Magnetic Resonance Imaging Combined with Histological Techniques for Dynamic Assessment of Cytotoxic Edema after Cerebral Ischemia-Reperfusion Injury.

BACKGROUND: Reperfusion therapy after ischemic cerebral stroke may cause cerebral ischemia-reperfusion injury (CIRI), and cerebral edema is an important factor that may aggravate CIRI. Our study aimed to dynamically monitor the development of early cytotoxic edema after CIRI by magnetic resonance imaging (MRI) and to validate it using multiple histological imaging methods. METHODS: Male Sprague Dawley rats were divided into sham and CIRI groups. T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)-MRI scans were performed in the sham and CIRI groups after reperfusion. Relative apparent diffusion coefficient (rADC) values were calculated and the midline shift (MLS) was measured. A series of histological detection techniques were performed to observe changes in the cerebral cortex and striatum of CIRI rats. Correlation analysis of rADC values with aquaporin-4 (AQP4) and sodium-potassium-chloride cotransport protein 1 (Na+-K+-2Cl-- cotransporter 1; NKCC1) was performed. RESULTS: rADC values began to increase and reached a relatively low value in the cerebral cortex and striatum at 24 h after reperfusion, and the MLS reached relatively high values at 24 h after reperfusion (all p < 0.05). Hematoxylin-eosin (HE) staining showed that the nerve cells in the cortex and striatum of the sham group were regular in morphology and neatly arranged, and in the CIRI-24 h group were irregular, disorganized, and loosely structured. Using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, the number of TUNEL+ cells in the ischemic cortex and striatum in CIRI-24 h group was shown to increase significantly compared with the sham group (p < 0.05). Transmission electron microscopy showed that the perivascular astrocytic foot processes were swollen in the cortex and striatum of the CIRI-24 h group. Pearson correlation analysis demonstrated that rADC values were negatively correlated with the number of anti-glial fibrillary acidic protein (GFAP)+AQP4+ and GFAP+NKCC1+ cells of the CIRI rats. CONCLUSIONS: MRI combined with histological techniques can dynamically assess cytotoxic edema after CIRI, in a manner that is clear and intuitive for scientific researchers and clinicians, and provides a scientific basis for the application of MRI techniques for monitoring the dynamic progress of CIRI.

Effects of Sport Stacking on Neuropsychological, Neurobiological, and Brain Function Performances in Patients With Mild Alzheimer's Disease and Mild Cognitive Impairment: A Randomized Controlled Trial.

Objective: To investigate the effects of sport stacking on the overall cognition and brain function in patients with mild Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: A single-blind randomized controlled design was performed using sport stacking for 30 min, 5 days/week for 12 weeks. Forty-eight subjects with mild AD or MCI were randomly divided into the sport stacking group (T-mAD = 12, T-MCI = 12) and the active control group (C-mAD = 11, C-MCI = 13). Auditory Verbal Learning Test (AVLT), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), Geriatric Depression Scale (GDS-30), and Pittsburgh Sleep Quality Index (PSQI) were performed, the level of amyloid ß-protein-40 (Aß-40), Aß-42, brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1(IGF-1), tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and soluble trigger receptor expressed on myeloid cells 2 (sTREM2) in plasma were tested, and brain functional connectivity in resting state and activation under finger movement task were analyzed by functional near-infrared spectroscopy (fNIRS). Results: Thirty-nine patients completed the trial. After 4 weeks, we found a significant increase in AVLT score in T-MCI (6.36 ± 5.08 vs. -1.11 ± 4.23, p = 0.004), and T-mAD group (4.60 ± 4.77 vs. -0.11 ± 2.89, p = 0.039). After 12 weeks, there was a significantly improved in AVLT (9.64 ± 4.90 vs. -0.33 ± 6.10, p = 0.002) and ADCS-ADL (3.36 ± 3.59 vs. -1.89 ± 2.71, p = 0.003) in T-MCI. There was a significant improvement in AVLT (5.30 ± 5.42 vs. 0.44 ± 2.40) in T-mAD (p < 0.05). Plasma levels of BDNF were upregulated in both T-MCI and T-mAD, and IGF-1 increased in T-MCI (P < 0.05) compared to the control groups. The functional connectivity in MCI patients between DLPFC.R and SCA.R, SMA.L, and SCA.R was decreased. In contrast, in mAD patients, the brain regional function connection was increased between DLPFC.R and Broca's.L. The activation of channel 36 located in the left primary somatosensory cortex was significantly increased after 12-week training, which was correlated with the improved AVLT and the increase of BDNF. Conclusion: Our findings suggested that sport stacking is effective for patients with MCI and mild AD, possibly through increasing the expression of neuroprotective growth factors and enhancing neural plasticity to improve neurocognitive performance. Clinical Trial Registration: https://www.ClinicalTrials.gov, ChiCTR.org.cn, identifier: ChiCTR-2100045980.

