High-resolution Magnetic Resonance Research Articles

Genome Mining and Molecular Networking Guided Isolation of Antimycin Analogs with Antifeedant Activities from the Deep-Sea-Derived Streptomyces sp. NA13.

Polyphagous insects could affect agricultural production, which leads to serious economic losses. Due to the negative effects of synthesized insecticides, finding eco-friendly and new biopesticides is emergent. To develop natural origin insecticides, an integrative approach combining antifeedant activity screening, genome mining, and molecular networking has been applied to discover antifeedant secondary metabolites from Streptomyces sp. NA13, which leads to the isolation of a novel antimycin Q (1) and six known antimycin analogs (antimycins A1a, A2a, A3a, A4a, A7a, and N-formylantimycic acid methyl ester, 2-7). Their structures were identified by high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopic. The absolute configuration of 1 was elucidated by the comparison of coupling constant, electronic circular dichroism (ECD) analysis, and NMR calculations. 1-6 exhibited different levels of antifeedant activities against Helicoverpa armigera, especially 1-4. At the same time, the antifeedant activity of antimycin was reported firstly.

Determining the Predominant Conformations of Mortiamides A-D in Solution Using NMR Data and Molecular Modeling Tools.

Macrocyclic peptidomimetics have been seriously contributing to our arsenal of drugs to combat diseases. The search for nature's discoveries led us to mortiamides A-D (found in a novel fungus from Northern Canada), which is a family of cyclic peptides that clearly have demonstrated impressive pharmaceutical potential. This prompted us to learn more about their solution-state properties as these are central for binding to target molecules. Here, we secured and isolated mortiamide D, and then acquired high-resolution nuclear magnetic resonance (NMR) data to learn more about its structure and dynamics attributes. Sets of two-dimensional NMR experiments provided atomic-level (through-bond and through-space) data to confirm the primary structure, and NMR-driven molecular dynamics (MD) simulations suggested that more than one predominant three-dimensional (3D) structure exist in solution. Further steps of MD simulations are consistent with the finding that the backbones of mortiamides A-C also have at least two prominent macrocyclic shapes, but the side-chain structures and dynamics differed significantly. Knowledge of these solution properties can be exploited for drug design and discovery.

Location of the AICA influences the severity but not occurrence of ISSNHL: A reappraisal using high-resolution 3 T MRI

ObjectiveTo investigate the potential influence of anatomical variation in the anterior inferior cerebellar artery (AICA) on the occurrence and severity of idiopathic sudden sensorineural hearing loss (ISSNHL). MethodsNinety ISSNHL patients were enrolled. The anatomical location of the AICA was exhibited using high-resolution magnetic resonance imaging (MRI), and the various AICA types classified by previously reported Chavda and Gorrie methods were analyzed. The severity of hearing loss in the ipsilateral ear among different AICA types was compared. ResultsApproximately 85.6% of subjects had unilateral ISSNHL (uISSNHL), and the others had bilateral ISSNHL (bISSNHL). In the uISSNHL group, the ratios of different AICA types were similar between the ipsilateral and contralateral ears. The ratios of the different AICA types in the bISSNHL group were similar to those in the uISSNHL group. In the uISSNHL group, pure tone audiometry (PTA) thresholds at 2 kHz, 4 kHz and 8 kHz of patients with Chavda type II AICA were higher than those of patients with Chavda type I and type III, with a significant difference at 4 kHz between type I and type II. There was a tendency of the PTA threshold in patients with Chavda type II or Gorrie type C to gradually increase from low to high frequency zones. ConclusionWhen the AICA enters the IAC (Chavda type II) or crosses between the 7th and 8th cranial nerves (Gorrie type C), the severity and frequency of hearing impairment in ISSNHL but not the occurrence of ISSNHL will be affected.

Transcriptional level of inflammation markers associates with short-term brain structural changes in first-episode schizophrenia

BackgroundInflammation has been implicated in the pathology of schizophrenia and may cause neuronal cell death and dendrite loss. Neuroimaging studies have highlighted longitudinal brain structural changes in patients with schizophrenia, yet it is unclear whether this is related to inflammation. We aim to address this question, by relating brain structural changes with the transcriptional profile of inflammation markers in the early stage of schizophrenia.MethodsThirty-eight patients with first-episode schizophrenia and 51 healthy controls were included. High-resolution T1-weighted magnetic resonance imaging (MRI) and clinical assessments were performed at baseline and 2 ~ 6 months follow-up for all subjects. Changes in the brain structure were analyzed using surface-based morphological analysis and correlated with the expression of immune cells-related gene sets of interest reported by previous reviews. Transcriptional data were retrieved from the Allen Human Brain Atlas. Furthermore, we examined the brain structural changes and peripheral inflammation markers in association with behavioral symptoms and cognitive functioning in patients.ResultsPatients exhibited accelerated cortical thickness decrease in the left frontal cortices, less decrease or an increase in the superior parietal lobule and right lateral occipital lobe, and increased volume in the bilateral pallidum, compared with controls. Changes in cortical thickness correlated with the transcriptional level of monocyte across cortical regions in patients (r = 0.54, p < 0.01), but not in controls (r = − 0.05, p = 0.76). In addition, cortical thickness change in the left superior parietal lobule positively correlated with changes in digital span-backward test scores in patients.ConclusionsPatients with schizophrenia exhibit regional-specific cortical thickness changes in the prefrontal and parietooccipital cortices, which is related to their cognitive impairment. Inflammation may be an important factor contributing to cortical thinning in first-episode schizophrenia. Our findings suggest that the immunity-brain-behavior association may play a crucial role in the pathogenesis of schizophrenia.

Constituents of the fruits of Rubus chingii Hu and their neuroprotective effects on human neuroblastoma SH-SY5Y cells

Rubi fructus (Rubus chingii Hu) is a fruit of Rubus genus and is used in medicine and food applications. In this study, eight new phenylpropanoids (1–8) and seven known compounds (9–15) were isolated from the dried fruits of Rubus chingii Hu, and their structures were characterized through high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. Electronic circular dichroism (ECD) experiments were performed, and the results were compared with ECD spectra. Compound 3 was characterized through extensive single crystal X-ray diffraction. Evaluation of the neuroprotective pharmacological activities revealed that compounds 6, 7, 9, and 14 exerted protective effects against H2O2-induced neurotoxicity by reducing the reactive oxygen species levels at concentrations of 50 and 100 μM. Moreover, the three compounds 6, 9, and 14 significantly inhibited the expression of the Casp3 gene at a concentration of 50 μM. Compounds 7 and 9 effectively repressed the expression of the MYC gene. Compounds 6 and 9 obviously upregulated the ratio of Bcl2/Bax in SH-SY5Y cells and inhibited cell apoptosis. The study results can be used as a reference for the development of R. chingii products to realize their neuroprotective functions in the future.

Radiomics and artificial neural networks modelling for identification of high-risk carotid plaques.

In this study, we aimed to investigate the classification of symptomatic plaques by evaluating the models generated via two different approaches, a radiomics-based machine learning (ML) approach, and an end-to-end learning approach which utilized deep learning (DL) techniques with several representative model frameworks. We collected high-resolution magnetic resonance imaging (HRMRI) data from 104 patients with carotid artery stenosis, who were diagnosed with either symptomatic plaques (SPs) or asymptomatic plaques (ASPs), in two medical centers. 74 patients were diagnosed with SPs and 30 patients were ASPs. Sampling Perfection with Application-optimized Contrasts (SPACE) by using different flip angle Evolutions was used for MRI imaging. Repeated stratified five-fold cross-validation was used to evaluate the accuracy and receiver operating characteristic (ROC) of the trained classifier. The two proposed approaches were investigated to train the models separately. The difference in the model performance of the two proposed methods was quantitatively evaluated to find a better model to differentiate between SPs and ASPs. 3D-SE-Densenet-121 model showed the best performance among all prediction models (AUC, accuracy, precision, sensitivity, and F1-score of 0.9300, 0.9308, 0.9008, 0.8588, and 0.8614, respectively), which were 0.0689, 0.1119, 0.1043, 0.0805, and 0.1089 higher than the best radiomics-based ML model (MLP). Decision curve analysis showed that the 3D-SE-Densenet-121 model delivered more net benefit than the best radiomics-based ML model (MLP) with a wider threshold probability. The DL models were able to accurately differentiate between symptomatic and asymptomatic carotid plaques with limited data, which outperformed radiomics-based ML models in identifying symptomatic plaques.

