Alterations of voxel-wise spontaneous activity and corresponding brain functional networks in multiple system atrophy patients with mild cognitive impairment.

Emerging evidence has indicated that cognitive impairment is an underrecognized feature of multiple system atrophy (MSA). Mild cognitive impairment (MCI) is related to a high risk of dementia. However, the mechanism underlying MCI in MSA remains controversial. In this study, we conducted the amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) analyses to detect the characteristics of local neural activity and corresponding network alterations in MSA patients with MCI (MSA-MCI). We enrolled 80 probable MSA patients classified as cognitively normal (MSA-NC, n = 36) and MSA-MCI (n = 44) and 40 healthy controls. Compared with MSA-NC, MSA-MCI exhibited decreased ALFF in the right dorsal lateral prefrontal cortex (RDLPFC) and increased ALFF in the right cerebellar lobule IX and lobule IV-V. In the secondary FC analyses, decreased FC in the left inferior parietal lobe (IPL) was observed when we set the RDLPFC as the seed region. Decreased FC in the bilateral cuneus, left precuneus, and left IPL and increased FC in the right middle temporal gyrus were shown when we set the right cerebellar lobule IX as the seed region. Furthermore, FC of DLPFC-IPL and cerebello-cerebral circuit, as well as ALFF alterations, were significantly correlated with Montreal Cognitive Assessment scores in MSA patients. We also employed whole-brain voxel-based morphometry analysis, but no gray matter atrophy was detected between the patient subgroups. Our findings indicate that altered spontaneous activity in the DLPFC and the cerebellum and disrupted DLPFC-IPL, cerebello-cerebral networks are possible biomarkers of early cognitive decline in MSA patients.

Multimodal striatal neuromarkers in distinguishing parkinsonian variant of multiple system atrophy from idiopathic Parkinson's disease.

AIMS: To develop an automatic method of classification for parkinsonian variant of multiple system atrophy (MSA-P) and Idiopathic Parkinson's disease (IPD) in early to moderately advanced stages based on multimodal striatal alterations and identify the striatal neuromarkers for distinction. METHODS: 77 IPD and 75 MSA-P patients underwent 3.0 T multimodal MRI comprising susceptibility-weighted imaging, resting-state functional magnetic resonance imaging, T1-weighted imaging, and diffusion tensor imaging. Iron-radiomic features, volumes, functional and diffusion scalars of bilateral 10 striatal subregions were calculated and provided to the support vector machine for classification RESULTS: A combination of iron-radiomic features, function, diffusion, and volumetric measures optimally distinguished IPD and MSA-P in the testing dataset (accuracy 0.911 and area under the receiver operating characteristic curves [AUC] 0.927). The diagnostic performance further improved when incorporating clinical variables into the multimodal model (accuracy 0.934 and AUC 0.953). The most crucial factor for classification was the functional activity of the left dorsolateral putamen. CONCLUSION: The machine learning algorithm applied to multimodal striatal dysfunction depicted dorsal striatum and supervening prefrontal lobe and cerebellar dysfunction through the frontostriatal and cerebello-striatal connections and facilitated accurate classification between IPD and MSA-P. The dorsolateral putamen was the most valuable neuromarker for the classification.

Identifying and validating subtypes of Parkinson's disease based on multimodal MRI data via hierarchical clustering analysis.

Objective: We wished to explore Parkinson's disease (PD) subtypes by clustering analysis based on the multimodal magnetic resonance imaging (MRI) indices amplitude of low-frequency fluctuation (ALFF) and gray matter volume (GMV). Then, we analyzed the differences between PD subtypes. Methods: Eighty-six PD patients and 44 healthy controls (HCs) were recruited. We extracted ALFF and GMV according to the Anatomical Automatic Labeling (AAL) partition using Data Processing and Analysis for Brain Imaging (DPABI) software. The Ward linkage method was used for hierarchical clustering analysis. DPABI was employed to compare differences in ALFF and GMV between groups. Results: Two subtypes of PD were identified. The "diffuse malignant subtype" was characterized by reduced ALFF in the visual-related cortex and extensive reduction of GMV with severe impairment in motor function and cognitive function. The "mild subtype" was characterized by increased ALFF in the frontal lobe, temporal lobe, and sensorimotor cortex, and a slight decrease in GMV with mild impairment of motor function and cognitive function. Conclusion: Hierarchical clustering analysis based on multimodal MRI indices could be employed to identify two PD subtypes. These two PD subtypes showed different neurodegenerative patterns upon imaging.

