GLP-1 in the Hypothalamic Paraventricular Nucleus Promotes Sympathetic Activation and Hypertension.

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for diabetes treatment. The paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expressions were present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist exendin 9-39 (EX9-39) or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase (NOX) inhibitor apocynin, adenylyl cyclase (AC) inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVN microinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, AC, and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in the PVN increased sympathetic outflow and blood pressure via cAMP-PKA-mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contributes to sympathetic overactivity and hypertension.

Associations of MRI-Derived Glymphatic System Impairment With Global White Matter Damage and Cognitive Impairment in Mild Traumatic Brain Injury: A DTI-ALPS Study.

BACKGROUND: Assessing the glymphatic function using diffusion tensor image analysis along the perivascular space (DTI-ALPS) may be helpful for mild traumatic brain injury (mTBI) management. PURPOSE: To assess glymphatic function using DTI-ALPS and its associations with global white matter damage and cognitive impairment in mTBI. STUDY TYPE: Prospective. POPULATION: Thirty-four controls (44.1% female, mean age 49.2 years) and 58 mTBI subjects (43.1% female, mean age 48.7 years), including uncomplicated mTBI (N = 32) and complicated mTBI (N = 26). FIELD STRENGTH/SEQUENCE: 3-T, single-shot echo-planar imaging sequence. ASSESSMENT: Magnetic resonance imaging (MRI) was done within 1 month since injury. DTI-ALPS was performed to assess glymphatic function, and peak width of skeletonized mean diffusivity (PSMD) was used to assess global white matter damage. Cognitive tests included Auditory Verbal Learning Test and Digit Span Test (forward and backward). STATISTICAL TESTS: Neuroimaging findings comparisons were done between mTBI and control groups. Partial correlation and multivariable linear regression assessed the associations between DTI-ALPS, PSMD, and cognitive impairment. Mediation effects of PSMD on the relationship between DTI-ALPS and cognitive impairment were explored. P-value <0.05 was considered statistically significant, except for cognitive correlational analyses with a Bonferroni-corrected P-value set at 0.05/3 ≈ 0.017. RESULTS: mTBI showed lower DTI-ALPS and higher PSMD, especially in complicated mTBI. DTI-ALPS was significantly correlated with verbal memory (r = 0.566), attention abilities (r = 0.792), executive function (r = 0.618), and PSMD (r = -0.533). DTI-ALPS was associated with verbal memory (ß = 8.77, 95% confidence interval [CI] 5.00, 12.54), attention abilities (ß = 5.67, 95% CI 4.56, 6.97), executive function (ß = 2.34, 95% CI 1.49, 3.20), and PSMD (ß = -0.79, 95% CI -1.15, -0.43). PSMD mediated 46.29%, 20.46%, and 24.36% of the effects for the relationship between DTI-ALPS and verbal memory, attention abilities, and executive function. DATA CONCLUSION: Glymphatic function may be impaired in mTBI reflected by DTI-ALPS. Glymphatic dysfunction may cause cognitive impairment related to global white matter damage after mTBI. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Cardiomyocyte-specific Peli1 contributes to the pressure overload-induced cardiac fibrosis through miR-494-3p-dependent exosomal communication.

Cardiac fibrosis is an essential pathological process in pressure overload (PO)-induced heart failure. Recently, myocyte-fibroblast communication is proven to be critical in heart failure, in which, pathological growth of cardiomyocytes (CMs) may promote fibrosis via miRNAs-containing exosomes (Exos). Peli1 regulates the activation of NF-κB and AP-1, which has been demonstrated to engage in miRNA transcription in cardiomyocytes. Therefore, we hypothesized that Peli1 in CMs regulates the activation of cardiac fibroblasts (CFs) through an exosomal miRNA-mediated paracrine mechanism, thereby promoting cardiac fibrosis. We found that CM-conditional deletion of Peli1 improved PO-induced cardiac fibrosis. Moreover, Exos from mechanical stretch (MS)-induced WT CMs (WT MS-Exos) promote activation of CFs, Peli1-/- MS-Exos reversed it. Furthermore, miRNA microarray and qPCR analysis showed that miR-494-3p was increased in WT MS-Exos while being down regulated in Peli1-/- MS-Exos. Mechanistically, Peli1 promoted miR-494-3p expression via NF-κB/AP-1 in CMs, and then miR-494-3p induced CFs activation by inhibiting PTEN and amplifying the phosphorylation of AKT, SMAD2/3, and ERK. Collectively, our study suggests that CMs Peli1 contributes to myocardial fibrosis via CMs-derived miR-494-3p-enriched exosomes under PO, and provides a potential exosomal miRNA-based therapy for cardiac fibrosis.

