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Widespread white matter (WM) injury is a hallmark feature of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, controversies about the mechanism of WM tract injury exist persistently. Excessive iron accumulation, frequently reported in CADASIL patients, might cause WM tract injury.To test the association between iron accumulation and WM tract injury in CADASIL patients.Retrospective.A total of 35 CADASIL patients (age = 50.4 ± 6.4, 62.9% female) and 48 healthy controls (age = 55.7 ± 8.0, 68.8% female).Diffusion-weighted spin-echo echo-planar sequence; enhanced susceptibility-weighted angiography (ESWAN) gradient echo sequence on a 3 T scanner.The phase images acquired by ESWAN were used to calculate quantitative susceptibility mapping (QSM). Iron accumulation was evaluated in deep gray matters using QSM. WM tract injury was quantified by diffusion metrics based on WM major tracts skeleton. We compared iron deposition between groups and analyzed the correlation between WM tract injury and iron deposition in regions showing significant differences from healthy controls. Exploratory analysis was carried out to investigate whether WM tract injury mediated the relationship between iron deposition and cognitive impairment evaluated by Mini-Mental State Examination (MMSE).General linear model (GLM), partial correlation, stepwise linear regression and mediation analysis were used. The threshold of statistical significance was set as p 0.05.Compared with healthy controls, CADASIL patients had significantly increased iron deposition in the caudate and putamen. Aberrant iron deposition in these two regions was significantly associated with decreased WM fractional anisotropy (FA) (caudate, r = -0.373； putamen, r = - 0.421), and increased radial diffusivity (RD) (caudate, r = 0.372; putamen, r = 0.386). Furthermore, WM tract injury mediated the relationship between iron deposition and cognitive impairment.Patients with CADASIL show increased iron deposition in the caudate and putamen that is correlated to WM tract injury, which may in turn mediate the association with cognitive impairment.2 TECHNICAL EFFICACY: Stage 2.

BACKGROUND Perivascular spaces (PVSs) are important component of the brain glymphatic system. While visual rating has been widely used to assess PVS, computational measures may have higher sensitivity for capturing PVS characteristics under disease conditions. PURPOSE To compute quantitative and morphological PVS features and to assess their associations with vascular risk factors and cerebral small vessel disease (CSVD). STUDY TYPE Prospective. POPULATION One hundred sixty-one middle-aged/later middle-aged subjects (age = 60.4 ± 7.3). SEQUENCE 3D T1-weighted, T2-weighted and T2-FLAIR sequences, and susceptibility-weighted multiecho gradient-echo sequence on a 3 T scanner. ASSESSMENT Automated PVS segmentation was performed on sub-millimeter T2-weighted images. Quantitative and morphological PVS features were calculated in white matter (WM) and basal ganglia (BG) regions, including volume, count, size, length (Lmaj ), width (Lmin ), and linearity. Visual PVS scores were also acquired for comparison. STATISTICAL TESTS Simple and multiple linear regression analyses were used to explore the associations among variables. RESULTS WM-PVS visual score and count were associated with hypertension (β = 0.161, P

BACKGROUND The degeneration of the corticospinal tract (CST) in chronic stroke has been widely described using diffusion tensor imaging and correlates with the extent of motor deficits. However, only a few studies have reported the early degeneration in the distal CST during the acute stage of stroke and pathological changes in the distal CST have not been described. PURPOSE To study the microstructural changes along the CST beyond the ischemic lesion in acute stroke using diffusion kurtosis imaging (DKI). STUDY TYPE Prospective. POPULATION In all, 48 patients (26 males, 22 females; mean age 58.27 ± 12.89 years) with acute ischemic stroke. SEQUENCE A DKI sequence with three b-values (0, 1000, and 2000 s/mm2 ) at 3.0T MRI. ASSESSMENT The kurtosis and tensor parameters were derived from DKI and were compared along the length of the CST beyond the ischemic lesion between the affected and unaffected hemispheres using both voxelwise and slicewise analysis. The degree of neurological deficits was evaluated using the National Institute of Health Stroke Score (NIHSS) and the Barthel index and the clinical outcome at 3 months was evaluated using a modified Rankin scale. STATISTICAL TESTS Paired t-tests, a linear mixed model, and multivariate linear regression. RESULTS Voxelwise analysis demonstrated increased mean kurtosis, increased axial kurtosis, and decreased axial diffusivity in the affected CST, which were seen only at the level of the cerebral peduncle (all corrected P

