MFG-E8 Alleviates Cognitive Impairments Induced by Chronic Cerebral Hypoperfusion by Phagocytosing Myelin Debris and Promoting Remyelination.

Chronic cerebral hypoperfusion is one of the pathophysiological mechanisms contributing to cognitive decline by causing white matter injury. Microglia phagocytosing myelin debris in a timely manner can promote remyelination and contribute to the repair of white matter. However, milk fat globule-epidermal growth factor-factor 8 (MFG-E8), a microglial phagocytosis-related protein, has not been well studied in hypoperfusion-related cognitive dysfunction. We found that the expression of MFG-E8 was significantly decreased in the brain of mice after bilateral carotid artery stenosis (BCAS). MFG-E8 knockout mice demonstrated more severe BCAS-induced cognitive impairments in the behavioral tests. In addition, we discovered that the deletion of MFG-E8 aggravated white matter damage and the destruction of myelin microstructure through fluorescent staining and electron microscopy. Meanwhile, MFG-E8 overexpression by AAV improved white matter injury and increased the number of mature oligodendrocytes after BCAS. Moreover, in vitro and in vivo experiments showed that MFG-E8 could enhance the phagocytic function of microglia via the αVß3/αVß5/Rac1 pathway and IGF-1 production to promote the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes. Interestingly, we found that MFG-E8 was mainly derived from astrocytes, not microglia. Our findings suggest that MFG-E8 is a potential therapeutic target for cognitive impairments following cerebral hypoperfusion.

CD11c+ microglia promote white matter repair after ischemic stroke.

Ischemic stroke leads to white matter damage and neurological deficits. However, the characteristics of white matter injury and repair after stroke are unclear. Additionally, the precise molecular communications between microglia and white matter repair during the stroke rehabilitation phase remain elusive. In this current study, MRI DTI scan and immunofluorescence staining were performed to trace white matter and microglia in the mouse transient middle cerebral artery occlusion (tMCAO) stroke model. We found that the most serious white matter damage was on Day 7 after the ischemic stroke, then it recovered gradually from Day 7 to Day 30. Parallel to white matter recovery, we observed that microglia centered around the damaged myelin sheath and swallowed myelin debris in the ischemic areas. Then, microglia of the ischemic hemisphere were sorted by flow cytometry for RNA sequencing and subpopulation analysis. We found that CD11c+ microglia increased from Day 7 to Day 30, demonstrating high phagocytotic capabilities, myelin-supportive genes, and lipid metabolism associated genes. CD11c+ microglia population was partly depleted by the stereotactic injecting of rAAV2/6M-taCasp3 (rAAV2/6M-CMV-DIO-taCasp3-TEVp) into CD11c-cre mice. Selective depletion of CD11c+ microglia disrupted white matter repair, oligodendrocyte maturation, and functional recovery after stroke by Rotarod test, Adhesive Removal test, and Morris Water Maze test. These findings suggest that spontaneous white matter repair occurs after ischemic stroke, while CD11c+ microglia play critical roles in this white matter restorative progress.

Brain morphological alterations and their correlation to tumor differentiation and duration in patients with lung cancer after platinum chemotherapy.

Objective: Chemotherapy-related brain impairments and changes can occur in patients with lung cancer after platinum chemotherapy and have a substantial impact on survivors' quality of life. Therefore, it is necessary to understand the brain neuropathological alterations and response mechanisms to provide a theoretical basis for rehabilitation strategies. This study aimed to investigate the related brain morphological changes and clarified their correlation with clinical and pathological indicators in patients with lung cancer after platinum chemotherapy. Methods: Overall, 28 patients with chemotherapy, 56 patients without chemotherapy, and 41 healthy controls were categorized in three groups, matched for age, sex, and years of education, and included in the cross-sectional comparison of brain volume and cortical thickness. 14 matched patients before and after chemotherapy were subjected to paired comparison for longitudinal observation of brain morphological changes. Three-dimensional T1-weighted images were acquired from all participants, and quantitative parameters were calculated using the formula of the change from baseline. Correlation analysis was performed to evaluate the relationship between abnormal morphological indices and clinical information of patients. Results: Brain regions with volume differences among the three groups were mainly distributed in frontal lobe and limbic cortex. Additionally, significant differences in cerebrospinal fluid were observed in most ventricles, and the main brain regions with cortical thickness differences were the gyrus rectus and medial frontal cortex of the frontal lobe, transverse temporal gyrus of the temporal lobe, insular cortex, anterior insula, and posterior insula of the insular cortex. According to the paired comparison, decreased brain volumes in the patients after chemotherapy appeared in some regions of the frontal, parietal, temporal, and occipital lobes; limbic cortex; insular cortex; and lobules VI-X and decreased cortical thickness in the patients after chemotherapy was found in the frontal, temporal, limbic, and insular cortexes. In the correlation analysis, only the differentiation degree of the tumor and duration after chemotherapy were significantly correlated with imaging indices in the abnormal brain regions. Conclusions: Our findings illustrate the platinum-related brain reactivity morphological alterations which provide more insights into the neuropathological mechanisms of patients with lung cancer after platinum chemotherapy and empirical support for the details of brain injury related to cancer and chemotherapy.

