative evaluation in a 3-T unit, including T2-weighted, DW (b = 0 and 1000 s/mm2), and DCE MR imaging. Two radiologists independently assessed presence of cervical stromal invasion, with histopathological reference as gold standard. For assessing cervical stromal invasion, the diagnostic accuracy, sensitivity, and specificity, respectively for Reader 1/Reader 2, were as follows: DW MR imaging— 95.2 %/91.6 %, 91.7 %/100 %, and 95.8 %/90.1 %; DCE MR imaging— 91.6 %/88 %, 58.3 %/50 %, and 97.2 %/94.4 %. The diagnostic performance of DW MR imaging (Reader 1: areas under the receiver operating characteristic curve (AUC) = 0.98; Reader 2: AUC = 0.97) was significantly higher than that of DCE MR imaging (p = 0.009 for Reader 2) or T2-weighted MR imaging (Reader 1: p = 0.006; Reader 2: p = 0.013). Patients with cervical stromal invasion showed a significantly greater canal width (p

Purpose To assess the clinical value of proton (1H) MR spectroscopy in cervical carcinomas, in the prediction of poor prognostic human papillomavirus (HPV) genotypes as well as persistent disease following concurrent chemoradiotherapy (CCRT). Materials and Methods 1H MR spectroscopy using external phase array coil was performed in 52 consecutive cervical cancer patients at 3 Tesla (T). Poor prognostic HPV genotypes (alpha-7 species or absence of HPV infection) and persistent cervical carcinoma after CCRT were recorded. Statistical significance was calculated with the Mann-Whitney two-sided nonparametric test and areas under the receiver operating characteristics curve (AUC) analysis. Results A 4.3-fold (P = 0.032) increased level of methyl resonance at 0.9 ppm was found in the poor prognostic HPV genotypes, mainly attributed to the presence of HPV18, with a sensitivity of 75%, a specificity of 81%, and an AUC of 0.76. Poor prognostic HPV genotypes were more frequently observed in patients with adeno-/adenosquamous carcinoma (Chi-square, P

To develop and validate a prognostic model of integrating whole-tumour apparent diffusion coefficient (ADC) from pretreatment diffusion-weighted (DW) magnetic resonance (MR) imaging with human papillomavirus (HPV) genotyping in predicting the overall survival (OS) and disease-free survival (DFS) for women with stage IB–IV cervical cancer following concurrent chemoradiotherapy (CCRT). We retrospectively analysed three prospectively collected cohorts comprising 300 patients with stage IB–IV cervical cancer treated with CCRT in 2007–2014 and filtered 134 female patients who underwent MR imaging at 3.0 T for final analysis (age, 24–92 years; median, 54 years). Univariate and multivariate Cox regression analyses were used to evaluate the whole-tumour ADC histogram parameters, HPV genotyping and relevant clinical variables in predicting OS and DFS. The dataset was randomly split into training (n = 88) and testing (n = 46) datasets for construction and independent bootstrap validation of the models. The median follow-up time for surviving patients was 69 months (range, 9–126 months). Non-squamous cell type, ADC10

Abdominal aortic aneurysms (AAAs) are characterized by the destruction of elastin and collagen in the media and adventitia. Dipeptidyl peptidase-4 (DPP-4, an adipokine known as CD26) influences cell signaling, cell-matrix interactions, and the regulation of the functional activity of incretins in metabolic and inflammatory disorders. Although the role of DPP-4 in AAA evolution has been demonstrated, the underlying mechanisms of DPP-4-regulated AAA development remains unknown.Patients with AAA (n = 93) and healthy controls (CTL, n = 20) were recruited. Based on computed tomography image analyses, 93 patients were divided into two groups: those with a small AAA (SAA, aortic diameter 5 cm, n = 16) and those with a large AAA (LAA, aortic diameter ≥5 cm, n = 77). Plasma DPP-4, glucagon-like peptide-1 levels, and expression of CD26 on mononuclear cells were analyzed. In addition, phorbol 12-myristate 13-acetate (PMA)-induced THP-1 cells and angiotensin II-infused apolipoprotein EThe levels of DPP-4 (μU/μg) increased while active glucagon-like peptide-1 (pM) decreased in patients with AAA in a diameter-dependent manner [CTL: 2.3 ± 1.5 and 3.7 ± 2.4, respectively; SAA: 10.0 ± 10.9 and 2.1 ± 0.9, respectively; LAA: 32.2 ± 15.0 and 1.8 ± 1.1, respectively]. A significant decline in monocyte CD26 expression in patients with AAAs was observed relative to the CTL group. In vitro studies demonstrated that the inhibition of DPP-4 promoted PMA-induced monocytic cells differentiation, with increased CD68 and p21 expression, regulated by extracellular signal-regulated protein kinase 1/2 activation. Furthermore, inhibition of DPP-4 significantly increased the phosphorylation of PYK2 and paxillin in PMA-induced THP-1 cell differentiation. Finally, the animal study was used to confirm the in vitro results that LAA mice showed marked macrophage infiltration in the adventitia with a decreased expression of DPP-4 as compared with SAA mice.Increased plasma DPP-4 activity may correlate with aneurysmal development. CD26 on monocytes plays a critical role in cell differentiation, possibly mediated by extracellular signal-regulated protein kinase 1/2-p21 axis signaling pathways and cytoskeletal proteins reassembly. Exploring the role of DPP-4 further may yield potential therapeutic insights.