Modern pharmacological studies have shown that Fructus Tribuli can improve sexual function and treat cardiovascular diseases. In this study, we focused on comparing the pharmacokinetics of crude Fructus Tribuli (CFT) and stir-fried Fructus Tribuli (SFT) to further clarify the changes in chemical composition in vivo. The quantitation of six analytes was performed in a triple quadrupole mass spectrometer using the multiple reaction monitoring mode. Separation was performed on a Halo® C18 column using 0.05% formic acid and 5 μmol/L sodium formate in water, and 0.05% formic acid and 5 μmol/L sodium formate in acetonitrile as the mobile phase. The selectivity, precision, accuracy, extraction recovery, matrix effect and stability of the method were fully validated. Compared with the crude group, the parameters Cmax and AUC0-t of terrestroside B and terrestrosin K increased significantly (P < 0.05), but the Cmax and AUC0-t of polianthoside D, terrestrinin D, tribuluside A and terrestrosin D were decreased, terrestrosin D being especially decreased (P < 0.05), after oral administration of SFT extract. These results showed that the developed method was suitable for pharmacokinetic analysis of the six steroid saponins of CFT and SFT in rat plasma, and can be used to facilitate future clinical studies.

This study aimed to examine the proliferation of and secretion by rat ovarian granulosa cells (GCs) treated with mono-(2-ethylhexyl) phthalate (MEHP). Ovarian GCs were incubated with MEHP at concentration of 0, 25, 50, 100, and 200 µM for 24 hr. Cell viability was determined using the MTT Cell Proliferation Assay. Progesterone and estradiol production was evaluated by radioimmunoassay (RIA) and the expression of FSHR, PR, and ER was measured by immunocytochemistry. StAR, P450scc, 3β-HSD, 17β-HSD, and P450 arom mRNA levels were determined by RT-PCR. MEHP markedly attenuated proliferation of GCs, increased expression of sex hormone receptors and key enzymes in progesterone production, and stimulated steroid hormone secretion. The result of these analyses demonstrates that MEHP exposure of GCs may have effects on rat ovarian functions.

Using (hetero)aryl fluorosulfonates as versatile electrophiles, facile on‐DNA cross‐coupling reactions of Suzuki, Sonogashira, and Buchwald are reported here. Notably, all of these reactions show excellent functional group tolerance, mild reaction conditions (relative low temperature and open to air), rich heterocyclic coupling partners, and more importantly, DNA‐compatibility. Thus, these new reactions based on efficient formation of C(sp2)‐C(sp2), C(sp2)‐C(sp), and C(sp2)‐N bonds are highly amenable to synthesis of DNA‐encoded libraries with great molecular diversity., Mild on‐DNA Suzuki, Sonogashira, and Buchwald cross‐coupling reactions use (hetero)aryl fluorosulfonates as versatile electrophiles.