Chemiexcited Photodynamic Therapy Integrated in Polymeric Nanoparticles Capable of MRI Against Atherosclerosis.

Background: Photodynamic therapy (PDT) has achieved continued success in the treatment of tumors, but its progress in the treatment of atherosclerosis has been limited, mainly due to the low tissue-penetration ability of the excitation light for photosensitizers. Methods: In this study, we designed a chemiexcited system producing singlet oxygen in an attempt to apply PDT for the treatment of atherosclerosis without the irradiation of external light. The system designed was polymeric nanoparticles (NPs) equipped with chemical fuel and photosensitizers, cross-linked with an Fe3+-catechol complex for stabilization and magnetic resonance imaging (MRI). Results: The system (FeCNPs for short) accumulated effectively in plaques, providing persistent and enhanced T 1-weighted contrast ability. FeCNPs also prevented progression of atherosclerosis via macrophage elimination, and obviously reduced plaque size and thickness revealed by T 1-weighted MRI. Expression of CD68, MCP1, and TNFα was significantly reduced after treatment. However, low doses of FeCNPs exhibited better therapeutic efficacy than high doses. Furthermore, low-dose FeCNPs exhibited effective macrophage elimination in aortic arches and abdominal aortae, but inefficiency in the thoracic aorta, aortic hiatus, and aorta-iliac bifurcation. Conclusion: This study provides the first example of a combination of MRI and chemiexcited PDT for atherosclerosis, evidencing the effectiveness of PDT and providing significant pointers for developing nanotherapy on atherosclerosis.

Pentoxifylline alleviates ischemic white matter injury through up-regulating Mertk-mediated myelin clearance.

BACKGROUND: Vascular dementia (VAD) is the second most common type of dementia lacking effective treatments. Pentoxifylline (PTX), a nonselective phosphodiesterase inhibitor, displays protective effects in multiple cerebral diseases. In this study, we aimed to investigate the therapeutic effects and potential mechanisms of PTX in VAD. METHODS: Bilateral common carotid artery stenosis (BCAS) mouse model was established to mimic VAD. Mouse behavior was tested by open field test, novel object recognition test, Y-maze and Morris water maze (MWM) tests. Histological staining, magnetic resonance imaging (MRI) and electron microscopy were used to define white matter integrity. The impact of PTX on microglia phagocytosis, peroxisome proliferator-activated receptors-γ (PPAR-γ) activation and Mer receptor tyrosine kinase (Mertk) expression was assessed by immunofluorescence, western blotting and flow cytometry with the application of microglia-specific Mertk knockout mice, Mertk inhibitor and PPAR-γ inhibitor. RESULTS: Here, we found that PTX treatment alleviated cognitive impairment in novel object recognition test, Y-maze and Morris water maze tests. Furthermore, PTX alleviated white matter injury in corpus callosum (CC) and internal capsule (IC) areas as shown by histological staining and MRI analysis. PTX-treatment group presented thicker myelin sheath than vehicle group by electron microscopy. Mechanistically, PTX facilitated microglial phagocytosis of myelin debris by up-regulating the expression of Mertk in BCAS model and primary cultured microglia. Importantly, microglia-specific Mertk knockout blocked the therapeutic effects of PTX in BCAS model. Moreover, Mertk expression was regulated by the nuclear translocation of PPAR-γ. Through modulating PPAR-γ, PTX enhanced Mertk expression. CONCLUSIONS: Collectively, our results demonstrated that PTX showed therapeutic potentials in VAD and alleviated ischemic white matter injury via modulating Mertk-mediated myelin clearance in microglia.

