Advances in functional studies of plant MYC transcription factors.

Myelocytomatosis (MYC) transcription factors (TFs) belong to the basic helix-loop-helix (bHLH) family in plants and play a central role in governing a wide range of physiological processes. These processes encompass plant growth, development, adaptation to biotic and abiotic stresses, as well as secondary metabolism. In recent decades, significant strides have been made in comprehending the multifaceted regulatory functions of MYCs. This advancement has been achieved through the cloning of MYCs and the characterization of plants with MYC deficiencies or overexpression, employing comprehensive genome-wide 'omics' and protein-protein interaction technologies. MYCs act as pivotal components in integrating signals from various phytohormones' transcriptional regulators to orchestrate genome-wide transcriptional reprogramming. In this review, we have compiled current research on the role of MYCs as molecular switches that modulate signal transduction pathways mediated by phytohormones and phytochromes. This comprehensive overview allows us to address lingering questions regarding the interplay of signals in response to environmental cues and developmental shift. It also sheds light on the potential implications for enhancing plant resistance to diverse biotic and abiotic stresses through genetic improvements achieved by plant breeding and synthetic biology efforts.

Quantitative morphometric changes in vascular mild cognitive impairment patients: early diagnosis of dementia.

Vascular mild cognitive impairment (VMCI) is an early and reversible stage of dementia. Volume differences in regional gray matter may reveal the development and prognosis of VMCI. This study selected 2 of the most common types of VMCI, namely, periventricular white matter hyperintensities (PWMH, n = 14) and strategic single infarctions (SSI, n = 10), and used the voxel-based morphometry method to quantify their morphological characteristics. Meanwhile, age- and sex-matched healthy volunteers were included (n = 16). All the participants were neuropsychologically tested to characterize their cognitive function and underwent whole-brain magnetic resonance imaging scanning. Our results showed that the volumes of the bilateral temporal lobes and bilateral frontal gray matter were obviously diminished in the PWMH group. The atrophy volume difference was 4,086 voxels in the left temporal lobe, 4,154 voxels in the right temporal lobe, 1,718 voxels in the left frontal lobe, and 1,141 voxels in the right frontal lobe (P ≤ 0.001). Moreover, the characteristics of the gray matter atrophy associated with the PWMH were more similar to those associated with Alzheimer's disease than SSI, which further revealed the susceptibility for escalation from PWMH to dementia. In conclusion, PWMH patients and SSI patients have different morphological characteristics, which explain the different prognoses of VMCI.

Characterization of Temperature and Strain Changes in Lithium-Ion Batteries Based on a Hinged Differential Lever Sensitization Fiber Bragg Grating Strain-Temperature Simultaneous-Measurement Sensor.

Li-ion batteries are expected to become the mainstream devices for green energy storage or power supply in the future due to their advantages of high energy and power density and long cycle life. Monitoring the temperature and strain change characteristics of Li-ion batteries during operation is conducive to judging their safety performance. The hinged differential lever sensitization structure was used for strain sensitization in the design of an FBG sensor, which also allowed the simultaneous measurement of strain and temperature. The temperature and strain variation characteristics on the surface of a Li-ion soft-packed battery were measured using the des.igned sensor. This report found that the charging and discharging processes of Li-ion batteries are both exothermic processes, and exothermic heat release is greater when discharging than when charging. The strain on the surface of Li-ion batteries depends on electrochemical changes and thermal expansion effects during the charge and discharge processes. The charging process showed an increasing strain, and the discharging process showed a decreasing strain. Thermal expansion was found to be the primary cause of strain at high rates.

Surface Microstructure Study on Corona Discharge-Treated Polyethylene Using Positron Annihilation Spectroscopy.