Regular Periodic Surface Structures on Indium Tin Oxide Film Efficiently Fabricated by Femtosecond Laser Direct Writing with a Cylindrical Lens.

Regular laser-induced periodic surface structures (LIPSS) were efficiently fabricated on indium tin oxide (ITO) films by femtosecond laser direct writing with a cylindrical lens. It was found that randomly distributed nanoparticles and high spatial frequency LIPSSs (HSFL) formed on the surface after a small number of cumulative incident laser pulses per spot, and regular low spatial frequency LIPSSs (LSFL) appeared when more laser pulses accumulated. The mechanism of the transition was studied by real-time absorptance measurement and theoretical simulation. Results show that the interference between incident laser and surface plasmon polaritons (SPPs) excited by random surface scatterers facilitates the formation of prototype LSFLs, which in turn enhances light absorption and SPP excitation following laser pulses. The effects of scanning velocity and laser fluence on LSFL quality were discussed in detail. Moreover, large-area extremely regular LSFL with a diameter of 30 mm were efficiently fabricated on an ITO film by femtosecond laser direct writing with the cylindrical lens. The fabricated LSFLs on the ITO film demonstrate vivid structural color. During LSFL processing, the decrease of ITO film thickness leads to the increase of near-infrared optical transmittance.

Vesicle transport related protein Synaptotagmin-1 mediates paraquat transport to antagonize paraquat toxicity.

In this study, A549/PQ cells with moderate resistance to paraquat (PQ) were obtained by treating A549 cells with PQ, their growth rate was slowed down, the accumulation concentration of PQ and the levels of growth inhibition, injury and early apoptosis induced by PQ were significantly lower than those of parental A549 cells. Microarray screening and RT-qPCR detection found that Synaptotagmin-1 (SYT1) expression in drug-resistant cells was significantly increased, and PQ further enhanced its expression. After inhibiting SYT1 expression in A549/PQ cells, cell viability, intracellular PQ concentration and the expression of Bcl-2, SNAP25 and RAB26 were significantly reduced, while the mortality, early apoptosis rate and Bax expression were significantly increased. In vivo experiments also further showed that PQ promoted the expression of SYT1, SNAP25 and RAB26 in PQ-poisoned mice; when inhibiting SYT1 expression, PQ concentration in lung tissues was significantly increased, and the levels of lung injury and apoptosis were also significantly enhanced, while the expression of SNAP25 and RAB26 was significantly reduced. This indicates that PQ poisoning leads to compensatory up-regulation of vesicle transport related proteins such as SYT1 in vivo, thereby promoting PQ transmembrane transport, and then reducing the pulmonary accumulation of PQ and PQ-caused lung injury.

Surface birefringence of regular periodic surface structures produced on glass coated with an indium tin oxide film using a low-fluence femtosecond laser through a cylindrical lens.

Large-area regular laser-induced periodic surface structures (LIPSSs) with a birefringence effect were efficiently produced on a glass surface coated with an indium tin oxide (ITO) film, through irradiation by a femtosecond laser (800 nm, 50 fs, 3 mJ, 1 kHz) focused with a cylindrical lens. The laser fluence of 0.44 J/cm2 on the coated glass was only one-tenth of that on bare glass, which significantly reduced the thermal effect. Moreover, regular LIPSSs with a period as short as 100 nm could be produced efficiently. The retardance of the fabricated LIPSSs was measured to be up to 44 nm, which is eight times that of LIPSSs fabricated on bare glass. The mechanisms of such a large difference of retardance were studied by measuring the nanostructures and the concentration of In3+ ions on the cross section of nano-corrugated surface layer on bare glass and ITO-coated glass.