Impact of age on the postural stability measured by a virtual reality tracker-based posturography and a pressure platform system.

BACKGROUND: Center of pressure (CoP) parameters are commonly used to evaluate age-related changes in postural control during standing. However, they mainly reflect ankle strategies and provide limited information about hip strategies, which are essential for postural control among the aged population. Body displacement at the lumbar level (LD) can be used as a proxy for hip strategies. OBJECTIVES: We set up a virtual reality tracker-based posturography to measure LD and compared the CoP and LD parameters in two age groups to explore the roles of ankle and hip strategies during bipedal stance. METHODS: Twenty-seven older healthy participants (63.8 ± 7.1 years old) and 27 younger controls (31.7 ± 9.9 years old) performed four standing tasks with their postural steadiness measured simultaneously with both systems under four stance conditions (combination of eyes-open/eyes-closed and wide-based/narrow-based). Five parameters were calculated from the trajectories of the CoP and LD. The difference in the parameters between two groups was analyzed with the Mann-Whitney U test. The discriminative ability of the parameters from the two systems was computed by the receiver operating characteristic curve analysis and area under the curve (AUC). We also used the intraclass correlation coefficient (ICC) to assess the correlation between two measures. RESULTS: Most of the parameters obtained from both systems were significantly different between the younger and older groups. Mean velocity in the medial-lateral and anterior-posterior directions could effectively discriminate age-related changes, especially with the LD parameters. The receiver's operation curve analysis gained the largest AUC (0.85 with both systems) with mean velocity in the medial-lateral direction during narrow-based standing with eyes closed. Meanwhile, we observed a low correlation between parameters obtained from the two methods in velocity measures, with the lowest ICC in the mean velocity in the medial-lateral direction in the older group (ICC = 0.34 ~ 0.41). CONCLUSION: Both systems could differentiate age-related changes in postural steadiness, but with dissociated information about mean velocity, especially the mean velocity in the medial-lateral direction in the older group. The results support the complimentary role of using tracker-based posturography to understand the effect of age on the mechanisms of postural control.

Application of a virtual reality tracker-based system to measure seated postural stability in stroke patients.

BACKGROUND: Postural stability while sitting is an important indicator of balance and an early predictor for future functional improvement in neurorehabilitation, but the evaluation is usually dependent on clinical balance function measures. Meanwhile, instrumental posturography has been used widely to obtain quantitative data and characterize balance abilities and underlying control mechanisms, but not as often for sitting balance. Moreover, traditional kinetic methods using a force platform to test sitting stability often require modification and are costly. We proposed a tracker-based posturography with a commercial virtual reality system, the VIVE Pro system (HTC, Inc. Taiwan), to record the trunk displacement (TD) path with a lumbar tracker for evaluation of sitting stability. The goals were to test the reliability and validity of the TD parameters among stroke patients. METHODS: Twenty-one stroke individuals and 21 healthy adults had their postural sway measured with this system under four sitting conditions, i.e., sitting on a solid surface or a soft surface, with eyes open or closed. The test-retest reliability of the TD parameters was evaluated with intraclass correlation coefficients in 22 participants. We also tested the discriminative validity of these parameters to discriminate between stroke and healthy controls, and among four sitting conditions. Furthermore, the TD parameters were correlated with the three balance function tests: the Berg Balance Scale (BBS), the Postural Assessment Scale for Stroke Patients (PASS) and the Function in Sitting Test (FIST). RESULTS: The results indicated that the TD parameters obtained by tracker-based posturography had mostly moderate to good reliability across the four conditions, with a few exceptions in the solid surface and eyes open tasks. The TD parameters could discriminate the postural stability between sitting on solid and soft surfaces. The stroke group had more seated postural sway than the control group, especially while sitting on a soft surface. In addition, velocity measures in the sagittal and frontal planes had moderate to high correlations with the PASS and BBS scores. CONCLUSIONS: This tracker-based system is a cost-effective option for the clinical assessment of body stability for stroke patients in a seated position and shows acceptable reliability and validity.