The microstructure and chemical properties of the corona discharge process could provide an effective method for predicting the performance of high-voltage cable insulation materials. In this work, the depth profile of the microstructure and chemical characteristics of corona discharge-treated PE were extensively investigated using Doppler broadening of position annihilation spectroscopy accompanied with positron annihilation lifetime spectroscopy, attenuated total reflectance Fourier transform infrared spectra, Raman spectra and contact angle measurement. By increasing corona discharge duration, the oxygen-containing polar groups, including hydroxyl, carbonyl and ester groups, strongly contribute to the deterioration of hydrophobicity and the enhancement of hydrophilicity. And the mean free volume size, with a broadening distribution, decreases slightly. The line shape S parameter decreases because of the decrease in free volume elements and the appearance of oxygen-containing groups. Also, the thickness of the degradation layer, determined from the S parameter with positron injection depth, increases and diffuses into the PE matrix. A linear S-W plot within the degradation layer of different corona treatment duration samples indicates the defect type does not change. The S parameter decreases and the W parameter increases with an increasing corona duration. Using a slow positron beam, the nondestructive probe can be used to profile the microstructure and chemical environment across the corona discharge damage depth, which is beneficial for investigating the surface and interfacial insulation materials.

The value of different involvement patterns of the knee "synovio-entheseal complex" in the differential diagnosis of spondyloarthritis, rheumatoid arthritis, and osteoarthritis: an MRI-based study.

OBJECTIVES: To explore the different involvement patterns of the knee "synovio-entheseal complex (SEC)" on MRI in patients with spondyloarthritis (SPA), rheumatoid arthritis (RA), and osteoarthritis (OA). METHODS: This study retrospectively included 120 patients (male:female, 55:65) with a mean age of 39.20 years diagnosed with SPA (n = 40), RA (n = 40), and OA (n = 40) at the First Central Hospital of Tianjin between January 2020 and May 2022. Six knee entheses were assessed by two musculoskeletal radiologists according to the SEC definition. Bone marrow lesions associated with entheses include bone marrow edema (BME) and bone erosion (BE), which were classified as entheseal or peri-entheseal based on their relationship to the entheses. Three groups (OA, RA, and SPA) were established to characterize the location of enthesitis and the different SEC involvement patterns. Inter-group and intra-group differences were analyzed using the ANOVA or chi-square tests, and the inter-class correlation coefficient (ICC) test was used to determine inter-reader agreement. RESULTS: The study contained a total of 720 entheses. The SEC-based analysis revealed different involvement patterns in three groups. The OA group had the most abnormal signals in tendons/ligaments (p = 0.002). The RA group had considerably greater synovitis (p = 0.002). The majority of peri-entheseal BE was identified in the OA and RA groups (p = 0.003). Furthermore, entheseal BME in the SPA group was significantly different from those in the other two groups (p < 0.001). CONCLUSIONS: SEC involvement patterns differed in SPA, RA, and OA, which is important for differential diagnosis. SEC should be used as a whole evaluation method in clinical practice. KEY POINTS: • The "synovio-entheseal complex (SEC)" explained differences and characteristic alterations in the knee joint in patients with spondyloarthritis (SPA), rheumatoid arthritis (RA), and osteoarthritis (OA). • The various SEC involvement patterns are crucial for differentiating SPA, RA, and OA. • When "knee pain" is the only symptom, a detailed identification of characteristic alterations in the knee joint of SPA patients may help timely treatment and delay the structural damage.

Radiomics nomogram for the prediction of microvascular invasion of HCC and patients' benefit from postoperative adjuvant TACE: a multi-center study.