Engineering C4 photosynthesis into rice has been considered a promising strategy to increase photosynthesis and yield. A question that remains to be answered is whether expressing a C4 metabolic cycle into a C3 leaf structure and without removing the C3 background metabolism improves photosynthetic efficiency. To explore this question, we developed a 3D reaction diffusion model of bundle-sheath and connected mesophyll cells in a C3 rice leaf. Our results show that integrating a C4 metabolic pathway into rice leaves with a C3 metabolism and mesophyll structure may lead to an improved photosynthesis under current ambient CO2 concentration. We analysed a number of physiological factors that influence the CO2 uptake rate, which include the chloroplast surface area exposed to intercellular air space, bundle-sheath cell wall thickness, bundle-sheath chloroplast envelope permeability, Rubisco concentration and the energy partitioning between C3 and C4 cycles. Among these, partitioning of energy between C3 and C4 photosynthesis and the partitioning of Rubisco between mesophyll and bundle-sheath cells are decisive factors controlling photosynthetic efficiency in an engineered C3 -C4 leaf. The implications of the results for the sequence of C4 evolution are also discussed.

Hepatic insulin resistance, defined as a diminished ability of hepatocytes to respond to the action of insulin, plays an important role in the development of type 2 diabetes and metabolic syndrome. Aberrant expression of mmu-miR-152-3p (miR-152) is related to the pathogenesis of tumors such as hepatitis B virus related hepatocellular carcinoma. However, the role of miR-152 in hepatic insulin resistance remains unknown. In the present study, we identified the potential role of miR-152 in regulating hepatic glycogenesis. The expression of miR-152 and the level of glycogen were significantly downregulated in the liver of db/db mice and mice fed a high fat diet. In vivo and in vitro results suggest that inhibition of miR-152 expression induced impaired glycogenesis in hepatocytes. Interestingly, miR-152 expression, glycogen synthesis and protein kinase B/glycogen synthase kinase (AKT/GSK) pathway activation were significantly decreased in the liver of mice injected with 16 μg·mL(-1) interleukin 6 (IL-6) by pumps for 7 days and in NCTC 1469 cells treated with 10 ng·mL(-1) IL-6 for 24 h. Moreover, hepatic overexpression of miR-152 rescued IL-6-induced impaired glycogenesis. Finally, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-152 to mediate hepatic glycogen synthesis. Our findings provide mechanistic insight into the effects of miR-152 on the regulation of the AKT/GSK pathway and the synthesis of glycogen in hepatocytes. Downregulated miR-152 induced impaired hepatic glycogenesis by targeting PTEN. PTEN participated in miR-152-mediated glycogenesis in hepatocytes via regulation of the AKT/GSK pathway.

Recently, it is implicated that aberrant expression of microRNAs (miRs) is associated with insulin resistance. However, the role of miR‐17 family in hepatic insulin resistance and its underlying mechanisms remain unknown. In this study, we provided mechanistic insight into the effects of miR‐20a‐5p, a member of miR‐17 family, on the regulation of AKT/GSK pathway and glycogenesis in hepatocytes. MiR‐20a‐5p was down‐regulated in the liver of db/db mice, and NCTC1469 cells and Hep1‐6 cells treated with high glucose, accompanied by reduced glycogen content and impaired insulin signalling. Notably, inhibition of miR‐20a‐5p significantly reduced glycogen synthesis and AKT/GSK activation, whereas overexpression of miR‐20a‐5p led to elevated glycogenesis and activated AKT/GSK signalling pathway. In addition, miR‐20a‐5p mimic could reverse high glucose‐induced impaired glycogenesis and AKT/GSK activation in NCTC1469 and Hep1‐6 cells. P63 was identified as a target of miR‐20a‐5p by bioinformatics analysis and luciferase reporter assay. Knockdown of p63 in the NCTC1469 cells and the Hep1‐6 cells by transfecting with siRNA targeting p63 could increase glycogen content and reverse miR‐20a‐5p inhibition‐induced reduced glycogenesis and activation of AKT and GSK, suggesting that p63 participated in miR‐20a‐5p‐mediated glycogenesis in hepatocytes. Moreover, our results indicate that p63 might directly bind to p53, thereby regulating PTEN expression and in turn participating in glycogenesis. In conclusion, we found novel evidence suggesting that as a member of miR‐17 family, miR‐20a‐5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression.