Background
Due to their location and growth patterns, retroperitoneal tumors often involve the surrounding blood vessels. Clinical decisions on a proper treatment depend on the information on this ...condition. Evaluation of blood vessels using non‐contrast‐enhanced vessel wall MRI may provide noninvasive assessment of the extent of tumor invasion to assist clinical decision‐making.
Purpose
To investigate the performance and potential of non‐contrast‐enhanced vessel wall MRI in evaluating the degree of vessel wall invasion of retroperitoneal tumors.
Study Type
Prospective.
Population
Thirty‐seven participants (mean age: 60.59 ± 11.77 years, 59% male) with retroperitoneal tumors close to vessels based on their diagnostic computer tomography.
Field Strength/Sequences
3 T; vessel wall MRI sequences: two‐dimensional T2‐weighted MultiVane XD turbo spin‐echo (2D‐T2‐MVXD‐TSE) and three‐dimensional T1‐weighted motion sensitized driven equilibrium fat suppression turbo spin‐echo (3D‐T1‐MSDE‐TSE) sequences; conventional MRI sequences: T2‐weighted fat suppression turbo spin‐echo (T2‐FS‐TSE), T2‐weighted turbo spin‐echo (T2‐TSE), modified Dixon T1‐weighted fast field echo (T1‐mDixon‐FFE), and diffusion‐weighted echo planar imaging (DWI‐EPI) sequences.
Assessment
All patients underwent preoperative imaging using both non‐contrast conventional and vessel wall MRI sequences. Images obtained from conventional and vessel wall MRI sequences were evaluated independently by three junior radiologists (3 and 2 years of experience in reading MRI) and reviewed by one senior radiologist (25 years of experience in reading MRI) to assess the degree of vessel wall invasion. MRI were validated results from the clinical standard diagnosis based on surgical confirmation or histopathological reports. Interobserver agreement was determined based on the reports from three readers with similar years of experiences. Intraobserver variability was assessed based on categorizing and recategorizing the vessels of 37 patients 1 month apart.
Statistical Tests
Intra‐class correlation efficient (ICC), Chi‐square test, McNemar test, area under the receiver‐operating characteristic curve (AUC), Delong test, P < 0.05 was considered significant.
Results
The accuracy of vessel wall MRI (91.96%, 95% CI: 85.43–95.71; 103 of 112) in detecting the degree of vessel wall invasion was significantly higher than that of conventional MRI (75%, 95% CI: 66.24–82.10; 84 of 112). The interobserver variability or reproducibility in categorization of the degree of vascular wall invasion was good in evaluating images from conventional and vessel wall MRI sequences (ICC = 0.821, 95% CI: 0.765–0.867 and ICC = 0.881, 95% CI: 0.842–0.913, respectively).
Data Conclusion
Diagnosis of vessel wall invasion of retroperitoneal tumors and assessment of its severity can be improved by using non‐contrast‐enhanced vessel wall MRI.
Evidence Level
1
Technical Efficacy
Stage 3
Azole compounds are an important class of nitrogen heterocycles with electron-rich property. This special structure endows azole-based derivatives easily bind with the enzymes and receptors in ...organisms through noncovalent interactions such as hydrogen bonds, coordination bonds, ion-dipole, cation-π,π-π stacking and hydrophobic effect as well as van der Waals force etc., thereby possessing various applications in medicinal chemistry, especially their protrudent effects such as imidazoles and triazoles against fungal strains. The design, synthesis and antimicrobial activity of azole derivatives have been extensively investigated and have become one of the highly active highlights in recent years, and the progress is quite rapid. In particular, a large number of azole-based antibacterial and antifungal agents have been penetratingly studied as candidates and even some of them have been used in clinic, which have shown the great potential and development value of azole compounds. Based on our researches on azole compounds and referring to other literature, this work scientifically reviewed the researches and developments of azole-based compounds as antibacterial and antifungal agents, including oxazole, imidazole, benzimidazole, triazole, benzotriazole, pyrazole, thiazole, carbazole as well as tetrazole in recent three years. It is hopeful that azole compounds may continue to serve as an important direction for the exploitation of azole-based antibacterial and antifungal drugs with better curative effect, lower toxicity, less side effects, especially fewer resistances and so on.