High resolution solid-state NMR on the desktop

High-resolution low-field nuclear magnetic resonance (NMR) spectroscopy has found wide application for characterization of liquid compounds because of the low maintenance cost of modern permanent magnets. Solid-state NMR so far is limited to low-resolution measurements of static powders, because of the limited space available in this type of magnet. Magic-angle sample spinning and low-magnetic fields are an attractive combination to achieve high spectral resolution especially for paramagnetic solids. Here we show that magic angle spinning modules can be miniaturized using 3D printing techniques so that high-resolution solid-state NMR in permanent magnets becomes possible. The suggested conical rotor design was developed using finite element calculations and provides sample spinning frequencies higher than 20 kHz. The setup was tested on various diamagnetic and paramagnetic compounds including paramagnetic battery materials. The only comparable experiments in low-cost magnets known so far, had been done in the early times of magic angle spinning using electromagnets at much lower sample spinning frequency. Our results demonstrate that high-resolution low-field magic-angle-spinning NMR does not require expensive superconducting magnets and that high-resolution solid-state NMR spectra of paramagnetic compounds are feasible. Generally, this could introduce low-field solid-state NMR for abundant nuclei standard as a routine analytical tool.

A2OURSR: Adaptive adjustment based real MRI super-resolution via opinion-unaware measurements.

High-quality and high-resolution magnetic resonance (MR) images can provide more details for diagnosis and analyses. Recently, MR images guided neurosurgery has become an emerging technique in clinics. Unlike other medical imaging techniques, it is impossible to achieve both real-time imaging and high image quality in MR imaging. The real-time performance is closely related to the nuclear magnetic equipment itself as well as the collection strategy of the k space data. Optimizing the imaging time cost via the corresponding algorithm is harder than enhancing image quality. Further, in reconstructing low-resolution and noise-rich MR images, getting relatively high-definition and resolution MR images as references are difficult or impossible. In addition, the existing methods are restricted in learning the controllable functions under the supervision of known degradation types and levels. As a result, severely bad results are inevitable when the modeling assumptions are far apart from the actual situation. To address these problems, we propose a novel adaptive adjustment method based on real MR images via opinion-unaware measurements for real super-resolution (A2OURSR). It can estimate the degree of blur and noise from the test image itself using two scores. These two scores can be considered pseudo labels to train the adaptive adjustable degradation estimation module. Then, the outputs of the above model are used as the inputs of the conditional network to tweak the generated results. Thus, the results can be automatically adjusted via the whole dynamic model. Extensive experimental results show that the proposed A2OURSR is superior to state-of-the-art methods on benchmarks quantitatively and visually.

Synthesis of a new diarylhydrazone derivative and an evaluation of its in vitro biofilm inhibition and quorum sensing disruption along with a molecular docking study

Molecules that target quorum sensing and biofilm inhibition are useful antimicrobials. In this regard, a new diarylhydrazone was synthesized and characterized using infrared, high-resolution mass spectrometry and nuclear magnetic resonance experiments as N-[( E)-4-bromo-2,5-diheptyloxybenzylideneamino]-2,4-dinitroaniline (BHBANA). Minimal inhibitory concentrations (MICs) vary from 0.625 to 2.5 mg mL−1. This compound was screened in vitro for its inhibition of quorum sensing–mediated violacein production by Chromobacterium violaceum CV12472 at MIC and sub-MIC and showed percentage inhibition varying from 100% at MIC to 5.7% ± 0.2% at MIC/32. Against Chromobacterium violaceum CV026, BHBANA exhibited anti-quorum-sensing zone diameters of 10.5 ± 0.3 mm and 7.0 ± 0.1 mm at MIC and MIC/2, respectively. BHBANA shows concentration-dependent inhibition of swarming motility on flagellated Pseudomonas aeruginosa PA01 with the highest % inhibition of 28.30% ± 0.50% μg mL−1 at MIC. The product inhibits biofilm formation, with the best biofilm inhibition being observed against Staphylococcus aureus varying from 72.24% ± 0.86% (MIC) to 09.82% ± 0.10% (MIC/8). Molecular docking studies carried out utilizing the Schrodinger software identified interactions between BHBANA and different receptor compartments of Chromobacterium violaceum, which can block pathogenic gene expression. The results suggest the potential of BHBANA in reducing microbial virulence.

Isolation and Quantification of 2-O-Caffeoyl-hydroxycitric Acid, an Active Component in Hot Water Extracts of Coriander (Coriandrum sativum L.), Which Inhibits Degranulation of RBL-2H3 Cells

Objectives: Natural compounds that can effectively prevent and alleviate allergic symptoms, such as hay fever, are widely sought after from sources such as natural ingredients that can be ingested daily. Coriander extracts have been reported to show anti-allergic activity; however, hot water extracts have not been tested previously. Here, we found that a hot water extract of the aerial parts of coriander inhibited the degranulation of rat basophilic leukemia cell line RBL-2H3 cells and identified the active compounds. Methods: Chromatographic methods were used to isolate compounds from the hot water extract of coriander. The chemical structures were elucidated by analyses of high-resolution electrospray ionization mass spectrum and nuclear magnetic resonance spectral data. The degranulation activity of compounds was evaluated using the β-hexosaminidase release assay. Results: We analyzed the components to identify active compounds. 2 S,3 S-2- O-caffeoyl-hydroxycitric acid (1), and 2- O-caffeoyl-hydroxycitric acid 6′- O-methyl ester (2) were isolated from the hot water extract of coriander, and both compounds showed degranulation inhibitory activity in RBL-2H3 cells at a concentration below 2.5 mM. The content of compound 1 in the freeze-dried coriander powder was calculated to be 2.0% via HPLC quantification. Conclusions: Compound 1 was considered to be the primary active contributor in the hot water extract of coriander.

Progressive Feedback Residual Attention Network for Cardiac Magnetic Resonance Imaging Super-Resolution.

Atrial fibrillation (AF) is an increasing medical burden worldwide, and its pathological manifestations are atrial tissue remodeling and low-pressure atrial tissue fibrosis. Due to the inherent defects of medical image data acquisition systems, the acquisition of high-resolution cardiac magnetic resonance imaging (CMRI) faces many problems. In response to these problems, we propose the Progressive Feedback Residual Attention Network (PFRN) for CMRI super-resolution. Specifically, we directly perform feature extraction on low-resolution images, retain feature information to a large extent, and then build multiple independent progressive feedback modules to extract high-frequency details. To accelerate network convergence and improve image reconstruction quality, we implement the MS-SSIM-L1 loss function. Furthermore, we utilize the residual attention stack module to explore the image's internal relevance and extract the low-resolution image's detailed features. Extensive benchmark evaluation shows that PFRN can improve the detailed information of the image SR reconstruction results, and the reconstructed CMRI has a better visual effect.

Calcification circumference, area, and location are associated with carotid stent expansion rate: high-resolution magnetic resonance vessel wall imaging study.

The plaque imaging findings associated with the stent expansion rate (SER) of the carotid artery are not well known. The purpose of this study was to investigate the imaging findings associated with SER. It was a retrospective investigation. Based on the kind of carotid stents used, retrospective data from 89 patients who had carotid artery stenting (CAS) for atherosclerotic carotid stenosis were gathered and divided into two groups: open-cell stents and closed-cell stents. Patients underwent preoperative carotid high-resolution magnetic resonance vessel wall imaging (HR-VWI). Use HR-VWI to quantitatively evaluate carotid wall thickness and plaque components. Calculate SER using digital subtraction angiography (DSA). All patients' baseline and HR-VWI imaging features were retrospectively analyzed. Simple and multivariable linear regression analysis was used to determine the imaging findings associated with SER of open-cell and closed-cell stents. A total of 89 patients (mean age, 70±8 years; 69 men) were included in the final analysis. Among 89 patients, 35 patients were treated with open-cell stents. Fifty-four patients were treated with closed-cell stents. In the open-cell stents group, the Maximum single-slice calcification circumference score, maximum wall thickness (WTmax), and total calcification location score with P<0.10 in the simple linear regression analysis were included in the multivariable linear regression analysis. The results of the multivariable linear regression revealed that only the Maximum single-slice calcification circumference score (β=-9.35; 95% CI: -18.15 to -0.56; P=0.03) was associated with SER of open-cell stents. In the closed-cell stents group, the Maximum single-slice calcification circumference score, WTmax, maximum area percentage of calcification, calcification volume, and total calcification location score with P<0.10 in the simple linear regression analysis were included in the multivariable linear regression analysis. The results of the multivariable linear regression revealed that the Maximum area percentage of calcification (β=-0.67; 95% CI: -1.29 to -0.05; P=0.03), Maximum single-slice calcification circumference score (β=-8.43; 95% CI: -13.36 to -3.49; P=0.001) and total calcification location score (β=-0.37; 95% CI: -1.08 to 0.09; P=0.02) were associated with SER of closed-cell stents. Calcified plaques are associated with SER of the carotid artery. Calcification circumference correlates with SER of open-cell stents. Calcification circumference, calcification area, and calcification location are related to SER of closed-cell stents, which may provide a new consideration for clinicians when choosing carotid artery stents.

A unified hybrid transformer for joint MRI sequences super-resolution and missing data imputation

Objective. High-resolution multi-modal magnetic resonance imaging (MRI) is crucial in clinical practice for accurate diagnosis and treatment. However, challenges such as budget constraints, potential contrast agent deposition, and image corruption often limit the acquisition of multiple sequences from a single patient. Therefore, the development of novel methods to reconstruct under-sampled images and synthesize missing sequences is crucial for clinical and research applications. Approach. In this paper, we propose a unified hybrid framework called SIFormer, which utilizes any available low-resolution MRI contrast configurations to complete super-resolution (SR) of poor-quality MR images and impute missing sequences simultaneously in one forward process. SIFormer consists of a hybrid generator and a convolution-based discriminator. The generator incorporates two key blocks. First, the dual branch attention block combines the long-range dependency building capability of the transformer with the high-frequency local information capture capability of the convolutional neural network in a channel-wise split manner. Second, we introduce a learnable gating adaptation multi-layer perception in the feed-forward block to optimize information transmission efficiently. Main results. Comparative evaluations against six state-of-the-art methods demonstrate that SIFormer achieves enhanced quantitative performance and produces more visually pleasing results for image SR and synthesis tasks across multiple datasets. Significance. Extensive experiments conducted on multi-center multi-contrast MRI datasets, including both healthy individuals and brain tumor patients, highlight the potential of our proposed method to serve as a valuable supplement to MRI sequence acquisition in clinical and research settings.

White Matter Metabolite Ratios Predict Cognitive Outcome in Pediatric Traumatic Brain Injury.

The prognostic ability of global white matter and gray matter metabolite ratios following pediatric traumatic brain injury (TBI) and their relationship to 12-month neuropsychological assessments of intelligence quotient (IQ), attention, and memory is presented. Three-dimensional proton magnetic resonance spectroscopic imaging (MRSI) in pediatric subjects with complicated mild (cMild), moderate, and severe TBI was acquired acutely (6-18 days) and 12 months post-injury and compared to age-matched typically developing adolescents. A global linear regression model, co-registering MRSI metabolite maps with 3D high-resolution magnetic resonance images, was used to identify longitudinal white matter and gray matter metabolite ratio changes. Acutely, gray matter NAA/Cr, white matter NAA/Cr, and white matter NAA/Cho ratios were significantly lower in TBI groups compared to controls. Gray matter NAA/Cho was reduced only in the severe TBI group. At 12 months, all metabolite ratios normalized to control levels in each of the TBI groups. Acute gray matter and white matter NAA ratios were significantly correlated to 12-month assessments of IQ, attention, and memory. These findings suggest that whole brain gray matter and white matter metabolite ratios reflect longitudinal changes in neuronal metabolism following TBI, which can be used to predict neuropsychological outcomes in pediatric subjects.

1H-NMR analysis of fluoroquinolone (pyridopyrrole quinoxaline, PPQ) conjugated to gold nanoparticles for synergistic anticancer drug design

The tethering mechanism between Pyrido Pyrrole Quinoxaline (PPQ) anticancer agent and gold nanoparticles (AuNPs) to form the PPQ/AuNPs complex as a promising anticancer reagent was investigated. Physicochemical properties, including viscosity, self-diffusion coefficients, and local molecular dynamics, of both PPQ and the PPQ/AuNPs complex were systematically examined using advanced techniques such as high-resolution 1H Nuclear Magnetic Resonance (1H-NMR), spin-lattice relaxation time (T1), and self-diffusion coefficient (D) analysis. Various PPQ/AuNPs systems were prepared and analyzed, encompassing concentrations of 0, 1.5, 4, 6.5, 8.3, 10.15, and 11.15 mg of PPQ. The results of T1demonstrated that the predominant intermolecular bonding occurs between AuNPs and fluorine atoms, particularly involving the neighboring proton to the fluorine and nitrogen atoms. Remarkably, the curve of self-diffusion coefficients displayed notable peaks at PPQ concentrations of approximately 4 mg and 8.3 mg. The interaction between PPQ molecules and AuNPs revealed a pronounced affinity for the fluorine sites and hydrogen atoms within the hydroxyl group of PPQ molecules when dissolved in aqueous solutions.

Diagnosis and differential diagnosis of tertiary androgenetic alopecia with severe alopecia areata based on high-resolution MRI.

No previous study investigated the anatomical changes of the scalp and hair follicles between tertiary androgenetic alopecia and severe alopecia areata using high-resolution magnetic resonance imaging (HR-MRI). This study aimed to explore the value of HR-MRI in assessing alopecia. Forty-eight people were included in this study. The imaging indicators of the vertex and occipital scalp were recorded and compared. The logistic regression model was developed for the indicators that differed between tertiary androgenetic alopecia and severe alopecia areata. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic efficacy of the model for tertiary androgenetic alopecia and severe alopecia areata. At the vertex, the thickness of the subcutaneous tissue layer, follicle depth, relative follicle depth, total number of follicles within a 2-cm distance, and number of strands reaching the middle and upper third of the subcutaneous fat layer within a 2-cm distance were statistically different between patients with tertiary androgenetic alopecia, those with severe alopecia areata, and healthy volunteers (p < 0.05). The logistic regression model suggested that the subcutaneous tissue layer thickness was important in discriminating tertiary androgenetic alopecia from severe alopecia areata. The ROC curve showed that the area under the curve, sensitivity, specificity, and best cutoff values of the subcutaneous tissue layer were 0.886, 94.4%, 70%, and 4.31 mm, respectively. HR-MRI can observe the changes in anatomical structures of the scalp and hair follicles in patients with alopecia. HR-MRI can be applied to the differential diagnosis of tertiary androgenetic alopecia and severe alopecia areata.

Liquid-liquid chromatography isolation of Petasites hybridus sesquiterpenes and their LC-HR-MS/MS and NMR characterization

Petasites hybridus L. (butterbur, Asteraceae) is a well-known medicinal plant traditionally used as a remedy for neurological, respiratory, cardiovascular, and gastrointestinal disorders. Eremophilane-type sesquiterpenes (petasins) are considered to be the major bioactive constituents of butterbur. However, efficient methods to isolate high-purity petasins in sufficient amounts for further analytical and biological testing are lacking. In this study, various sesquiterpenes were separated from a methanol rootstock extract of P. hybridus with liquid-liquid chromatography (LLC). The appropriate biphasic solvent system was selected using the predictive thermodynamic model COSMO-RS and shake-flask experiments. After the selection of the feed (extract) concentration and operating flow rate, a batch LLC experiment was performed with n-hexane/ethyl acetate/methanol/water 5/1/5/1 (v/v/v/v). For those LLC fractions containing petasin derivatives with purities < 95%, a preparative high-performance liquid chromatography purification step followed. All isolated compounds were identified by state-of-the-art spectroscopic methods, i.e., liquid chromatography coupled with high-resolution tandem mass spectrometry and nuclear magnetic resonance techniques. As a result, six compounds were obtained, namely 8β-hydroxyeremophil-7(11)-en-12,8-olide, 2-[(angeloyl)oxy]eremophil-7(11)-en-12,8-olide, 8α/β-H-eremophil-7(11)-en-12,8-olide, neopetasin, petasin, and isopetasin. The isolated petasins can be further used as reference materials for standardization and pharmacological evaluation.