OBJECTIVES: To evaluate the performance of a radiomics nomogram developed based on gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) MRI for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS: A total of 260 eligible patients were retrospectively enrolled from three hospitals (140, 65, and 55 in training, standardized external, and non-standardized external validation cohort). Radiomics features and image characteristics were extracted from Gd-EOB-DTPA MRI image before hepatectomy for each lesion. In the training cohort, a radiomics nomogram which incorporated the radiomics signature and radiological predictors was developed. The performance of the radiomics nomogram was assessed with respect to discrimination calibration, and clinical usefulness with external validation. A score (m-score) was constructed to stratify the patients and explored whether it could accurately predict patient who benefit from PA-TACE. RESULTS: A radiomics nomogram integrated with the radiomics signature, max-D(iameter) > 5.1 cm, peritumoral low intensity (PTLI), incomplete capsule, and irregular morphology had favorable discrimination in the training cohort (AUC = 0.982), the standardized external validation cohort (AUC = 0.969), and the non-standardized external validation cohort (AUC = 0.981). Decision curve analysis confirmed the clinical usefulness of the novel radiomics nomogram. The log-rank test revealed that PA-TACE significantly decreased the early recurrence in the high-risk group (p = 0.006) with no significant effect in the low-risk group (p = 0.270). CONCLUSIONS: The novel radiomics nomogram combining the radiomics signature and clinical radiological features achieved preoperative non-invasive MVI risk prediction and patient benefit assessment after PA-TACE, which may help clinicians implement more appropriate interventions. CLINICAL RELEVANCE STATEMENT: Our radiomics nomogram could represent a novel biomarker to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization, which may help clinicians to implement more appropriate interventions and perform individualized precision therapies. KEY POINTS: • The novel radiomics nomogram developed based on Gd-EOB-DTPA MRI achieved preoperative non-invasive MVI risk prediction. • An m-score based on the radiomics nomogram could stratify HCC patients and further identify individuals who may benefit from the PA-TACE. • The radiomics nomogram could help clinicians to implement more appropriate interventions and perform individualized precision therapies.

Pressure effect on the magnetism and crystal structure of magnetoelectric metal-organic framework [CH3NH3][Co(HCOO)3].

[CH3NH3][Co(HCOO)3] is the first perovskite-like metal-organic framework exhibiting spin-driven magnetoelectric effects. However, the high-pressure tuning effects on the magnetic properties and crystal structure of [CH3NH3][Co(HCOO)3] have not been studied. In this work, alongside ac magnetic susceptibility measurements, we investigate the magnetic transition temperature evolution under high pressure. Upon increasing the pressure from atmospheric pressure to 0.5 GPa, TN (15.2 K) remains almost unchanged. Continuing to compress the sample results in TN gradually decreasing to 14.8 K at 1.5 GPa. This may be due to pressure induced changes in the bond distance and bond angle of the O-C-O superexchange pathway. In addition, by using high pressure powder X-ray diffraction and Raman spectroscopy, we conducted in-depth research on the pressure dependence of the lattice parameters and Raman modes of [CH3NH3][Co(HCOO)3]. The increase in pressure gives rise to a phase transition from the orthorhombic Pnma to a monoclinic phase at approximately 6.13 GPa. Our study indicates that high pressure can profoundly alter the crystal structure and magnetic properties of perovskite type MOF materials, which could inspire new endeavors in exploring novel phenomena in compressed metal-organic frameworks.

More accurate prediction of treatment response than mean apparent diffusion coefficient value in multiple myeloma using whole body MRI histogram analysis.

Aim: To assess baseline histogram parameters from apparent diffusion coefficient (ADC) images in predicting early treatment response in newly diagnosed multiple myeloma (NDMM) patients. Methods: The histogram parameters of lesions in 68 NDMM patients were obtained with the Firevoxel software. The presence of deep response after two cycles of induction was recorded. Results: Some parameters were significantly different between the two groups, for example, ADC 75% in lumbar spine (p = 0.026). No significant difference in mean ADC for any anatomic site was found (all p > 0.05). The combination of ADC 75, ADC 90 and ADC 95% in lumbar spine; ADC skewness and ADC kurtosis in rib achieved a sensitivity of 100% in predicting deep response. Conclusion: Histogram analysis of ADC images can describe NDMM heterogeneity and accurately predict treatment response.

Global development and future trends of artificial sweetener research based on bibliometrics.

Artificial sweeteners have sparked a heated debate worldwide due to their ambiguous impacts on public and environmental health and food safety and quality. Many studies on artificial sweeteners have been conducted; however, none scientometric studies exist in the field. This study aimed to elaborate on the knowledge creation and development of the field of artificial sweeteners and predict the frontiers of knowledge based on bibliometrics. In particular, this study combined VOSviewer, CiteSpace, and Bibliometrix to visualize the mapping of knowledge production, covered 2389 relevant scientific publications (1945-2022), and systematically analyzed articles and reviews (n = 2101). Scientific publications on artificial sweeteners have been growing at an annual rate of 6.28% and globally attracting 7979 contributors. Susan J. Brown with total publications (TP) of 17, average citation per article (AC) of 36.59, and Hirsch (h)-index of 12 and Robert F. Margolskee (TP = 12; AC = 2046; h-index = 11) were the most influential scholars. This field was clustered into four groups: eco-environment and toxicology, physicochemical mechanisms, public health and risks, and nutrition metabolism. The publications about environmental issues, in particular, "surface water," were most intensive during the last five years (2018-2022). Artificial sweeteners are gaining importance in the monitoring and assessment of environmental and public health. Results of the dual-map overlay showed that the future research frontiers tilt toward molecular biology, immunology, veterinary and animal sciences, and medicine. Findings of this study are conducive to identifying knowledge gaps and future research directions for scholars.

Prediction of microvascular invasion in HCC by a scoring model combining Gd-EOB-DTPA MRI and biochemical indicators.

OBJECTIVES: This study aimed to establish a reliable diagnostic scoring model for the preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and biochemical indicators. METHODS: This retrospective study included 129 patients with HCC at our hospital from 2014 to 2020. Based on the intratumoral and peritumoral features on Gd-EOB-DTPA MRI and biochemical indicators, a scoring model was developed for preoperative prediction of MVI, and examined for diagnostic efficacy according to postoperative pathological results. The scoring model was further externally validated in an independent cohort of 63 HCC patients. RESULTS: Logistic regression analysis was performed to identify five parameters related to MVI, including maximum tumor diameter, peritumoral low intensity in the hepatobiliary phase, incomplete capsule, apparent diffusion coefficient (ADC), and [alkaline phosphatase (ALP) (U/L) + gamma-glutamyl transpeptidase (GGT) (U/L)] / lymphocyte count (× 109/L) ratio (AGLR). Based on these five parameters, a scoring model was developed, and the accuracy, sensitivity, specificity, PPV, and NPV in predicting MVI were 93.6%, 94.7%, 93.2%, 85.7%, and 97.6%, respectively, with a score > 8 set as the threshold. CONCLUSION: The scoring model based on Gd-EOB-DTPA MRI and biochemical indicators provides a reliable tool for preoperative prediction of MVI in HCC patients. KEY POINTS: • The scoring model based on Gd-EOB-DTPA MRI and biochemical indicators is practical for preoperative prediction of MVI in HCC patients. • AGLR is an independent risk factor for MVI. • The scoring model could help implement more appropriate interventions, potentially leading to precise and individualized treatments based on the biological characteristics of the tumor.

CT-based radiomics signature analysis for evaluation of response to induction chemotherapy and progression-free survival in locally advanced hypopharyngeal carcinoma.

OBJECTIVES: To establish and validate a CT radiomics model for prediction of induction chemotherapy (IC) response and progression-free survival (PFS) among patients with locally advanced hypopharyngeal carcinoma (LAHC). METHODS: One hundred twelve patients with LAHC (78 in training cohort and 34 in validation cohort) who underwent contrast-enhanced CT (CECT) scans prior to IC were enrolled. Least absolute shrinkage and selection operator (LASSO) was used to select the crucial radiomic features in the training cohort. Radiomics signature and clinical data were used to build a radiomics nomogram to predict individual response to IC. Kaplan-Meier analysis and log-rank test were used to evaluate ability of radiomics signature in progression-free survival risk stratification. RESULTS: The radiomics signature consisted of 6 selected features from the arterial and venous phases of CECT images and demonstrated good performance in predicting the IC response in both two cohorts. The radiomics nomogram showed good discriminative performance, and the C-index of nomogram was 0.899 (95% confidence interval (CI), 0.831-0.967) and 0.775 (95% CI, 0.591-0.959) in the training and validation cohorts, respectively. Survival analysis indicated that low-risk and high-risk groups defined by the value of radiomics signature had significant difference in PFS (3-year PFS 66.4% vs 29.7%, p < 0.001). CONCLUSIONS: Multiparametric CT-based radiomics model could be useful for predicting treatment response and PFS in patients with LAHC who underwent IC. KEY POINTS: • CT radiomics can predict IC response and progression-free survival in hypopharyngeal carcinoma. • We combined significant radiomics signature with clinical predictors to establish a nomogram to predict individual response to IC. • Radiomics signature could divide patients into the high-risk and low-risk groups based on the PFS.

Prediction of Early Treatment Response in Multiple Myeloma Using MY-RADS Total Burden Score, ADC, and Fat Fraction From Whole-Body MRI: Impact of Anemia on Predictive Performance.

BACKGROUND. The recently released Myeloma Response Assessment and Diagnosis System (MY-RADS) for multiple myeloma (MM) evaluation using whole-body MRI (WB-MRI) describes the total burden score. However, assessment is confounded by red bone marrow hyperplasia in anemia. OBJECTIVE. The purpose of this study is to assess the utility of the MY-RADS total burden score, ADC, and fat fraction (FF) from WB-MRI in predicting early treatment response in patients with newly diagnosed MM and to compare the utility of these measures between patients with and without anemia. METHODS. This retrospective study included 56 patients (40 men, 16 women; mean age, 57.4 ± 9.6 [SD] years) with newly diagnosed MM who underwent baseline WB-MRI including DWI and modified Dixon sequences. Two radiologists recorded total burden score using MY-RADS and measured the ADC and FF of diffuse and focal disease sites. Mean values across sites were derived. Interobserver agreement was evaluated, and the mean assessments of the readers were used for further analyses. Presence of deep response after four cycles of induction chemotherapy was recorded. Patients were classified as having anemia if their hemoglobin level was less than 100 g/L. The utility of WBMRI parameters in predicting deep response was assessed. RESULTS. A total of 24 of 56 patients showed deep response, and 25 of 56 patients had anemia. Interobserver agreement, which was expressed using intraclass correlation coefficients, ranged from 0.95 to 0.99. Among patients without anemia, those with deep response compared with those without deep response had a lower total burden score (9.0 vs 18.0), a lower ADC (0.79 × 10-3 mm2/s vs 1.08 × 10-3 mm2/s), and a higher FF (0.21 vs 0.10) (all p < .001). The combination of these three parameters (optimal cutoffs: ≤ 15 for total burden score, ≤ 0.84 × 10-3 mm2/s for ADC, and > 0.16 for FF) achieved sensitivity of 93.8%, specificity of 93.3%, and accuracy of 93.5% for predicting deep response. In patients with anemia, none of the three parameters were significantly different between patients with and without deep response (all p > .05), and the combination of parameters achieved sensitivity of 56.3%, specificity of 100.0%, and accuracy of 72.0%. CONCLUSION. Low total burden score, low ADC, and high FF from WB-MRI may predict deep response in patients with MM, although only among those without anemia. CLINICAL IMPACT. WB-MRI findings may help guide determination of prognosis and initial treatment selection in MM.

MiR-106a-5p modulates apoptosis and metabonomics changes by TGF-ß/Smad signaling pathway in cleft palate.

BACKGROUND: The molecular mechanisms of abnormal palatogenesis were investigated in this study. A key regulator, miR-106a-5p, and its target pathway were analyzed. OBJECTIVES: This research is trying to clarify the underlying mechanism of the modulation of miRNA transcription during the formation of cleft palate by 7T and 9.4T NMR metabolomic platforms. METHOD: Differentially expressed miRNAs and mRNAs were analyzed by microarray analysis and verified by qRT-PCR. The protein expression in TGFß signaling pathways were analyzed by Western Blotting. The relationship between miR-106a-5p and TGFß were analyzed by luciferase reporter assay. Cell apoptosis were analyzed by flow cytometer. And finally, the metabonomics were analyzed by NMR and multivariate data analysis models (MVDA). RESULTS: The expression of miR-106a-5p increased in cleft palatal tissue and negatively correlated with the protein level of Tgfbr2. The luciferase assay further proved that the tgfbr2 was a direct target of miR-106a-5p. In another aspect, miR-106a-5p increased apoptosis level in palatal mesenchymal cells, possibly because its inhibition of TGFß signaling pathway. Moreover, low cholesterol and choline levels with high citric acid and lipid levels were observed by 7T and 9.4T NMR metabonomic analysis, which inferred the disorder of cell membrane synthesis in cleft palate formation. Furthermore, transformation from choline to phosphatidylcholine regulated by miR-106a-5p was also disrupted, resulting in phosphatidic choline synthesis disorder and reduced cell membrane synthesis. CONCLUSIONS: The regulatory mechanism of cleft palate was studied at transcriptional and metabolomics levels, which may provide important information in understanding the primary cause of this abnormality.

Effects of Subthalamic Deep Brain Stimulation With Different Frequencies in a Parkinsonian Rat Model.

OBJECTIVE: Subthalamic deep brain stimulation (STN-DBS) could be an effective alternative treatment for patients with Parkinson's disease (PD). However, the mechanisms of deep brain stimulation (DBS) at different frequencies are still unclear. In this study, diffusion tensor imaging (DTI) was used to detect parameter changes in different regions of rat brains after DBS, and rat exercise capacity and brain tissue immunohistochemistry were evaluated. MATERIALS AND METHODS: The 6-hydroxydopamine-induced hemi-parkinsonian rat models were made and divided into four groups: a control group, sham group, low-frequency group, and high-frequency group. Low-frequency (30 Hz) and high-frequency (130 Hz) DBS were given to the STN in rats. First, an open-field experiment was used to evaluate changes in exercise performance. Then, the DTI was used to measure parameter changes in the substantia nigra (SN). Finally, immunohistochemistry was used to analyze the expression of tyrosine hydroxylase (TH), NeuN, and α-synuclein (α-syn) in the SN in the rats. RESULTS: There were significant differences in movement distance changes between the high-frequency stimulation (HFS) group and low-frequency stimulation (LFS) group, the HFS group and Ctrl group, and the Sham group and Ctrl group (all p < 0.05) after one week of stimulation. In the HFS group, the fractional anisotropy value of the SN was significantly higher than that of the other groups (p < 0.05), and the apparent diffusion coefficient and radial diffusion coefficient values were significantly lower than those of the other groups (p < 0.01). Immunohistochemical analysis showed that the integral optical density values of SN TH staining (p < 0.01) and NeuN staining (p < 0.05) in the HFS group were both significantly higher than those in the other groups. CONCLUSION: STN-HFS (130 Hz) and sham operation for one week can significantly improve the exercise performance of PD rats. The exercise performance of PD rats in LFS group (30 Hz) is worse compared with HFS group (130 Hz). HFS plays a role in neuroprotection and improvement of exercise performance of PD rats. Moreover, DTI can be used as an effective technique to assess the therapeutic effects and severity of PD.

Self-assembly of pentapeptides in ethanol to develop organogels.

Organogels have a wide variety of applications in the fields of chemistry, electricity, biomedicine and environmental engineering, which call for robust strategies for designing and developing novel organogelators. Here, we reported a pentapeptide, ECAYF, which was capable of forming a self-healing ethanol gel exhibiting viscoelastic and solid-like properties. The ethanol gel of ECAYF was stable for at least several months, suggesting strong non-covalent interactions between ethanol and the peptide in the gel. In the ethanol gel, self-assembled peptide fibrils were found to immobilize the ethanol molecules for gelation. Results also suggested that the EAF-5 peptide adopted H-bonding ß-sheet secondary structures, which further assembled into fibrils. Meanwhile, the self-assembly of the ECAYF peptide in mixtures of differently fractioned ethanol and H2O was observed, which clearly indicated that ethanol promoted the assembly of ECAYF in the solutions. These findings are helpful in understanding the roles of organic solvents as well as the complicated interactions between the solvent and gelator molecules in gelation.

N-Acetyl and Glutamatergic Neurometabolites in Perisylvian Brain Regions of Methamphetamine Users.

Background: Methamphetamine induces neuronal N-acetyl-aspartate synthesis in preclinical studies. In a preliminary human proton magnetic resonance spectroscopic imaging investigation, we also observed that N-acetyl-aspartate+N-acetyl-aspartyl-glutamate in right inferior frontal cortex correlated with years of heavy methamphetamine abuse. In the same brain region, glutamate+glutamine is lower in methamphetamine users than in controls and is negatively correlated with depression. N-acetyl and glutamatergic neurochemistries therefore merit further investigation in methamphetamine abuse and the associated mood symptoms. Methods: Magnetic resonance spectroscopic imaging was used to measure N-acetyl-aspartate+N-acetyl-aspartyl-glutamate and glutamate+glutamine in bilateral inferior frontal cortex and insula, a neighboring perisylvian region affected by methamphetamine, of 45 abstinent methamphetamine-dependent and 45 healthy control participants. Regional neurometabolite levels were tested for group differences and associations with duration of heavy methamphetamine use, depressive symptoms, and state anxiety. Results: In right inferior frontal cortex, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate correlated with years of heavy methamphetamine use (r = +0.45); glutamate+glutamine was lower in methamphetamine users than in controls (9.3%) and correlated negatively with depressive symptoms (r = -0.44). In left insula, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate was 9.1% higher in methamphetamine users than controls. In right insula, glutamate+glutamine was 12.3% lower in methamphetamine users than controls and correlated negatively with depressive symptoms (r = -0.51) and state anxiety (r = -0.47). Conclusions: The inferior frontal cortex and insula show methamphetamine-related abnormalities, consistent with prior observations of increased cortical N-acetyl-aspartate in methamphetamine-exposed animal models and associations between cortical glutamate and mood in human methamphetamine users.

Microstructural and Neurochemical Changes in the Rat Brain After Diffuse Axonal Injury.

BACKGROUND: Diffuse axonal injury (DAI) is one of the devastating types of traumatic brain injury, but is difficult to detect on conventional imaging in its early stages. PURPOSE: To test the technical feasibility and diagnostic value of diffusion kurtosis imaging (DKI) and glutamate chemical exchange saturation transfer (GluCEST) imaging in the brain after DAI. STUDY TYPE: Prospective. ANIMAL MODEL: Sixty Sprague-Dawley rats. The DAI model was induced by using the impact acceleration model of Marmarou et al with modified settings. FIELD STRENGTH/SEQUENCE: A 7.0T animal MR scanner with a fast spin-echo sequence (T2 -weighted imaging), fast spin-echo multislice sequence (DKI), echo planar imaging in the signal of the chemical exchange saturation transfer sequence (CEST), and point-resolved spectroscopy sequence (hydrogenproton magnetic resonance spectroscopy, 1 H-MRS). ASSESSMENT: Brain MRI scanned before and 2 hours after injury. DKI images were processed with MatLab and MRIcro software, GluCEST images were processed using software routines written in MatLab, and spectroscopic data were postprocessed with LCModel. STATISTICAL TESTS: The parameters of these techniques were assessed using the independent sample t-test and Pearson correlation. RESULTS: Mean kurtosis and mean diffusivity values were significantly higher than controls in the parietal lobe, hippocampus, and thalamus (P < 0.01). However, fractional anisotropy was lower only in the parietal lobe, with no detectable changes in the hippocampus and thalamus. GluCEST values of the parietal lobe, hippocampus, and thalamus were significantly higher than controls in DAI rats (P < 0.01). This change was further validated through 1 H-MRS. A positive correlation was observed between glutamate (Glu) and glutamate compound (Glx) concentrations and GluCEST values (Glu: R2 = 0.589, Glx: R2 = 0.878). DATA CONCLUSION: DKI and GluCEST might be acceptably sensitive for tracking microstructural and neurochemical changes in the brain following DAI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1069-1077.

Quartz Disrupts Iron Homeostasis in Alveolar Macrophages To Impact a Pro-Inflammatory Effect.

The biological response of bronchial epithelial cells to particles is associated with a sequestration of cell metal by the particle surface and a subsequent disruption in host iron homeostasis. The macrophage is the cell type resident in the respiratory tract that is most likely to make initial contact with inhaled particles. We tested the postulates that (1) silica, a prototypical particle, disrupts iron homeostasis in alveolar macrophages (AMs); and (2) the altered iron homeostasis results in both an oxidative stress and pro-inflammatory effects. Human AMs (1.0 × 106/mL) demonstrated an increased import of iron following particle exposure with nonheme iron concentrations of 0.57 ± 0.03, 1.72 ± 0.09, 0.88 ± 0.09, and 3.21 ± 0.11 ppm in cells exposed for 4 h to media, 500 µM ferric ammonium citrate (FAC), 100 µg/mL silica, and both silica and FAC, respectively. Intracellular ferritin concentrations and iron release were similarly increased after AM exposure to FAC and silica. Silica increased oxidant generation by AMs measured using both dichlorofluorescein diacetate fluorescence and reduction of nitroblue tetrazolium salt. Concentrations of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α in macrophage supernatant increased following 100 µg/mL silica exposure for 24 h. Treatment of AMs with 500 µM FAC decreased both oxidant generation and cytokine release associated with silica exposure, supporting a dependence of these effects on sequestration of cell metal by the particle surface. We conclude that (1) silica exposure disrupts iron homeostasis resulting in increased import, accumulation, and release of the metal; and (2) the altered iron homeostasis following silica exposure impacts oxidant generation and pro-inflammatory effects.

Novel nanomedicine with a chemical-exchange saturation transfer effect for breast cancer treatment in vivo.

BACKGROUND: Nanomedicine is a promising new approach to cancer treatment that avoids the disadvantages of traditional chemotherapy and improves therapeutic indices. However, the lack of a real-time visualization imaging technology to monitor drug distribution greatly limits its clinical application. Image-tracked drug delivery is of great clinical interest; it is useful for identifying those patients for whom the therapy is more likely to be beneficial. This paper discusses a novel nanomedicine that displays features of nanoparticles and facilitates functional magnetic resonance imaging but is challenging to prepare. RESULTS: To achieve this goal, we synthesized an acylamino-containing amphiphilic block copolymer (polyethylene glycol-polyacrylamide-polyacetonitrile, PEG-b-P(AM-co-AN)) by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PEG-b-P(AM-co-AN) has chemical exchange saturation transfer (CEST) effects, which enable the use of CEST imaging for monitoring nanocarrier accumulation and providing molecular information of pathological tissues. Based on PEG-b-P(AM-co-AN), a new nanomedicine PEG-PAM-PAN@DOX was constructed by nano-precipitation. The self-assembling nature of PEG-PAM-PAN@DOX made the synthesis effective, straightforward, and biocompatible. In vitro studies demonstrate decreased cytotoxicity of PEG-PAM-PAN@DOX compared to free doxorubicin (half-maximal inhibitory concentration (IC50), mean ~ 0.62 µg/mL vs. ~ 5 µg/mL), and the nanomedicine more efficiently entered the cytoplasm and nucleus of cancer cells to kill them. Further, in vivo animal experiments showed that the nanomedicine developed was not only effective against breast cancer, but also displayed an excellent sensitive CEST effect for monitoring drug accumulation (at about 0.5 ppm) in tumor areas. The CEST signal of post-injection 2 h was significantly higher than that of pre-injection (2.17 ± 0.88% vs. 0. 09 ± 0.75%, p < 0.01). CONCLUSIONS: The nanomedicine with CEST imaging reflects the characterization of tumors and therapeutic functions has great potential medical applications.

Novel tyrosinase inhibitory peptide with free radical scavenging ability.

Tyrosinase is a key enzyme involved in melanin synthesis. Therefore, various tyrosinase inhibitors have been screened by researchers in recent years. In the present study, we discovered a novel tyrosinase inhibitor, a peptide ECGYF (named EF-5), with free radical scavenging ability. The effect of tyrosinase inhibition by EF-5 was stronger than that of arbutin and glutathione, when analyzed both in vitro (IC50: 0.46 mM) and in vivo. The UV-Vis absorption and circular dichroism spectroscopies indicated that EF-5 interacted with tyrosinase in a different way as that of glutathione. The results of molecular docking showed that the binding between EF-5 and tyrosinase was determined majorly by hydrogen bonds and hydrophobic interactions. EF-5 had also retained its ability to scavenge both hydroxyl and superoxide radicals in vitro and was found to be nontoxic to cells, as revealed by the MTT assay. These features suggested that the EF-5 peptide may serve as a safe and effective alternative as a tyrosinase inhibitor.