High molecular weight poly(butylene succinate) (PBSu), poly(propylene succinate), and PBSu-rich copolyesters were synthesized using an effective catalyst, titanium tetraisopropoxide. The compositions of the copolyesters were determined in three ways from 1H and 13C NMR spectra, and good agreement between the results was obtained. The analysis of the carbonyl carbon spectra indicates a random distribution of the comonomers. Thermal properties were studied using a differential scanning calorimeter and a thermogravimetric analyzer. No significant difference exists among the thermal stabilities of these polyesters. However, the window between the glass transition and the melting temperatures becomes narrower with the increase in the concentration of propylene succinate in the copolymers. Additionally, the cold crystallization ability reduces considerably. Wide-angle X-ray diffractograms of isothermally crystallized copolyesters also follow the same trend.

The copolyester was synthesized and characterized as having 92.7 mol % ethylene succinate units and 7.3 mol % butylene succinate (BS) units in a random sequence, as determined by the use of nuclear magnetic resonance. Isothermal crystallization kinetics of this copolyester was examined in the temperature range (Tc) from 30 to 80°C with the use of differential scanning calorimetry (DSC). The melting behavior after isothermal crystallization was studied with DSC by varying the Tc, the heating rate, and the crystallization time. The complex melting behavior involves both mechanisms of various lamellar crystals and melting–recrystallization–remelting. As the Tc increases, the contribution of recrystallization gradually decreases and finally disappears. The Hoffman–Weeks linear plot yielded an equilibrium melting temperature of 111.1°C, which is 1.6°C less than that of poly(ethylene succinate) (PES). The kinetic analysis of the spherulitic growth rates (G) indicated that a regime IIIII transition occurred at ∼59°C (TIIIII), which is ∼ 11°C less than that of PES. The overall crystallization rate, TIIIII and G indicate that the random incorporation of only 7.3 mol % BS units into PES significantly inhibits the crystallization rate of PES. Finally, the morphology of melt-crystallized samples was examined using polarized light microscopy and scanning electron microscopy. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

The copolyester was characterized as having 71 mol % trimethylene terephthalate units and 29 mol % ethylene terephthalate units in a random sequence according to the NMR spectra. Differential scanning calorimeter (DSC) was used to investigate the isothermal crystallization kinetics in the temperature range (Tc) from 130 to 170°C. The melting behavior after isothermal crystallization was studied using DSC and temperature-modulated DSC by varying the Tc, the crystallization time, and the heating rate. The DSC thermograms and wide-angle X-ray diffraction patterns reveal that the complex melting behavior involves melting-recrystallization-remelting and different lamellar crystals. As the Tc increases, the contribution of recrystallization gradually falls and finally disappears. A Hoffman-Weeks linear plot yields an equilibrium melting temperature of 198.7°C. The kinetic analysis of the growth rates of spherulites and the change in the morphology from regular to banded spherulites indicate that a regime II→III transition occurs at 148°C. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Poly(ethylene succinate) (PES) and its copolyesters that contain 7, 10, or 48 mol % butylene succinate (BS) were synthesized through a direct polycondensation reaction with titanium tetraisopropoxide as the catalyst. Measurements of intrinsic viscosity (1.08–1.27 dL/g) proved the success of the preparation of polyesters with high molecular weights. The compositions and the sequence distributions of the copolyesters were determined from 1H and 13C NMR spectra. The distributions of ethylene succinate and BS units were found to be random. Their thermal properties were elucidated using a differential scanning calorimeter (DSC) and a thermogravimetric analyzer. No significant difference exists among the thermal stabilities of these polyesters. All of the copolymers exhibit a single glass transition temperature. Wide-angle X-ray diffractograms (WAXD) were obtained from polyesters that were crystallized isothermally. The DSC thermograms and WAXD patterns indicate that the incorporation of BS units into PES significantly inhibits the crystallization behavior of PES. The heat of fusion of ideal PES crystals is 163 J/g, as determined by the depression of the melting point of PES crystals in acetophenone. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Copolyester was synthesized and characterized as having 89.9 mol % ethylene succinate units and 10.1 mol % butylene succinate units in a random sequence, as revealed by NMR. Isothermal crystallization kinetics was studied in the temperature range (Tc) from 30 to 73 °C using differential scanning calorimetry (DSC). The melting behavior after isothermal crystallization was investigated using DSC by varying the Tc, the heating rate and the crystallization time. DSC curves showed triple melting peaks. The melting behavior indicates that the upper melting peaks are associated primarily with the melting of lamellar crystals with various stabilities. As the Tc increases, the contribution of recrystallization slowly decreases and finally disappears. A Hoffman-Weeks linear plot gives an equilibrium melting temperature of 107.0 °C. The spherulite growth of this copolyester from 80 to 20 °C at a cooling rate of 2 or 4 °C/min was monitored and recorded using an optical microscope equipped with a CCD camera. Continuous growth rates between melting and glass transition temperatures can be obtained after curve-fitting procedures. These data fit well with those data points measured in the isothermal experiments. These data were analyzed with the Hoffman and Lauritzen theory. A regime II → III transition was detected at around 52 °C. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2431–2442, 2008

Poly(ethylene succinate) (PES), poly(trimethylene succinate) (PTS) and their copolyesters with various compositions were synthesized through a direct polycondensation reaction with titanium tetraisopropoxide as the catalyst. The results of intrinsic viscosity and GPC have proven successful in preparing high molecular weight polyesters. The compositions and the sequence distributions of the copolyesters were determined by analyses of 1H NMR and 13C NMR spectra. The sequence distributions of ethylene succinate units and trimethylene succinate (TS) units were found to be random. Their thermal properties were characterized using differential scanning calorimeter and thermal gravimetric analyzer. All of the copolymers exhibit a single glass transition temperature (Tg). There is no significant difference in the thermal stability among these polyesters. Wide angle X-ray diffractograms (WAXD) were obtained for polyesters which can be crystallized isothermally. The results of thermal analysis and the WAXD patterns indicate that the incorporation of TS units into PES significantly inhibits the crystallization behavior of PES. Additionally, the crystal pattern of PTS is quite different from that of PES. Dynamic mechanical properties of moldable polyesters were investigated using a Rheometer operated at 1 Hz. Below Tg, the incorporation of TS units into PES results in the decline of storage modulus. Above Tg, the effect of crystallinity on the storage modulus can be found.

Copolyester was synthesized and characterized as having 94.4 mol% ethylene succinate units and 5.6 mol% trimethylene succinate units in a random sequence as revealed by NMR. Differential scanning calorimeter (DSC) was used to investigate the isothermal crystallization kinetics of this copolyester in the temperature range ( T c ) from 30 to 80 °C. The melting behavior after isothermal crystallization was studied by using DSC and temperature modulated DSC (TMDSC) by varying the T c , the heating rate and the crystallization time. DSC and TMDSC curves showed triple melting peaks. The melting behavior indicates that the upper melting peaks are primarily due to the melting of lamellar crystals with different stabilities. A small exothermic curve between the main melting peaks gives a direct evidence of recrystallization. As the T c increases, the contribution of recrystallization gradually decreases and finally disappears. The Hoffman–Weeks linear plot gave an equilibrium melting temperature of 108.3 °C. The kinetic analysis of the spherulitic growth rates indicated that a regime II → III transition occurred at ∼65 °C.

A copolyester was synthesized and characterized to have 78.6 mol% ethylene succinate unit and 21.4 mol% trimethylene succinate unit by using NMR. The value of the random parameter is 0.97 that can be considered to be a random copolymer. The melting behavior after isothermal crystallization was studied using differential scanning calorimeter by varying the crystallization temperature, the heating rate and the crystallization time. Triple melting peaks were observed. The melting behavior indicates that the upper melting peaks are primarily due to the melting of lamellar crystals with different stability. The Hoffman–Weeks linear plot gives an equilibrium melting temperature of 94.0 °C. The spherulite growth of this copolyester from 72 °C to 30 or 15 °C at a cooling rate of 1 or 2 °C/min was monitored and recorded using an optical microscope equipped with a CCD camera and a DVD recorder. These experiments including the self-nucleation pretreatment took 72 min and 60 min, respectively. Continuous growth rates between melting and glass transition temperatures can be obtained after curve-fitting procedures. These data fit well with those data points measured in the isothermal experiments, which is time consuming. These isothermal and continuous data were separately analyzed with the Hoffman and Lauritzen theory. A regime II–III transition was detected at about 51.5 ± 0.1 °C.