High-Resolution Magic Angle Spinning (HRMAS) NMR Identifies Oxidative Stress and Impairment of Energy Metabolism by Zearalenone in Embryonic Stages of Zebrafish (Danio rerio), Olive Flounder (Paralichthys olivaceus) and Yellowtail Snapper (Ocyurus chrysurus).

Zearalenone (ZEA) is a mycotoxin, commonly found in agricultural products, linked to adverse health impacts in humans and livestock. However, less is known regarding effects on fish as both ecological receptors and economically relevant "receptors" through contamination of aquaculture feeds. In the present study, a metabolomics approach utilizing high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) was applied to intact embryos of zebrafish (Danio rerio), and two marine fish species, olive flounder (Paralichthys olivaceus) and yellowtail snapper (Ocyurus chrysurus), to investigate the biochemical pathways altered by ZEA exposure. Following the assessment of embryotoxicity, metabolic profiling of embryos exposed to sub-lethal concentrations showed significant overlap between the three species and, specifically, identified metabolites linked to hepatocytes, oxidative stress, membrane disruption, mitochondrial dysfunction, and impaired energy metabolism. These findings were further supported by analyses of tissue-specific production of reactive oxygen species (ROS) and lipidomics profiling and enabled an integrated model of ZEA toxicity in the early life stages of marine and freshwater fish species. The metabolic pathways and targets identified may, furthermore, serve as potential biomarkers for monitoring ZEA exposure and effects in fish in relation to ecotoxicology and aquaculture.

Identification, isolation, and structural characterization of novel forced degradation products of Ertugliflozin using advanced analytical techniques

The research elucidates the stress degradation behavior of Ertugliflozin, which is used for the treatment of type-2 diabetics. The degradation was conducted as per ICH guidelines and Ertugliflozin is relatively stable in thermal, photolytic, neutral, and alkaline hydrolysis conditions; however, considerable degradation was detected in acid hydrolysis and oxidative hydrolysis. Degradation products were identified by ultra-high-performance liquid chromatography-mass spectrometry, isolated by semi-preparative high-performance liquid chromatography, and structural characterization using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Total four degradation products were identified and isolated in acid degradation, which are degradation products 1, 2, 3, and 4. Whereas in oxidative conditions, degradation product 5 was identified. All the five degradation products formed are novel, which was not reported earlier. This is the first time documented complete structural characterization of all five degradation products by using a hyphenated analytical technique. High-resolution mass, and nuclear magnetic resonance spectroscopy were used in the present study to get concrete confirmation of degradation products structures. The current method is also used to identify degradation products with shorter runtime in the future.

Incremental value of enhanced plaque length for identifying intracranial atherosclerotic culprit plaques: a high-resolution magnetic resonance imaging study

ObjectivesBesides plaque enhancement grade, the incremental value of enhancement-related high-resolution MRI features in defining culprit plaques needs further evaluation. This study was focused on assessing whether plaque enhancement features contribute to culprit plaque identification and further risk stratification.MethodsWe retrospectively studied patients who experienced an acute ischaemic stroke and transient ischaemic attack due to intracranial atherosclerosis from 2016 to 2022. The enhancement features included enhancement grade, enhanced length, and enhancement quadrant. Associations between plaque enhancement features and culprit plaques, as well as diagnostic value, were investigated using logistic regression and receiver operating characteristic analyses.ResultsOverall, 287 plaques were identified, of which 231 (80.5%) and 56 (19.5%) were classified as culprit and non-culprit plaques, respectively. Comparison of the pre- and post-enhancement images revealed enhanced length longer than the plaque length in 46.32% of the culprit plaques. Multivariate logistic regression showed that enhanced length longer than plaque length (OR 6.77; 95% CI 2.47–18.51) and grade II enhancement (OR 7.00; 95% CI 1.69–28.93) were independently associated with culprit plaques. The area under the curve value for the combination of stenosis and plaque enhancement grade for the diagnosis of culprit plaques was 0.787, which increased significantly to 0.825 on the addition of enhanced length longer than the plaque length (p = 0.026 for DeLong’s test).ConclusionsEnhanced length longer than the plaque length and grade II enhancement were independently associated with culprit plaques. The combination of the enhanced plaque features resulted in better culprit plaque identification.