Effects of cognitive reserve proxies on cognitive function and frontoparietal control network in subjects with white matter hyperintensities: A cross-sectional functional magnetic resonance imaging study.

AIMS: This study aimed to analyze the potential association between cognition reserve (CR) components, including education, working activity, and leisure time activity, and cognitive function in subjects with white matter hyperintensities (WMH). The study also explored the role of the frontoparietal control network (FPCN) in such association. METHODS: White matter hyperintensities subjects with and without cognitive impairment (CI) were evaluated with multimodal magnetic resonance imaging, neuropsychological testing, and CR survey. FPCN patterns were assessed with dorsolateral prefrontal cortex seed-based functional connectivity analysis. RESULTS: Education was positively associated with cognitive function in WMH subjects with or without CI, whereas working activity and leisure time activity were positively associated with cognitive function only in those without CI. Similarly, education was associated with bilateral FPCN in both WMH groups, whereas working activity and leisure time activity were associated with bilateral FPCN mainly in the group without CI. Furthermore, FPCN partially mediated the association between education and cognitive function in both WMH groups. CONCLUSION: Education showed a positive impact on cognitive function in WMH subjects regardless of their cognitive status, whereas working activity and leisure time activity exhibited beneficial effects only in those without CI. The FPCN mediated the beneficial effect of education on cognitive function.

The flexibility of cognitive reserve in regulating the frontoparietal control network and cognitive function in subjects with white matter hyperintensities.

High cognitive reserve (CR) protects against cognitive decline in individuals with white matter hyperintensities (WMH). However, the functional mechanisms remain relatively unknown. This work aimed to explore the effects of CR on the frontoparietal control network (FPCN) and cognitive function in subjects with WMH. One hundred and thirty-seven subjects with WMH and 95 control subjects without WMH underwent neuropsychological testing, CR assessments, and multimodal magnetic resonance imaging (MRI) scanning. A mixed analysis of covariance with CR level (high CR vs. low CR) and WMH status (with WMH vs. without WMH) as fixed factors was performed on the FPCN. WMH volume was negatively correlated with global cognitive function in subjects with low CR not in those with high CR, suggesting a buffering effect of high CR. An interaction between CR and WMH was detected on the right FPCN in frontal regions. Specifically, control subjects with high CR had significantly higher functional connectivity (FC) in frontal regions than control subjects with low CR, whereas this relation was inverted in WMH subjects. Correlative analyses showed positive associations of the FC with cognitive performance in both WMH subjects and control subjects, although the associations were not significant after correction for multiple comparisons. In conclusion, CR differentially regulated the FPCN in frontal regions between subjects with WMH and those without WMH. This regulation supports the flexibility of CR in regulating brain function and may underlie the effects of CR on cognitive function in WMH subjects.

The efficacy of gray matter atrophy and cognitive assessment in differentiation of aMCI and naMCI.

BACKGROUND: Mild cognitive impairment (MCI) is a heterogeneous entity that can be categorized into related but different subtypes. In this study, we analyzed the gray matter structural changes of amnestic MCI (aMCI) and non-amnestic MCI (naMCI), and how it resulted in diverse cognitive impairment. METHODS: Altogether 77 individuals were recruited, including 28 cognitively normal controls (NC), 25 naMCI subjects, and 24 aMCI subjects. All participants underwent a 3.0 T magnetic resonance (MR) scan and a detailed neuropsychological examination. Cortical thickness and subcortical nuclei volume were extracted by Freesurfer software and compared among groups. The areas with significant differences were further analyzed by general linear regression to identify the risk factors of each cognitive impairment subtypes. RESULTS: Significant differences were observed in bilateral hippocampi, amygdala, thalamus, accumbens, left transverse temporal gyrus and left precuneus among groups. AMCI and naMCI were significantly different in the right hippocampus, bilateral amygdala, left precuneus, and left transverse temporal gyrus. Linear regression analysis revealed that the atrophy of left precuneus was a risk factor of memory, executive function (EF) and visuospatial impairment (p < 0.001). The atrophy of left amygdala, right accumbens and left thalamus were risk factors of memory, EF and language impairment respectively (p < 0.05). CONCLUSIONS: These findings confirmed that different gray matter structural changes could lead to specific neuropsychological features in MCI subtypes. Thorough understanding of MCI subtypes and the underlying pathology would be beneficial for precise diagnosis and intervention.