Abdominal aortic aneurysm (AAA) is a life-threatening situation affecting almost 10% of elders. There has been no effective medication for AAA other than surgical intervention. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to have a protective effect on cardiovascular disease. Whether DPP-4 inhibitors may be beneficial in the treatment of AAA is unclear. We investigated the effects of DPP-4 inhibitor sitagliptin on the angiotensin II (Ang II)-infused AAA formation in apoE-deficient (apoE-/-) mice. Mice with induced AAA were treated with placebo or 2.5, 5 or 10 mg/kg/day sitagliptin. Ang II-infused apoE-/- mice exhibited a 55.6% incidence of AAA formation, but treatment with sitagliptin decreased AAA formation. Specifically, administered sitagliptin in Ang II-infused mice exhibited decreased expansion of the suprarenal aorta, reduced elastin lamina degradation of the aorta, and diminished vascular inflammation by macrophage infiltration. Treatment with sitagliptin decreased gelatinolytic activity and apoptotic cells in aorta tissues. Sitaglipitn, additionally, was associated with increased levels of plasma active glucagon-like peptide-1 (GLP-1). In vitro studies, GLP-1 decreased reactive oxygen species (ROS) production, cell migration, and MMP-2 as well as MMP-9 activity in Ang II-stimulated monocytic cells. The results conclude that oral administration of sitagliptin can prevent abdominal aortic aneurysm formation in Ang II-infused apoE-/-mice, at least in part, by increasing of GLP-1 activity, decreasing MMP-2 and MMP-9 production from macrophage infiltration. The results indicate that sitagliptin may have therapeutic potential in preventing the development of AAA.

Poly(ethylene succinate) (PES), poly(butylene succinate) (PBS), and PES-rich copolyesters were synthesized using an effective catalyst, titanium tetraisopropoxide. PES was blended with minor amounts of PBS for the comparison. The compositions of the copolyesters and the blends were determined from NMR spectra. Their thermal properties were studied using a differential scanning calorimeter (DSC), a temperature modulated DSC (TMDSC), and a thermogravimetric analyzer. No significant difference exists among the thermal stabilities of these polyesters and blends. For the blends, the reversible curves of TMDSC showed a distinct glass-rubber transition temperature (Tg), however, the variation of the Tg values with the blend compositions was small. Isothermal crystallization kinetics and the melting behavior after crystallization were examined using DSC. Wide-angle X-ray diffractograms (WAXD) were obtained for the isothermally crystallized specimens. The results of DSC and WAXD indicate that the blends have a higher degree of crystallinity and a higher melting temperature than those of the corresponding copolymers. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

The aim of this study was to find the time window for monitoring early radiation-induced liver injury (RILI) of rats using ferucarbotran-enhanced magnetic resonance imaging (MRI) at 3 T. Six rats were irradiated with 20 Gy 6 MV X-ray on right side liver and the other six non-irradiated rats were used as the control. Three or four days after irradiation, the rats were examined using MRI. The conventional spin echo (CSE) pulse sequence with various scanning parameters (CSE1: TR/TE = 200/8 ms, CSE2: TR/TE = 1000/8 ms and CSE3: TR/TE = 1000/22 ms) was performed before, 20 min, 1 h, 7 days, 14 days and 21 days after injecting 80 μmol/kg ferucarbotran, a kind of commercialized superparamagnetic iron oxide (SPIO). The ferucarbotran particles were macrophaged by Kupffer cells and this caused decreased signal intensity on MR images because of the T2and susceptibility effect. The irradiated liver had less reduction of MR signal intensity than the non-irradiated liver because radiation impaired the function of Kupffer cells. All CSE images of the irradiated group showed higher right-to-left ratio of the MR signal intensity in the liver than the control group after ferucarbotran injection. Furthermore, CSE2 demonstrated higher efficacy than CSE1 and CSE3. The optimal time window to observe an obvious contrast between the right side and left side liver in the irradiated group was from 20 min to 7 days after a single bolus injection of ferucarbotran. This protocol may be helpful to investigate the effects of radioprotectors and radiosensitizers on the reticuloendothelial system.