Gas6 attenuates lipopolysaccharide­induced TNF­α expression and apoptosis in H9C2 cells through NF­κB and MAPK inhibition via the Axl/PI3K/Akt pathway.

Therapeutic agents used to treat sepsis­induced cardiac dysfunction are designed to suppress tumor necrosis factor (TNF)­α release and inhibit cell apoptosis. Exogenous administration of growth arrest­specific 6 (Gas6) exerts several biological and pharmacological effects; however, the role of Gas6 in sepsis­induced myocardial dysfunction remains unclear. In this study, H9C2 cardiomyocytes were stimulated with LPS (10 µg/ml) to mimic septic cardiac dysfunction and Gas6 (100 ng/ml) was applied exogenously. Subsequently, mitogen­activated protein kinase (MAPK) and nuclear factor (NF)­κB activation, TNF­α expression, and apoptosis in the presence or absence of TP­0903 (15 nM) and Wortmannin (3 nM) were evaluated. The morphological alterations of H9C2 cells were visualized by phase­contrast microscopy. Cell viability was determined using the Cell Counting kit 8 assay and lactate dehydrogenase release, and TNF­α release was analyzed by ELISA analysis. Cell apoptosis was analyzed by flow cytometry and TUNEL assay. Nuclear morphological alterations were detected by Hoechst staining and caspase­3 activity was measured using biochemical methods. The expression levels of Bax and Bcl­2, and the phosphorylation and expression levels of Axl, Akt, IκB­α, p65, c­Jun N­terminal protein kinase (JNK), extracellular signal­regulated kinase (ERK) and p38 were determined by western blotting. Furthermore, immunofluorescence analysis was performed to visualize translocation of NF­κB p65. The results demonstrated that Gas6 suppressed TNF­α release and inhibited cell apoptosis, and attenuated nuclear factor (NF)­κB and mitogen­activated protein kinase (MAPK) activation via the Axl/PI3K/Akt pathway. Furthermore, the cardioprotective properties of Gas6 on the suppression of LPS­induced TNF­α release and apoptosis were abolished by treatment with TP­0903 (an Axl inhibitor) and Wortmannin (a PI3K inhibitor). Pretreatment with TP­0903 and Wortmannin abrogated the effects of Gas6 on phosphorylated­IκB­α, IκB­α, NF­κB, ERK1/2, JNK and p38 MAPK. These findings suggested that activation of Axl/PI3K/Akt signaling by Gas6 may inhibit LPS­induced TNF­α expression and apoptosis, as well as MAPK and NF­κB activation.

Crosstalk between Mitochondrial Fission and Oxidative Stress in Paraquat-Induced Apoptosis in Mouse Alveolar Type II Cells.

Paraquat (PQ), as a highly effective and nonselective herbicide, induces cell apoptosis through generation of superoxide anions which forms reactive oxygen species (ROS). Mitochondria, as regulators for cellular redox signaling, have been proved to play an important role in PQ-induced cell apoptosis. This study aimed to evaluate whether and how mitochondrial fission interacts with oxidative stress in PQ-induced apoptosis in mouse alveolar type II (AT-II) cells. Firstly, we demonstrated that PQ promoted apoptosis and release of cytochrome-c (Cyt-c). Furthermore, we showed that PQ broke down mitochondrial network, enhanced the expression of fission-related proteins, increased Drp1 mitochondrial translocation while decreased the expression of fusion-related proteins in AT-II cells. Besides, inhibiting mitochondrial fission using mdivi-1, a selective inhibitor of Drp1, markedly attenuated PQ-induced apoptosis, release of Cyt-c and the generation of ROS. These results indicate that mitochondrial fission involves in PQ-induced apoptosis. Further study demonstrated that antioxidant ascorbic acid inhibited Drp1 mitochondrial translocation, mitochondrial fission and attenuated PQ-induced apoptosis. Overall, our findings suggest that mitochondrial fission interplays with ROS in PQ-induced apoptosis in mouse AT-II cells and mitochondrial fission could serve as a potential therapeutic target in PQ poisoning.