Lateralized Contributions of Medial Prefrontal Cortex Network to Episodic Memory Deficits in Subjects With Amnestic Mild Cognitive Impairment.

Both episodic memory and executive function are impaired in amnestic mild cognitive impairment (aMCI) subjects, but it is unclear if these impairments are independent or interactive. The present study aimed to explore the relationship between episodic memory deficits and executive function deficits, and the underlying functional mechanisms in aMCI subjects. Thirty-one aMCI subjects and 27 healthy subjects underwent neuropsychological tests and multimodal magnetic resonance imaging (MRI) scans. Hippocampal networks and medial prefrontal cortex (MPFC) networks were identified based on resting-sate functional MRI (fMRI) data. AMCI subjects displayed lower episodic memory scores and executive function scores than control subjects, and the episodic memory scores were positively correlated with the executive function scores in aMCI subjects. Brain network analyses showed an interaction between the hippocampal networks and the MPFC networks, and the interaction was significantly associated with the episodic memory scores and the executive function scores. Notably, aMCI subjects displayed higher functional connectivity (FC) of the right hippocampal network with the right prefrontal cortex than did control subjects, but this difference disappeared when controlling for the MPFC networks. Furthermore, the effects of the MPFC networks on the hippocampal networks were significantly associated with the episodic memory scores in aMCI subjects. The present findings suggested that the episodic memory deficits in aMCI subjects could be partially underpinned by the modulation of the MPFC networks on the hippocampal networks.

Ultrasmall Fe(III)-Tannic Acid Nanoparticles To Prevent Progression of Atherosclerotic Plaques.

Macrophage accumulation is central to the pathogenesis of atherosclerotic plaques. Reducing macrophages in plaques is an appealing approach to attenuate the development of atherosclerosis. Chemodynamic therapy, specifically inhibiting hydrogen peroxide (H2O2)-rich cells in slightly acidic microenvironment, has emerged as a new method in tumor treatment. Herein, we manufactured ultrasmall dopamine-modified hyaluronic acid (HD)-stabilized Fe(III)-tannic acid nanoparticles (HFTNPs). HFTNPs can specifically accumulate in inflammatory macrophages in atherosclerotic plaques, provide brighter magnetic resonance images, promote reactive oxygen species (ROS) generation, and induce the death of inflammatory macrophages without damaging normal cells and tissues. In conclusion, HFTNPs have a tremendous potential as safe and effective diagnostic and therapeutic reagents for atherosclerosis.

Postmortem 9.4-T MRI for Fetuses With Congenital Heart Defects Diagnosed in the First Trimester.

OBJECTIVE: To evaluate the feasibility of 9. 4-T postmortem MRI (pm-MRI) for assessment of major congenital heart defects (CHD) cases terminated in the early stage of gestation. METHODS: Fetuses with CHD detected by the detailed first-trimester ultrasound scan and terminated before 18 gestational weeks were recruited between January 2018 and June 2020. All fetuses were offered 9.4-T pm-MRI examinations and those terminated over 13+6 weeks were offered conventional autopsies simultaneously. Findings of pm-MRI were compared with those of conventional autopsy and prenatal ultrasound. RESULTS: A total of 19 fetuses with major CHD were analyzed, including 6 cases of the atrioventricular septal defect, 5 cases of Tetralogy of Fallot, 3 cases of hypoplastic left heart syndrome, 1 case of tricuspid atresia, 1 case of transposition of the great arteries, 1 case of severe tricuspid regurgitation, and 2 cases of complex CHD. Pm-MRI had concordant findings in 73.7% (14/19) cases, discordant findings in 15.8% (3/19) cases, and additional findings in 10.5% (2/19) cases when compared with prenatal ultrasound. Pm-MRI findings were concordant with autopsy in all 8 CHD cases terminated over 13+6 weeks. CONCLUSION: It is feasible to exhibit the structure of fetal heart terminated in the first trimester clearly on 9.4-T pm-MRI with an optimized scanning protocol. High-field pm-MRI could provide medical imaging information of CHD for those terminated in the early stage of gestation, especially for those limited by conventional autopsy.

Long Longitudinal Tract Lesion Contributes to the Progression of Alzheimer's Disease.

