Scalable, cell type-selective, AAV-based in vivo CRISPR screening in the mouse brain.

CRISPR-based genetic screening directly in mammalian tissues in vivo is challenging due to the need for scalable, cell-type selective delivery and recovery of guide RNA libraries. We developed an in vivo adeno-associated virus-based and Cre recombinase-dependent workflow for cell type-selective CRISPR interference screening in mouse tissues. We demonstrate the power of this approach by identifying neuron-essential genes in the mouse brain using a library targeting over 2000 genes.

The Value of Magnetic Resonance Imaging Histograms in the Preoperative Differential Diagnosis of Endometrial Stromal Sarcoma and Degenerative Hysteromyoma.

Objective: The present study aimed to explore the application value of magnetic resonance imaging (MRI) histograms with multiple sequences in the preoperative differential diagnosis of endometrial stromal sarcoma (ESS) and degenerative hysteromyoma (DH). Methods: The clinical and preoperative MRI data of 20 patients with pathologically confirmed ESS and 24 patients with pathologically confirmed DH were retrospectively analyzed, forming the two study groups. Mazda software was used to select the MRI layer with the largest tumor diameter in T2WI, the apparent diffusion coefficient (ADC), and enhanced T1WI (T1CE) images. The region of interest (ROI) was outlined for gray-scale histogram analysis. Nine parameters-the mean, variance, kurtosis, skewness, 1st percentile, 10th percentile, 50th percentile, 90th percentile, and 99th percentile-were obtained for intergroup analysis, and the receiver operating curves (ROCs) were plotted to analyze the differential diagnostic efficacy for each parameter. Results: In the T2WI histogram, the differences between the two groups in seven of the parameters (mean, skewness, 1st percentile, 10th percentile, 50th percentile, 90th percentile, and 99th percentile) were statistically significant (P < 0.05). In the ADC histogram, the differences between the two groups in three of the parameters (skewness, 10th percentile, and 50th percentile) were statistically significant (P < 0.05). In the T1CE histogram, no significant differences were found between the two groups in any of the parameters (all P > 0.05). Of the nine parameters, the 50th percentile was found to have the best diagnostic efficacy. In the T2WI histogram, ROC curve analysis of the 50th percentile yielded the best area under the ROC curve (AUC; 0.742), sensitivity of 70%, and specificity of 83.3%. In the ADC histogram, ROC curve analysis of the 50th percentile yielded the best area under the ROC curve (AUC; 0.783), sensitivity of 81%, and specificity of 76.9%. Conclusion: The parameters of the mean, 10th percentile and 50th percentile in the T2WI histogram have good diagnostic efficacy, providing new methods and ideas for clinical diagnosis.

Region-specific distribution of ß-amyloid peptide and cytokine expression in TgCRND8 mice.

Alzheimer's disease (AD) is a multifactorial disease that results in progressive neurodegeneration. Brain regions are differentially affected in AD. There is also an age-dependent effect on amyloid-beta peptide (Aß) accumulation and neuroinflammation as disease progresses. In the TgCRND8 APP transgenic mouse model, levels of Aß species and cytokines were examined as a function of brain region and age. A temporal sequence was observed whereby Aß accumulation is followed by expression of IL-1ß and eventually, of CXCL1, in the hippocampus and olfactory bulb but not the cortex. We have shown for the first time, in an APP mouse model, age and regional differences in Aß accumulation and cytokine expression.