Sustained Drug Release From Liposomes for the Remodeling of Systemic Immune Homeostasis and the Tumor Microenvironment.

Myeloid Derived Suppressor Cells (MDSCs) play important roles in constituting the immune suppressive environment promoting cancer development and progression. They are consisted of a heterogeneous population of immature myeloid cells including polymorphonuclear MDSC (PMN-MDSC) and monocytes MDSC (M-MDSC) that are found in both the systemic circulation and in the tumor microenvironment (TME). While previous studies had shown that all-trans retinoic acid (ATRA) could induce MDSC differentiation and maturation, the very poor solubility and fast metabolism of the drug limited its applications as an immune-modulator for cancer immunotherapy. We aimed in this study to develop a drug encapsulated liposome formulation L-ATRA with sustained release properties and examined the immuno-modulation effects. We showed that the actively loaded L-ATRA achieved stable encapsulation and enabled controlled drug release and accumulation in the tumor tissues. In vivo administration of L-ATRA promoted the remodeling of the systemic immune homeostasis as well as the tumor microenvironment. They were found to promote MDSCs maturation into DCs and facilitate immune responses against cancer cells. When used as a single agent treatment, L-ATRA deterred tumor growth, but only in immune-competent mice. In mice with impaired immune functions, L-ATRA at the same dose was not effective. When combined with checkpoint inhibitory agents, L-ATRA resulted in greater anti-cancer activities. Thus, L-ATRA may present a new IO strategy targeting the MDSCs that needs be further explored for improving the immunotherapy efficacy in cancer.

Professional chess expertise modulates whole brain functional connectivity pattern homogeneity and couplings.

Previous studies have revealed changed functional connectivity patterns between brain areas in chess players using resting-state functional magnetic resonance imaging (rs-fMRI). However, how to exactly characterize the voxel-wise whole brain functional connectivity pattern changes in chess players remains unclear. It could provide more convincing evidence for establishing the relationship between long-term chess practice and brain function changes. In this study, we employed newly developed whole brain functional connectivity pattern homogeneity (FcHo) method to identify the voxel-wise changes of functional connectivity patterns in 28 chess master players and 27 healthy novices. Seed-based functional connectivity analysis was used to identify the alteration of corresponding functional couplings. FcHo analysis revealed significantly increased whole brain functional connectivity pattern similarity in anterior cingulate cortex (ACC), anterior middle temporal gyrus (aMTG), primary visual cortex (V1), and decreased FcHo in thalamus and precentral gyrus in chess players. Resting-state functional connectivity analyses identified chess players showing decreased functional connections between V1 and precentral gyrus. Besides, a linear support vector machine (SVM) based classification achieved an accuracy of 85.45%, a sensitivity of 85.71% and a specificity of 85.19% to differentiate chess players from novices by leave-one-out cross-validation. Finally, correlation analyses revealed that the mean FcHo values of thalamus were significantly negatively correlated with the training time. Our findings provide new evidences for the important roles of ACC, aMTG, V1, thalamus and precentral gyrus in chess players. The findings also indicate that long-term professional chess training may enhance the semantic and episodic processing, efficiency of visual-motor transformation, and cognitive ability.

Altered Intrinsic and Casual Functional Connectivities of the Middle Temporal Visual Motion Area Subregions in Chess Experts.

An outstanding chess player needs to accumulate massive visual and spatial information for chess configurations. Visual motion area (MT) is considered as a brain region specialized for visual motion perception and visuospatial attention processing. However, how long-term chess training shapes the functional connectivity patterns of MT, especially its functional subregions, has rarely been investigated. In our study, using resting-state functional connectivity (RSFC) and Granger causality analysis (GCA), we studied the changed functional couplings of MT subregions between 28 chess master players and 27 gender- and age-matched healthy novices to reveal the neural basis of long-term professional chess training. RSFC analysis identified decreased functional connections between right dorsal-anterior subregion (CI1.R) and left angular gyrus, and increased functional connections between right ventral-anterior MT subregion (CI2.R) and right superior temporal gyrus in chess experts. Moreover, GCA analyses further found increased mutual interactions of left angular gyrus and CI1.R in chess experts compared to novice players. These findings demonstrate that long-term professional chess training could enhance spatial perception and reconfiguration and semantic processing efficiency for superior performance.

Diagnostic value of two dimensional shear wave elastography combined with texture analysis in early liver fibrosis.