Among all dielectrics, antiferroelectric (AFE) materials have attracted wide attention due to the excellent energy-storage performance. In this paper, PbHfO3 (PHO) AFE films were prepared for the ...first time and the microstructure, AFE property and energy-storage performance were studied. X-ray diffraction analysis indicated that annealing temperature played a key role in the crystallinity and phase composition. Due to the coexistent of fine grains and amorphous phase, PHO AFE films annealed at 650 °C displayed not only optimal energy-storage density and energy efficiency, but also excellent thermal stability and fatigue endurance. Compared with films annealed at 750 °C, the recoverable energy-storage density and energy efficiency in 650 °C annealing samples increased by 50% and 100%, respectively. These results demonstrate that PHO film is a promising candidate for applications in power electronics systems.
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•Novel PbHfO3 antiferroelectric films were prepared for the first time.•The 650 °C annealed film has high recoverable energy storage density and energy efficiency.•The energy storage performance can be improved effectively by cutting components through proper annealing process.
Fine microparticles of poly(p‐phenylenediamine) (PpPD) and poly(m‐phenylenediamine) (PmPD) were directly synthesized by a facile oxidative precipitation polymerization and their strong ability to ...adsorb lead ions from aqueous solution was examined. It was found that the degree of adsorption of the lead ions depends on the pH, concentration, and temperature of the lead ion solution, as well as the contact time and microparticle dose. The adsorption data fit the Langmuir isotherm and the process obeyed pseudo‐second‐order kinetics. According to the Langmuir equation, the maximum adsorption capacities of lead ions onto PpPD and PmPD microparticles at 30 °C are 253.2 and 242.7 mg g−1, respectively. The highest adsorptivity of lead ions is up to 99.8 %. The adsorption is very rapid with a loading half‐time of only 2 min as well as initial adsorption rates of 95.24 and 83.06 mg g−1 min−1 on PpPD and PmPD particles, respectively. A series of batch experiment results showed that the PpPD microparticles possess an even stronger capability to adsorb lead ions than the PmPD microparticles, but the PmPD microparticles, with a more‐quinoid‐like structure, show a stronger dependence of lead‐ion adsorption on the pH and temperature of the lead‐ion solution. A possible adsorption mechanism through complexation between Pb2+ ions and N groups on the macromolecular chains has been proposed. The powerful lead‐ion adsorption on the microparticles makes them promising adsorbents for wastewater cleanup.
Taking the lead: The adsorption data of Pb2+ ions onto poly(phenylenediamine) microparticles fit the Langmuir isotherm and follow pseudo‐second‐order kinetics. The maximum Pb2+ ion adsorbance and adsorptivity are 253 mg g−1 and 99.8 %, respectively (see picture). The adsorption is very rapid with a loading half‐time of 2 min and an adsorption rate of 95 mg g−1 min−1. A complexation mechanism between Pb2+ ions and N groups has been proposed.
Available therapeutic strategies are urgently needed to conquer multidrug resistance of MRSA. A visible effort was guided towards the advancement of novel antibacterial framework of naphthalimide ...corbelled aminothiazoximes, and desired to assert some insight on the conjunction of individual pharmacophore with distinct biological activities and unique action mechanism. Preliminary assessment displayed that dimethylenediamine derivative 13d presented a wonderful inhibition on MRSA (MIC = 0.5 μg/mL), and showed excellent membrane selectivity (HC50 > 200 μg/mL) from an electrostatic distinction of the electronegative bacterial membranes and the electroneutral mammalian membranes. Moreover, 13d could effectually relieve the development of MRSA resistance. Investigations into explaining the mechanism of anti-MRSA disclosed that 13d displayed strong lipase affinity, which facilitated its permeation into cell membrane, causing membrane depolarization, leakage of cytoplasmic contents and lactate dehydrogenase (LDH) inhibition. Meanwhile, 13d could exert interaction with DNA to hinder biological function of DNA, and disrupt the antioxidant defense system of MRSA through up-regulation of ROS subjected the strain to oxidative stress. In particular, the unanticipated mechanism for naphthalimide corbelled aminothiazoximes that 13d could suppress the expression of PBP2a by inducing allosteric modulation of PBP2a and triggering the open of the active site, was discovered for the first time. These findings of naphthalimide corbelled aminothiazoximes as a small-molecule class of anti-MRSA agents held promise in strategies for treatment of MRSA infections.
A desirable family of unique naphthalimide corbelled aminothiazoximes as novel antibacterials were exploited. Experimental investigation with membrane destruction, inhibition of LDH, protein leakage, oxidative damage, DNA interaction and allosteric modulation of PBP2a suggested possible antibacterial mechanism. Display omitted
•Novel naphthalimide corbelled aminothiazoximes as antibacterials were exploited.•Compound 13d possessed low toxicity, safe hemolysis level and no resistance.•Compound 13d presented lipase affinity and caused membrane disruption.•Compound 13d could destroy antioxidant defense system and lead to oxidative damage.•Compound 13d could bind to the allosteric site of PBP2a to resurrect older drugs.
This study aimed to track and evaluate the effect of low-dose irisin on the browning of white adipose tissue (WAT) in mice using magnetic resonance imaging (MRI) noninvasively in vivo. Mature white ...adipocytes extracted from mice were cultured, induced and characterized before being treated by irisin. The volume and fat fraction of WAT were quantified using MRI in normal chow diet and high fat mice after injection of irisin. The browning of cultured white adipocytes and WAT in mice were validated by immunohistochemistry and western blotting for uncoupling protein 1 (UCP1) and deiodinase type II (DIO2). The serum indexes were examined with high fat diet after irisin intervention. UCP1 and DIO2 in adipocytes showed increases responding to the irisin treatment. The size of white adipocytes in mice receiving irisin intervention was reduced. MRI measured volumes and fat fraction of WAT were significantly lower after Irisin treatment. Blood glucose and cholesterol levels were reduced in high fat diet mice after irisin treatment. Irisin intervention exerted browning of WAT, resulting reduction of volume and fat fraction of WAT as measured by MRI. Furthermore, it improved the condition of mice with diet-induced obesity and related metabolic disorders.
In the case of dielectric energy storage devices, excessive pursuit of giant electric fields means greater exposure to high temperatures and insulation damage risk. Ferroelectric thin film devices ...offer opportunities for energy storage needs under finite electric fields due to their intrinsically large polarization and the advantage of small size. Herein, we designed the capacitor's dielectric layer by doping barium titanate Ba (1-x) Ce x TiO 3 (BCTO). The addition of highly charged ions Ce 3+ induce cell shrinkage thus further optimizing the ferroelectric polarization. Accordingly, the capacitor with Au/BCTO/Au structure integrated directly on silicon substrate showed excellent energy storage performance ( W rec ≈ 92.6 J/cm 3 and η ≈ 86.5%) under only 1961 kV/cm. In addition, we significantly increased the electrical breakdown strength from 1726 kV/cm to 3426 kV/cm by adjusting the Ba 0.95 Ce 0.05 TiO 3 film thickness, thus achieving ultra-high energy storage density (107.9 J/cm 3 ). The results expand the application prospects of silicon-based ferroelectric capacitors for energy storage at low electric field strength.