Asprosin in the Paraventricular Nucleus Induces Sympathetic Activation and Pressor Responses via cAMP-Dependent ROS Production.

Asprosin is a newly discovered adipokine that is involved in regulating metabolism. Sympathetic overactivity contributes to the pathogenesis of several cardiovascular diseases. The paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the regulation of sympathetic outflow and blood pressure. This study was designed to determine the roles and underlying mechanisms of asprosin in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male adult SD rats under anesthesia. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) were recorded, and PVN microinjections were performed bilaterally. Asprosin mRNA and protein expressions were high in the PVN. The high asprosin expression in the PVN was involved in both the parvocellular and magnocellular regions according to immunohistochemical analysis. Microinjection of asprosin into the PVN produced dose-related increases in RSNA, MAP, and HR, which were abolished by superoxide scavenger tempol, antioxidant N-acetylcysteine (NAC), and NADPH oxidase inhibitor apocynin. The asprosin promoted superoxide production and increased NADPH oxidase activity in the PVN. Furthermore, it increased the cAMP level, adenylyl cyclase (AC) activity, and protein kinase A (PKA) activity in the PVN. The roles of asprosin in increasing RSNA, MAP, and HR were prevented by pretreatment with AC inhibitor SQ22536 or PKA inhibitor H89 in the PVN. Microinjection of cAMP analog db-cAMP into the PVN played similar roles with asprosin in increasing the RSNA, MAP, and HR, but failed to further augment the effects of asprosin. Pretreatment with PVN microinjection of SQ22536 or H89 abolished the roles of asprosin in increasing superoxide production and NADPH oxidase activity in the PVN. These results indicated that asprosin in the PVN increased the sympathetic outflow, blood pressure, and heart rate via cAMP-PKA signaling-mediated NADPH oxidase activation and the subsequent superoxide production.

Inhibition of miR-135a-5p attenuates vascular smooth muscle cell proliferation and vascular remodeling in hypertensive rats.

Proliferation of vascular smooth muscle cells (VSMCs) greatly contributes to vascular remodeling in hypertension. This study is to determine the roles and mechanisms of miR-135a-5p intervention in attenuating VSMC proliferation and vascular remodeling in spontaneously hypertensive rats (SHRs). MiR-135a-5p level was raised, while fibronectin type III domain-containing 5 (FNDC5) mRNA and protein expressions were reduced in VSMCs of SHRs compared with those of Wistar-Kyoto rats (WKYs). Enhanced VSMC proliferation in SHRs was inhibited by miR-135a-5p knockdown or miR-135a-5p inhibitor, but exacerbated by miR-135a-5p mimic. VSMCs of SHRs showed reduced myofilaments, increased or even damaged mitochondria, increased and dilated endoplasmic reticulum, which were attenuated by miR-135a-5p inhibitor. Dual-luciferase reporter assay shows that FNDC5 was a target gene of miR-135a-5p. Knockdown or inhibition of miR-135a-5p prevented the FNDC5 downregulation in VSMCs of SHRs, while miR-135a-5p mimic inhibited FNDC5 expressions in VSMCs of both WKYs and SHRs. FNDC5 knockdown had no significant effects on VSMC proliferation of WKYs, but aggravated VSMC proliferation of SHRs. Exogenous FNDC5 or FNDC5 overexpression attenuated VSMC proliferation of SHRs, and prevented miR-135a-5p mimic-induced enhancement of VSMC proliferation of SHR. MiR-135a-5p knockdown in SHRs attenuated hypertension, normalized FNDC5 expressions and inhibited vascular smooth muscle proliferation, and alleviated vascular remodeling. These results indicate that miR-135a-5p promotes while FNDC5 inhibits VSMC proliferation in SHRs. Silencing of miR-135a-5p attenuates VSMC proliferation and vascular remodeling in SHRs via disinhibition of FNDC5 transcription. Either inhibition of miR-135a-5p or upregulation of FNDC5 may be a therapeutically strategy in attenuating vascular remodeling and hypertension.

Clinical characteristics of concurrent primary aldosteronism and renal artery stenosis: A retrospective case-control study.

Background: Rare cases of concurrent primary aldosteronism (PA) and renal artery stenosis (RAS) have been reported. Methods: In this retrospective case-control study, we selected a cohort of 10 PA with RAS patients and a control group of 20 PA without RAS patients from January 1, 2006, to January 1, 2016.  Results: All patients presented with refractory hypertension, and a nonstatistically significant trend toward lower mean serum potassium was seen in the PA with RAS group (p =.07). PA with RAS patients had lower mean orthostatic aldosterone-to-renin ratios (38.4 ± 41.4 ng dL-1/ng mL-1 h-1 vs. 87.4.4 ± 38.4 ng dL-1/ng mL-1 h-1, respectively; p < .01) and a higher false-negative rate (50% vs. 15%, respectively; p < .05) compared with controls. All misdiagnosed patients had the diagnosis of PA confirmed when we revaluated the repeated screening and confirmative tests because of residual hypertension or hypokalemia after successful revascularization of renal artery stenosis.  Conclusions: PA is easily missed in patients with RAS because of the high false-negative rate for screening tests. RAS patients with residual hypertension after successful renal angioplasty should be monitored for coexisting PA. Reevaluation of screening and confirmatory tests is helpful in establishing the correct diagnoses.

Experimental Imaging Study of Encephalomalacia Fluid-Attenuated Inversion Recovery (FLAIR) Hyperintense Lesions in Posttraumatic Epilepsy.

This study introduced new MRI techniques such as neurite orientation dispersion and density imaging (NODDI); NODDI applies a three-compartment tissue model to multishell DWI data that allows the examination of both the intra- and extracellular properties of white matter tissue. This, in turn, enables us to distinguish the two key aspects of axonal pathology-the packing density of axons in the white matter and the spatial organization of axons (orientation dispersion (OD)). NODDI is used to detect possible abnormalities of posttraumatic encephalomalacia fluid-attenuated inversion recovery (FLAIR) hyperintense lesions in neurite density and dispersion. Methods. 26 epilepsy patients associated with FLAIR hyperintensity around the trauma encephalomalacia region were in the epilepsy group. 18 posttraumatic patients with a FLAIR hyperintense encephalomalacia region were in the nonepilepsy group. Neurite density and dispersion affection in FLAIR hyperintense lesions around encephalomalacia were measured by NODDI using intracellular volume fraction (ICVF), and we compare these findings with conventional diffusion MRI parameters, namely, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Differences were compared between the epilepsy and nonepilepsy groups, as well as in the FLAIR hyperintense part and in the FLAIR hypointense part to try to find neurite density and dispersion differences in these parts. Results. ICVF of FLAIR hyperintense lesions in the epilepsy group was significantly higher than that in the nonepilepsy group (P < 0.001). ICVF reveals more information of FLAIR(+) and FLAIR(-) parts of encephalomalacia than OD and FA and ADC. Conclusion. The FLAIR hyperintense part around encephalomalacia in the epilepsy group showed higher ICVF, indicating that this part may have more neurite density and dispersion and may be contributing to epilepsy. NODDI indicated high neurite density with the intensity of myelin in the FLAIR hyperintense lesion. Therefore, NODDI likely shows that neurite density may be a more sensitive marker of pathology than FA.

Cooperative Syngas Production and C-N Bond Formation in One Photoredox Cycle.

Solar-driven syngas production by CO2 reduction provides a sustainable strategy to produce renewable feedstocks. However, this promising reaction often suffers from tough CO2 activation, sluggish oxidative half-reaction kinetics and undesired by-products. Herein, we report a function-oriented strategy of deliberately constructing black phosphorus quantum dots-ZnIn2 S4 (BP/ZIS) heterostructures for solar-driven CO2 reduction to syngas, paired with selectively oxidative C-N bond formation, in one redox cycle. The optimal BP/ZIS heterostructure features the enhanced charge-carrier separation and enriched active sites for cooperatively photocatalytic syngas production with a tunable ratio of CO/H2 and efficient oxidation of amines to imines with high conversion and selectivity. This prominent catalytic performance arises from the efficient electronic coupling between black phosphorus quantum dots and ZnIn2 S4 , as well as the optimized adsorption strength for key reaction intermediates, as supported by both experimental and theoretical investigations. We also demonstrate a synergistic interplay between CO2 reduction and amine dehydrogenation oxidation, rather than simply collecting these two single half-reactions in this dual-functional photoredox system.

Interleukin-1ß in hypothalamic paraventricular nucleus mediates excitatory renal reflex.

Chemical stimulation of kidney causes sympathetic activation and pressor responses in rats. The excitatory renal reflex (ERR) is mediated by angiotensin type 1 receptor (AT1R) and superoxide anions in hypothalamic paraventricular nucleus (PVN). The aim of this study is to determine whether interleukin-1ß (IL-1ß) in the PVN mediates the ERR, and whether the IL-1ß production in the PVN is dependent on the AT1R-superoxide anion signaling. Experiments were performed in adult rats under anesthesia. The ERR was induced by renal infusion of capsaicin, and evaluated by the responses of the contralateral renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP). Inhibition of IL-1ß production with MCC950 in the PVN dose-dependently inhibited the capsaicin-induced ERR and sympathetic activation. The PVN microinjection of IL-1 receptor antagonist IL-1Ra or specific IL-1ß antibody abolished the capsaicin-induced ERR, while IL-1ß enhanced the ERR. Renal infusion of capsaicin promoted p65-NFκB phosphorylation and IL-1ß production in the PVN, which were prevented by PVN microinjection of NADPH oxidase inhibitor apocynin or the superoxide anion scavenger tempol. The PVN microinjection of NFκB inhibitor BMS-345541 abolished the capsaicin induced-ERR and IL-1ß production, but not the NADPH oxidase activation and superoxide anion production. Furthermore, capsaicin-induced p65-NFκB phosphorylation and IL-1ß production in the PVN were prevented by AT1R antagonist losartan, or angiotensin converting enzyme inhibitor captopril. These results indicate that capsaicin-induced ERR and sympathetic activation are mediated by IL-1ß in the PVN. The IL-1ß production in the PVN is dependent on the AT1R-mediated superoxide anion generation and NFκB activation.

Unexpected Boosted Solar Water Oxidation by Nonconjugated Polymer-Mediated Tandem Charge Transfer.

Conjugated polymers are deemed as conductive carrier mediators for engendering the π electrons along the molecular framework, while the role of nonconjugated insulated polymers has been generally overlooked without the capability to participate in the solar-powered oxidation-reduction kinetics and charge-transfer process. Alternatively, considering the ultrashort charge lifetime and significant deficiency of metal nanocluster (NC)-based photosystems, the fine tuning of charge migration over atomically precise ultrasmall metal NCs as novel light-harvesting antennas has so far not yet been unleashed. Here, we unlock the charge-transfer capability of a nonconjugated polymer to modulate the charge flow over metal NCs (Aux and Au25) by such a solid-state nonconductive polymer via a conceptually new chemistry strategy by which l-glutathione (GSH)-capped gold (Aux@GSH) NCs and poly(diallyl-dimethylammonium chloride) (PDDA) were alternately self-assembled on the metal oxide (MO: WO3, Fe2O3, and TiO2) substrates. The ultrathin nonconjugated PDDA interim layer periodically intercalated in-between Aux (Au25) NC layers concurrently serves as an unexpected charge-transfer mediator to foster the unidirectional electron flow from Aux(Au25) NCs to MOs by forming a tandem charge-transfer chain, hence endowing the multilayered MO/(PDDA-Aux)n heterostructures with significantly boosted photoelectrochemical water oxidation performance under light irradiation. The unanticipated role of PDDA as a cascade charge mediator is demonstrated to be universal. Our work would unlock the potential charge-transport capability of nonconjugated polymers as a novel charge mediator for solar-to-chemical conversion.

Coexistence of the BRCA1 and KRAS mutations in a patient with salivary gland carcinoma arising in mediastinal mature teratoma.

Teratoma with malignant transformation is a rare type of malignant teratoma. In the present case, we describe a patient with salivary gland carcinoma (SGC) generating in mediastinal mature teratoma. Next-generation sequencing showed BRCA1 and KRAS somatic mutations, which might be associated with malignant transformation of the mediastinal mature teratomas. To our knowledge, the present case is the first report of coexistence of BRCA1 and KRAS mutations in mature cystic teratoma with malignant transformation to SGC. And the tumor showed a good response to chemotherapy with cisplatin and paclitaxel according to the transformed histology.

Serum biomarkers combined with ultrasonography for early diagnosis of non-alcoholic fatty liver disease confirmed by magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) is notably accurate for even minimal degree of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). But routine use of MRS is limited by its cost and availability. In this study, we developed a diagnostic model combining ultrasonography with biomarkers to identify mild NAFLD, with MRS as the reference standard. A total of 422 eligible subjects were enrolled. The serum levels of fibroblast growth factor 21 (FGF21), cytokeratin 18 M65ED, proteinase 3, neutrophil elastase, alpha-1 antitrypsin, and neutrophil elastase/alpha-1 antitrypsin were measured using ELISA assays. We found that among the six biomarkers, only serum FGF21 was independently associated with intrahepatic triglyceride content (IHTC, standardized ß = 0.185, P < 0.001) and was an independent risk factor for mild NAFLD. Thus, we established a Mild NAFLD Model based on FGF21, alanine transaminase, triglycerides, and body mass index. The area under the receiver-operating characteristic curve of the Mild NAFLD Model was 0.853 (95% confidence interval: 0.816-0.886). Furthermore, a two-step approach combining ultrasonography with the Mild NAFLD Model displayed a better sensitivity for diagnosing mild NAFLD compared with each method alone, with a sensitivity of 97.32% and a negative predictive value of 85.48%. This two-step approach combining ultrasonography and the Mild NAFLD Model derived from serum FGF21 improves the diagnosis of mild NAFLD and can be applied to the early diagnosis of NAFLD in clinical practice.

Application of super-resolution track-density technique: Earlier detection of aging-related subtle alterations than morphological changes in corpus callosum from normal population?

BACKGROUND: There are rare quantitative fiber density measurement techniques based on voxel measure changes of each corpus callosum (CC) subsegment with age. PURPOSE: To observe the regularity of corpus callosum development in normal aging from subvoxel to macroscopic volume. STUDY TYPE: Retrospective. SUBJECTS: In all, 131 healthy volunteers divided into six age groups. FIELD STRENGTH/SEQUENCE: 3T MR with 32-channel head coil T1 -3D and diffusion-weighted imaging with six b-values in a 30 directions sequence. ASSESSMENT: Track-density imaging (TDI) was used to visualize the complexity and the differences occurring in corpus callosum (CC) with age. TDI were reconstructed with a higher spatial voxel resolution of 0.1 mm subvoxel; TDI values are recognized as a subvoxel metric of real tract density. We reconstructed track density maps by using probabilistic streamline tractography combined with constrained spherical deconvolution. The CC was segmented into five subregions, and TDI, volume, and fractional anisotropy (FA) of each subregion in all the groups were measured using T1 W-3D images and compared. STATISTICAL TEST: Polynomial regression was done to between age and (CC1, CC2, CC3, CC4, CC5) of TDI/volume/FA. Multiple comparisons test two-way analysis of variance (ANOVA) were used to compare the differences between different age groups and sex groups in each subregion. Fisher's least significant difference test was used for the correction of the multiple comparisons. RESULTS: From the 20-70 age groups, TDI values of CC2, CC3, and CC4 increased until 40 years, when they were highest, and then decreased. CC2 (7.35556, 7.56587, 8.06036, 7.53841, 6.6956, 6.56494), CC3 (7.75372, 8.41447, 9.13178, 8.72605, 7.50106, 5.69513), CC4 (8.63414, 9.1518, 9.22451, 9.03154, 8.11556, 7.1967). There was a significant difference in the CC3 TDI between the 50/60 years groups and the 60/70 years groups (P = 0.03853 and 0.00285, respectively). The volumes of CC2, CC3, and CC4 increased between 30 and 50 years and decreased between 50 and 60 years, CC2 (0.06557, 0.07244, 0.08062, 0.07353, 0.08576, 0.06294), CC3 (0.03421, 0.03867, 0.03891, 0.03916, 0.03058, 0.03658), CC4 (0.0242, 0.01948, 0.02445, 0.02887, 0.01938, 0.01956). FA of CC2, CC3, and CC4 decreased between years 40 and 60.CC2 (0.45981, 0.47392, 0.45654, 0.45702, 0.39982, 0.35767), CC3 (0.4628, 0.49056, 0.49701, 0.46667, 0.44795, 0.36799), CC4 (0.46599, 0.52887, 0.4971, 0.53257, 0.42861, 0.43158). DATA CONCLUSION: TDI had high sensitivity for the detection of age-related CC differences. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:164-175.

Prevalence of White Matter Hyperintensity in Young Clinical Patients.

OBJECTIVE. The purpose of this study was to investigate the prevalence of white matter hyperintensity (WMH) without specific causes in young clinical outpatients. MATERIALS AND METHODS. A total of 1249 young clinical outpatients who underwent an unenhanced head MRI examination between January 1, 2016, and December 31, 2016, were included in the study. The chi-square test was used to analyze differences in the prevalence and characteristics of WMH by sex, age, and history of cardiovascular disease (CVD). The prevalence of WMH among clinical patients with neurologic symptoms was also compared with that among participants without neurologic symptoms. Logistic regression was used to identify the patient characteristics that were the best predictors of WMH. RESULTS. The overall prevalence of WMH was 25.94% (324/1249). Most patients with WMH (85.49% [277/324]) had mild WMH, mainly in frontal and parietal subcortical white matter. There was no significant difference in the prevalence of WMH by sex (p > 0.05), but the prevalence of WMH was higher among older patients (p < 0.001) and patients with a history of CVD (p < 0.001). Compared with participants without neurologic symptoms, clinical patients with dizziness (p = 0.029) and light-headedness (p = 0.001) were more likely to have WMH, which was attributed to older age and CVD. Logistic regression analysis showed that age and CVD were the best predictors of WMH. CONCLUSION. WMH is frequently found in young clinical patients. Most WMH is the mild type and mainly located in frontal and parietal subcortical white matter. Older age and CVD are risk factors for WMH.

Cobalt(II)-Based 3D Coordination Polymer with Unusual 4,4,4-Connected Topology as a Dual-Responsive Fluorescent Chemosensor for Acetylacetone and Cr2O72.

A cobalt(II) coordination polymer with an unusual 4,4,4-connected network was hydrothermally synthesized and observed with high thermal, solvent, and pH stabilities. This polymer can serve as the first dual-responsive fluorescent chemosensor for the selective detection of acetylacetone and Cr2O72- ion (pH 3.0) in aqueous systems.

Effect of region of interest on ADC and interobserver variability in thyroid nodules.

BACKGROUND: To determine the effect of region of interest (ROI) on tumor's apparent diffusion coefficient (ADC) and interobserver variability in thyroid nodules. METHODS: Thirty-three individuals with 45 pathologically-confirmed thyroid nodules were assessed by preoperative diffusion-weighted imaging (DWI) with b values of 0 and 400 s/mm2, respectively. Two readers evaluated the ADC values of lesions based on three ROI techniques: whole-volume, single-slice and small solid-sample groups. Interobserver variability was analyzed for all ROI techniques, and the mean ADCs of benign and cancerous thyroid nodules were compared. RESULTS: For the mean ADCs of non-cancerous thyroid nodules, average differences and limits of agreement (LOAs) between readers were 0.00 [- 0.17-0.17] × 10- 3 mm2/s for whole-volume ROI (ICC = 0.967), 0.00 [- 0.26-0.26] × 10- 3 mm2/s for single-slice ROI (ICC = 0.932) and - 0.02 [- 0.38-0.41] × 10- 3 mm2/s for small solid-sample ROI (ICC = 0.823). For the mean ADCs of cancerous thyroid nodules, average differences and LOAs between readers were - 0.05 [- 0.23-0.13] × 10- 3 mm2/s (ICC = 0.885), 0.01 [- 0.23-0.25] × 10- 3 mm2/s (ICC = 0.839) and - 0.07 [- 0.52-0.39] × 10- 3 mm2/s (ICC = 0.579) for the three ROI methods, respectively. The mean ADC values were more scattered in the small solid-sample ROI group in comparison with the whole-volume and single-slice groups, in noncancerous and cancerous specimens. Of all three ROI techniques, whole-volume ROI-determined ADC had the highest combined sensitivity (80.0%), specificity (88.3%) and Youden index (0.683), with a cut-off of 1.84 × 10- 3 mm2/s. CONCLUSIONS: The ROI method overtly affects ADC measurements in benign and cancerous thyroid nodules. Small solid-sample ROI yielded the worst interobserver variability of average ADC measurements.

Fibronectin Type III Domain-Containing 5 Attenuates Liver Fibrosis Via Inhibition of Hepatic Stellate Cell Activation.

BACKGROUND/AIMS: Fibronectin type III domain-containing 5 (FNDC5) protein is involved in the beneficial effects of exercise on metabolism. FNDC5 attenuates hepatic steatosis induced by high fat diet (HFD). Here, we examined the effects of FNDC5 on liver fibrosis and underline mechanisms. METHODS: Experiments were carried out on wild-type and FNDC5-/- mice, primary mouse hepatic stellate cells (HSCs) and human hepatic stellate cell line (LX-2). The mice were fed with HFD for 6 months to induce liver fibrosis. Oxidized low density lipoprotein (oxLDL) were used to induce the activation of hepatic stellate cells and fibrosis in mouse HSCs and human LX-2 cells. H&E, Masson's trichrome staining and Sirius red staining were used for liver sections. Protein and mRNA expressions were evaluated with Western blot and RT-PCR, respectively. RESULTS: FNDC5 deficiency aggravated the HFD-induced liver fibrosis and HSCs activation in mice. It exacerbated the HFD-induced inhibition of AMPK phosphorylation, upregulation of connective tissue growth factor (CTGF) and transforming growth factor-ß (TGF-ß), and deposition of extracellular matrix (ECM) in liver of mice. Administration of FNDC5 attenuated oxLDL-induced AMPK deactivation, HSCs activation, CTGF and TGF-ß upregulation and ECM deposition in mouse HSCs. The beneficial effects of FNDC5 on oxLDL-induced AMPK dephosphorylation, HSCs activation and ECM deposition were prevented by the inhibition of AMPK with compound C in human LX-2 cells. However, the effects of FNDC5 on hepatic fibrosis in vivo in this study cannot be distinguished from its effects on adiposity and hepatic steatosis. CONCLUSIONS: FNDC5 deficiency aggravates HFD-induced liver fibrosis in mice. FNDC5 plays beneficial roles in attenuating liver fibrosis via AMPK phosphorylation-mediated inhibition of HSCs activation.