Background: The degenerative pattern of white matter (WM) microstructures during Alzheimer's disease (AD) and its relationship with cognitive function have not yet been clarified. The present research aimed to explore the alterations of the WM microstructure and its impact on amnestic mild cognitive (aMCI) and AD patients. Mechanical learning methods were used to explore the validity of WM microstructure lesions on the classification in AD spectrum disease. Methods: Neuropsychological data and diffusion tensor imaging (DTI) images were collected from 28 AD subjects, 31 aMCI subjects, and 27 normal controls (NC). Tract-based spatial statistics (TBSS) were used to extract diffusion parameters in WM tracts. We performed ANOVA analysis to compare diffusion parameters and clinical features among the three groups. Partial correlation analysis was used to explore the relationship between diffusion metrics and cognitive functions controlling for age, gender, and years of education. Additionally, we performed the support vector machine (SVM) classification to determine the discriminative ability of DTI metrics in the differentiation of aMCI and AD patients from controls. Results: As compared to controls or aMCI patients, AD patients displayed widespread WM lesions, including in the inferior longitudinal fasciculus, inferior fronto-occipital fasciculi, and superior longitudinal fasciculus. Significant correlations between fractional anisotropy (FA), mean diffusivity (MD), and radial diffusion (RD) of the long longitudinal tract and memory deficits were found in aMCI and AD groups, respectively. Furthermore, through SVM classification, we found DTI indicators generated by FA and MD parameters can effectively distinguish AD patients from the control group with accuracy rates of up to 89 and 85%, respectively. Conclusion: The WM microstructure is extensively disrupted in AD patients, and the WM integrity of the long longitudinal tract is closely related to memory, which would hold potential value for monitoring the progression of AD. The method of classification based on SVM and WM damage features may be objectively helpful to the classification of AD diseases.

Aberrant White Matter Microstructure as a Potential Diagnostic Marker in Alzheimer's Disease by Automated Fiber Quantification.

Neuroimaging evidence has suggested white matter microstructure are heavily affected in Alzheimer's disease (AD). However, whether white matter dysfunction is localized at the specific regions of fiber tracts and whether they would be a potential biomarker for AD remain unclear. By automated fiber quantification (AFQ), we applied diffusion tensor images from 25 healthy controls (HC), 24 amnestic mild cognitive impairment (aMCI) patients and 18 AD patients to create tract profiles along 16 major white matter fibers. We compared diffusion metrics [Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR)] between groups. To assess the diagnostic value, we applied a random forest (RF) classifier, a type of machine learning method. In the global tract level, we found that aMCI and AD patients showed higher MD, DA, and DR values in some fiber tracts mostly in the left hemisphere compared to HC. In the point-wise level, widespread disruption were distributed on specific locations of different tracts. The point-wise MD measurements presented the best classification performance with respect to differentiating AD from HC. The two most important variables were localized in the prefrontal potion of left uncinate fasciculus and anterior thalamic radiation. In addition, the point-wise DA in the posterior component of the left cingulum cingulate displayed the most robust discriminative ability to identify AD from aMCI. Our findings provide evidence that white matter abnormalities based on the AFQ method could be as a diagnostic biomarker in AD.

AC/DC hybrid electric field measurement method based on Pockels effect and electric field modulation.

The electromagnetic environment under transmission lines is a concern for high-voltage transmission. For transmission corridors in which alternating-current (AC) and direct-current (DC) transmission lines are on the same tower, the electromagnetic environment at ground level is complex because of the AC/DC hybrid electric field. Generally, different instruments are used for measuring AC and DC electric fields, making it difficult to measure such fields simultaneously. Thus, we propose a method for AC/DC hybrid electric field measurement based on the Pockels effect and electric field modulation. The principle of the measurement is discussed in detail. An experimental platform is set up to verify the feasibility and effectiveness of the proposed method and to calibrate the sensor. It shows that the sensor realizes simultaneous measurement of AC and DC electric field intensities as well as judgment of the polarity of the DC electric field. The measurable range is 1.05-150 kV/m (peak-to-peak value) for the AC electric field and 1.23-150 kV/m for the DC electric field with a maximum measurement error of less than 5%. The sensor has good repeatability, linearity, and low hysteresis, which can be used in power grids for AC/DC hybrid electric field measurements.

Altered sulcogyral patterns of orbitofrontal cortex in patients with mild cognitive impairment.