Background: Up to 80% of pancreatic cancer patients suffer from cachexia. White adipose tissue (WAT) browning caused by the tumorigenicity and progression aggravates the cancer-associated cachexia ...(CAC). Cancer-initiated changes in the protein-38 mitogen-activated protein kinases (p38 MAPK) pathway are likely involved in the development of CAC. Methods: p38 MAPK inhibitors, VCP979 or SB203580, were used in the in vitro and in vivo models of pancreatic cancer cachexia. Expression of uncoupling protein 1 (UCP1) in the p38 MARK pathway and the properties and level of white adipocytes were analyzed and correlated to browning, followed by immunohistochemistry and Western blotting validations. Changes in the volume and fat fraction of WAT in animals were monitored by magnetic resonance imaging (MRI). Results: The size of white adipocytes was increased after being treated with the p38 MAPK inhibitors, along with increase in the MRI-measured volume and fat fraction of WAT. Comparing two p38 MAPK inhibitors, the p38α subunit-specific inhibitor VCP979 had a better therapeutic effect than SB203580, which targets both p38α and β subunits. Conclusions: Blockade of p38 MAPK reduced the WAT browning that contributes to CAC. Thus, p38 MARK inhibitors can potentially be used as a therapy for treating CAC. Non-invasive MRI can also be applied to assess the progression and treatment responses of CAC.
Mitochondrial RNA metabolism is suggested to occur in identified compartmentalized foci, i.e. mitochondrial RNA granules (MRGs). Mitochondrial aminoacyl-tRNA synthetases (mito aaRSs) catalyze tRNA ...charging and are key components in mitochondrial gene expression. Mutations of mito aaRSs are associated with various human disorders. However, the suborganelle distribution, interaction network and regulatory mechanism of mito aaRSs remain largely unknown. Here, we found that all mito aaRSs partly colocalize with MRG, and this colocalization is likely facilitated by tRNA-binding capacity. A fraction of human mitochondrial AlaRS (hmtAlaRS) and hmtSerRS formed a direct complex via interaction between catalytic domains in vivo. Aminoacylation activities of both hmtAlaRS and hmtSerRS were fine-tuned upon complex formation in vitro. We further established a full spectrum of interaction networks via immunoprecipitation and mass spectrometry for all mito aaRSs and discovered interactions between hmtSerRS and hmtAsnRS, between hmtSerRS and hmtTyrRS and between hmtThrRS and hmtArgRS. The activity of hmtTyrRS was also influenced by the presence of hmtSerRS. Notably, hmtSerRS utilized the same catalytic domain in mediating several interactions. Altogether, our results systematically analyzed the suborganelle localization and interaction network of mito aaRSs and discovered several mito aaRS-containing complexes, deepening our understanding of the functional and regulatory mechanisms of mito aaRSs.
This work did a new exploration towards aminothiazolquinolone oximes as potentially multi-targeting antimicrobial agents. A class of novel hybrids of quinolone, aminothiazole, piperazine and oxime ...fragments were designed for the first time, conveniently synthesized as well as characterized by 1H NMR, 13C NMR and HRMS spectra. Biological activity showed that some of the synthesized compounds exhibited good antimicrobial activities in comparison with the reference drugs. Especially, O-methyl oxime derivative 10b displayed excellent inhibitory efficacy against MRSA and S. aureus 25923 with MIC values of 0.009 and 0.017 mM, respectively. Further studies indicated that the highly active compound 10b showed low toxicity toward BEAS-2B and A549 cell lines and no obvious propensity to trigger the development of bacterial resistance. Quantum chemical studies have also been conducted and rationally explained the structural features essential for activity. The preliminarily mechanism exploration revealed that compound 10b could not only exert efficient membrane permeability by interfering with the integrity of cells, bind with topoisomerase IV–DNA complex through hydrogen bonds and π-π stacking, but also form a steady biosupramolecular complex by intercalating into DNA to exert the efficient antibacterial activity. The supramolecular interaction between compound 10b and human serum albumin (HSA) was a static quenching, and the binding process was spontaneous, where hydrogen bonds and van der Waals force played vital roles in the supramolecular transportation of the active compound 10b by HSA.
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•Novel aminothiazolquinolone oxime derivatives as potentially multi-targeting antimicrobial agents were developed.•O-methyl oxime derivative 10b displayed excellent inhibitory efficacy against MRSA and S. aureus 25923 with MIC values of 0.009 and 0.017 mM, respectively.•Compound 10b showed broad antimicrobial spectrum, low toxicity and quite slow development of resistance.•Molecule 10b could bind with topoisomerase IV–DNA complex through hydrogen bonds and π-π stacking.•Compound 10b could intercalate DNA and bind to human serum albumin.