BACKGROUND: Staging diagnosis of liver fibrosis is a prerequisite for timely diagnosis and therapy in patients with chronic hepatitis B. In recent years, ultrasound elastography has become an important method for clinical noninvasive assessment of liver fibrosis stage, but its diagnostic value for early liver fibrosis still needs to be further improved. In this study, the texture analysis was carried out on the basis of two dimensional shear wave elastography (2D-SWE), and the feasibility of 2D-SWE plus texture analysis in the diagnosis of early liver fibrosis was discussed. AIM: To assess the diagnostic value of 2D-SWE combined with textural analysis in liver fibrosis staging. METHODS: This study recruited 46 patients with chronic hepatitis B. Patients underwent 2D-SWE and texture analysis; Young's modulus values and textural patterns were obtained, respectively. Textural pattern was analyzed with regard to contrast, correlation, angular second moment (ASM), and homogeneity. Pathological results of biopsy specimens were the gold standard; comparison and assessment of the diagnosis efficiency were conducted for 2D-SWE, texture analysis and their combination. RESULTS: 2D-SWE displayed diagnosis efficiency in early fibrosis, significant fibrosis, severe fibrosis, and early cirrhosis (AUC > 0.7, P < 0.05) with respective AUC values of 0.823 (0.678-0.921), 0.808 (0.662-0.911), 0.920 (0.798-0.980), and 0.855 (0.716-0.943). Contrast and homogeneity displayed independent diagnosis efficiency in liver fibrosis stage (AUC > 0.7, P < 0.05), whereas correlation and ASM showed limited values. AUC of contrast and homogeneity were respectively 0.906 (0.779-0.973), 0.835 (0.693-0.930), 0.807 (0.660-0.910) and 0.925 (0.805-0.983), 0.789 (0.639-0.897), 0.736 (0.582-0.858), 0.705 (0.549-0.883) and 0.798 (0.650-0.904) in four liver fibrosis stages, which exhibited equivalence to 2D-SWE in diagnostic efficiency (P > 0.05). Combined diagnosis (PRE) displayed diagnostic efficiency (AUC > 0.7, P < 0.01) for all fibrosis stages with respective AUC of 0.952 (0.841-0.994), 0.896 (0.766-0.967), 0.978 (0.881-0.999), 0.947 (0.835-0.992). The combined diagnosis showed higher diagnosis efficiency over 2D-SWE in early liver fibrosis (P < 0.05), whereas no significant differences were observed in other comparisons (P > 0.05). CONCLUSION: Texture analysis was capable of diagnosing liver fibrosis stage, combined diagnosis had obvious advantages in early liver fibrosis, liver fibrosis stage might be related to the hepatic tissue hardness distribution.

Reduced Graphene Oxide-Based Ordered Macroporous Films on a Curved Surface: General Fabrication and Application in Gas Sensors.

A new general method for the fabrication of a reduced graphene oxide (rGO)-based ordered monolayer macroporous film composed of a layer of closely arranged pores is introduced. Assisted by the polystyrene microsphere monolayer colloid crystal by a simple solution-heated method, pure rGO, rGO-SnO2, rGO-Fe2O3, and rGO-NiO composite monolayer ordered porous films were examplarily constructed on the curved surface of a ceramic tube widely used in gas sensors. The rGO-oxide composite porous films could exhibit much better sensing performances than those of the corresponding pure oxide films and the composite films without the ordered porous structures in detecting ethanol gas. The enhancement mechanisms induced by distinctive rGO-oxide heterojunctions and porous structures as well as the effects of the rGO content and the pore-size on the sensitivity of the composite films were systematically analyzed and discussed. This study opens up a kind of construction method for an rGO-based composite film gas sensor with uniform surface structures and high performance.

Fabrication of SnO2-reduced graphite oxide monolayer-ordered porous film gas sensor with tunable sensitivity through ultra-violet light irradiation.

A new graphene-based composite structure, monolayer-ordered macroporous film composed of a layer of orderly arranged macropores, was reported. As an example, SnO2-reduced graphite oxide monolayer-ordered macroporous film was fabricated on a ceramic tube substrate under the irradiation of ultra-violet light (UV), by taking the latex microsphere two-dimensional colloid crystal as a template. Graphite oxide sheets dispersed in SnSO4 aqueous solution exhibited excellent affinity with template microspheres and were in situ incorporated into the pore walls during UV-induced growth of SnO2. The growing and the as-formed SnO2, just like other photocatalytic semiconductor, could be excited to produce electrons and holes under UV irradiation. Electrons reduced GO and holes adsorbed corresponding negative ions, which changed the properties of the composite film. This film was directly used as gas-sensor and was able to display high sensitivity in detecting ethanol gas. More interestingly, on the basis of SnO2-induced photochemical behaviours, this sensor demonstrated tunable sensitivity when UV irradiation time was controlled during the fabrication process and post in water, respectively. This study provides efficient ways of conducting the in situ fabrication of a semiconductor-reduced graphite oxide film device with uniform surface structure and controllable properties.