Mild cognitive impairment (MCI) is increasingly recognized as a risk factor for Alzheimer's disease (AD). Neuroimaging studies have revealed structural abnormalities in the orbitofrontal cortex (OFC) in MCI patients, while other findings fail to report anatomical alterations. Accordingly, structural changes in this brain region amongst MCI patients has not been well characterized. Given that OFC sulcogyral organization has increasingly been demonstrated as a reliable pre-morbid marker of pathological conditions in several neuropsychiatric disorders, we examined the distribution of OFC sulcogyral patterns (classified into Type I, II and III) based on structural brain data from 68 MCI patients and 55 healthy controls. Our results, supported by both Frequentist and Bayesian statistics, showed that MCI patients exhibited an increased prevalence of Type II pattern compared with healthy controls, particularly in the right hemisphere. Meanwhile, MCI patients showed a decreased prevalence of Type I pattern compared with healthy controls. Taken together, our results reveal a skewed distribution of OFC sulcogyral in MCI patients, possibly reflecting a potential neurodevelopmental risk marker of MCI.

Current sensor based on an integrated micro-ring resonator and superparamagnetic nanoparticles.

An ultra-small integrated photonic current sensor based on a silicon micro-ring resonator (MRR) with a cladding layer of Fe3O4 superparamagnetic nanoparticles (SPNPs) is demonstrated. In the magnetic field generated by an alternating current, the Fe3O4 SPNPs lose energy and change the MRR temperature, which leads to a spectral shift in the MRR transmission. The sensor was demonstrated with good linearity in the frequency range 0-60 kHz and current amplitudes from 0 to 0.5 A. This work provides a basis for integrated micro-current sensors, and promotes the development of photoelectric sensors on silicon substrates.

Deep Learning-Based Classification and Voxel-Based Visualization of Frontotemporal Dementia and Alzheimer's Disease.

Frontotemporal dementia (FTD) and Alzheimer's disease (AD) have overlapping symptoms, and accurate differential diagnosis is important for targeted intervention and treatment. Previous studies suggest that the deep learning (DL) techniques have the potential to solve the differential diagnosis problem of FTD, AD and normal controls (NCs), but its performance is still unclear. In addition, existing DL-assisted diagnostic studies still rely on hypothesis-based expert-level preprocessing. On the one hand, it imposes high requirements on clinicians and data themselves; On the other hand, it hinders the backtracking of classification results to the original image data, resulting in the classification results cannot be interpreted intuitively. In the current study, a large cohort of 3D T1-weighted structural magnetic resonance imaging (MRI) volumes (n = 4,099) was collected from two publicly available databases, i.e., the ADNI and the NIFD. We trained a DL-based network directly based on raw T1 images to classify FTD, AD and corresponding NCs. And we evaluated the convergence speed, differential diagnosis ability, robustness and generalizability under nine scenarios. The proposed network yielded an accuracy of 91.83% based on the most common T1-weighted sequence [magnetization-prepared rapid acquisition with gradient echo (MPRAGE)]. The knowledge learned by the DL network through multiple classification tasks can also be used to solve subproblems, and the knowledge is generalizable and not limited to a specified dataset. Furthermore, we applied a gradient visualization algorithm based on guided backpropagation to calculate the contribution graph, which tells us intuitively why the DL-based networks make each decision. The regions making valuable contributions to FTD were more widespread in the right frontal white matter regions, while the left temporal, bilateral inferior frontal and parahippocampal regions were contributors to the classification of AD. Our results demonstrated that DL-based networks have the ability to solve the enigma of differential diagnosis of diseases without any hypothesis-based preprocessing. Moreover, they may mine the potential patterns that may be different from human clinicians, which may provide new insight into the understanding of FTD and AD.

Enhanced Regional Homogeneity and Functional Connectivity in Subjects With White Matter Hyperintensities and Cognitive Impairment.

OBJECTIVE: White matter hyperintensities (WMH) is an important cause of vascular cognitive impairment (CI). However, a considerable portion of individuals with WMH do not develop CI. The present study aimed to investigate distinctive regional brain activity and connectivity patterns in WMH subjects with and without CI, who displayed comparable WMH burden. METHODS: Fourteen WMH subjects with CI, 16 WMH subjects without CI and 37 healthy subjects underwent multimodal MRI scans and neuropsychological tests. All WMH subjects displayed Fazekas grade 2 of WMH. Regional Homogeneity (ReHo) and functional connectivity (FC) patterns were identified based on resting-state functional MRI data. RESULTS: No significant differences in WMH volume, the number of WMH lesions and brain volume were shown between the 2 WMH groups. In contrast, the WMH with CI group showed higher ReHo in bilateral superior parietal gyrus (SPG)/superior occipital gyrus (SOG) than the WMH without CI group. Compared with the WMH without CI group, the WMH with CI group also displayed higher FC of the left SPG/SOG with frontal regions, and higher FC of the right SPG/SOG with parietal regions. Furthermore, higher FC of the left SPG/SOG with frontal regions were significantly associated with less worse executive dysfunction in WMH with CI subjects, suggesting a compensatory effect. CONCLUSION: Higher local coherence of activities in the SPG/SOG and higher connectivity of the SPG/SOG with parietal and frontal regions are related to CI in WMH subjects. The findings provide novel insights into functional alterations underlying the cognitive variety in WMH subjects.

[Correlation study on chemical constitutes of cardiac glycosides in Taxillus chinensis and its Nerium indicum host by UPLC-Q-TOF-MS/MS].

To build up an identification method on cardiac glycosides in Taxillus chinensis and its Nerium indicum host, and evaluate the influence on medicine quality from host to T. chinensis, ultra-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass-mass spectrometry(UPLC-Q-TOF-MS/MS)was applied. The samples of T. chinensis(harvested from N. indicum)and its N. indicum host were collected in field. The samples of T. chinensis(harvested from Morus alba)and its M. alba host was taken as control substance. All samples were extracted by ultrasonic extraction in 70% ethanol. Chromatographic separation was performed on an ACQUITY UPLC HSS T3 C_(18)(2.1 mm×100 mm,1.8 µm)column at 40 ℃. Gradient elution was applied, and the mobile phase was consisted of 0.1% formic acid water and acetonitrile. The 0.5 µL of sample solution was injected and the flow rate of the mobile phase was kept at 0.6 mL·min~(-1) in each run. It was done to identify cardiac glycosides and explore the chemical composition correlation in T. chinensis and its N. indicum host by analyzing positive and negative ion mode mass spectrometry data, elemental composition, cardiac glycoside reference substance and searching related literatures. A total of 29 cardiac glycosides were identified, 28 of it belonged to N. indicum host, 5 belonged to T. chinensis(harvested from N. indicum host), none of cardiac glycoside was identified in T. chinensis(harvested from M. alba host). The result could provide a reference in evaluating the influence in T. chinensis medicine quality from host. It was rapid, accurate, and comprehensive to identify cardiac glycosides in T. chinensis and its N. indicum host by UPLC-Q-TOF-MS/MS.

Identification and analysis of cardiac glycosides in Loranthaceae parasites Taxillus chinensis (DC.) Danser and Scurrula parasitica Linn. and their host Nerium indicum Mill.

To evaluate the effect of the host plant on the quality of Loranthaceae species as medicinal raw material, ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) was used to identify cardiac glycosides in Nerium indicum and its parasitic plant species Taxillus chinensis and Scurrula parasitica. Samples were collected from N. indicum and these parasites, while Morus alba and its parasite T. chinensis and Osmanthus fragrans and its parasite S. parasitica were used as controls. Based on mass spectrometry data and elemental composition analysis of positive and negative ion modes, in combination with standard cardiac glycosides and relevant literature, cardiac glycosides in N. indicum and its parasites T. chinensis and S. parasitica were identified, and their correlations were analyzed. A total of 29 cardiac glycosides were identified, among which 28 were found in N. indicum parasitized by T. chinensis; 25 cardiac glycosides were identified in the same host under attack by S. parasitica; five cardiac glycosides were identified in both T. chinensis and S. parasitica, which grew parasitically on N. indicum, whereas no cardiac glycosides were identified in M. alba parasitized by T. chinensis, or in O. fragrans parasitized by S. parasitica. We conclude that UPLC-Q-TOF-MS/MS technology can identify cardiac glycosides in N. indicum and parasites T. chinensis and S. parasitica rapidly, accurately, and thoroughly. N. indicum will transfer its own cardiac glycosides to its parasites through the special host-parasite interaction. Our results provide a reference basis for evaluating the influence of the host plant on the quality of medicinal compounds obtained from Loranthaceae species.