Deep learning-assisted diagnosis of large vessel occlusion in acute ischemic stroke based on four-dimensional computed tomography angiography.

Purpose: To develop deep learning models based on four-dimensional computed tomography angiography (4D-CTA) images for automatic detection of large vessel occlusion (LVO) in the anterior circulation that cause acute ischemic stroke. Methods: This retrospective study included 104 LVO patients and 105 non-LVO patients for deep learning models development. Another 30 LVO patients and 31 non-LVO patients formed the time-independent validation set. Four phases of 4D-CTA (arterial phase P1, arterial-venous phase P2, venous phase P3 and late venous phase P4) were arranged and combined and two input methods was used: combined input and superimposed input. Totally 26 models were constructed using a modified HRNet network. Assessment metrics included the areas under the curve (AUC), accuracy, sensitivity, specificity and F1 score. Kappa analysis was performed to assess inter-rater agreement between the best model and radiologists of different seniority. Results: The P1 + P2 model (combined input) had the best diagnostic performance. In the internal validation set, the AUC was 0.975 (95%CI: 0.878-0.999), accuracy was 0.911, sensitivity was 0.889, specificity was 0.944, and the F1 score was 0.909. In the time-independent validation set, the model demonstrated consistently high performance with an AUC of 0.942 (95%CI: 0.851-0.986), accuracy of 0.902, sensitivity of 0.867, specificity of 0.935, and an F1 score of 0.901. The best model showed strong consistency with the diagnostic efficacy of three radiologists of different seniority (k = 0.84, 0.80, 0.70, respectively). Conclusion: The deep learning model, using combined arterial and arterial-venous phase, was highly effective in detecting LVO, alerting radiologists to speed up the diagnosis.

G-quadruplex is involved in the regulation of BmSGF1 expression in the Silkworm, Bombyx mori.

Advanced DNA structures, such as the G-quadruplex (G4) and the i-motif, are widely but not randomly present in the genomes of many organisms. A G4 structure was identified in the promoter of the silk gland factor-1 gene (SGF1), which is the main regulatory gene for silk production in Bombyx mori. In this study, a BmSGF1 G4-/- homozygous mutant was generated with the G4 sequence knocked out. The promoter activity of BmSGF1 was lowered in the BmSGF1 G4-/- mutant. Pyridostatin (PDS) stabilized the G4 structure and increased the promoter activity of BmSGF1, whereas anti-sense oligonucleotide (ASO) complementary to the G4 sequence suppressed the promoter activity of BmSGF1. Compared with wild-type larvae, the deletion of the BmSGF1 G4 structure decreased both the expression of BmSGF1 and the fibroin heavy chain gene BmFib-H in the posterior silk gland and the weight of the cocoons. Overall, these results suggest that the promoter G4 structure of BmSGF1 participates in the transcription regulation of the BmSGF1 gene in the silkworm.

Comparison of diffusion tensor imaging (DTI) tissue characterization parameters in white matter tracts of patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD).

OBJECTIVE: To investigate the microstructural properties of T2 lesion and normal-appearing white matter (NAWM) in 20 white matter tracts between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) and correlations between the tissue damage and clinical variables. METHODS: The white matter (WM) compartment of the brain was segmented for 56 healthy controls (HC), 48 patients with MS, and 38 patients with NMOSD, and for the patients further subdivided into T2 lesion and NAWM. Subsequently, the diffusion tensor imaging (DTI) tissue characterization parameters of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared for 20 principal white matter tracts. The correlation between tissue damage and clinical variables was also investigated. RESULTS: The higher T2 lesion volumes of 14 fibers were shown in MS compared to NMOSD. MS showed more microstructure damage in 13 fibers of T2 lesion, but similar microstructure in seven fibers compared to NMOSD. MS and NMOSD had microstructure damage of NAWM in 20 fibers compared to WM in HC, with more damage in 20 fibers in MS compared to NMOSD. MS patients showed higher correlation between the microstructure of T2 lesion areas and NAWM. The T2 lesion microstructure damage was correlated with duration and impaired cognition in MS. CONCLUSIONS: Patients with MS and NMOSD show different patterns of microstructural damage in T2 lesion and NAWM areas. The prolonged disease course of MS may aggravate the microstructural damage, and the degree of microstructural damage is further related to cognitive impairment. CLINICAL RELEVANCE STATEMENT: Microstructure differences between T2 lesion areas and normal-appearing white matter help distinguish multiple sclerosis and neuromyelitis optica spectrum disorder. In multiple sclerosis, lesions rather than normal-appearing white matter should be a concern, because the degree of lesion severity correlated both with normal-appearing white matter damage and cognitive impairment. KEY POINTS: • Multiple sclerosis and neuromyelitis optica spectrum disorder have different damage patterns in T2 lesion and normal-appearing white matter areas. • The microstructure damage of normal-appearing white matter is correlated with the microstructure of T2 lesion in multiple sclerosis and neuromyelitis optica spectrum disorder. • The microstructure damage of T2 lesion in multiple sclerosis is correlated with duration and cognitive impairment.

U-fiber diffusion kurtosis and susceptibility characteristics in relapsing-remitting multiple sclerosis may be related to cognitive deficits and neurodegeneration.

OBJECTIVES: To evaluate the diffusion kurtosis and susceptibility change in the U-fiber region of patients with relapsing-remitting multiple sclerosis (pwRRMS) and their correlations with cognitive status and degeneration. MATERIALS AND METHODS: Mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), kurtosis fractional anisotropy (KFA), and the mean relative quantitative susceptibility mapping (mrQSM) values in the U-fiber region were compared between 49 pwRRMS and 48 healthy controls (HCs). The U-fiber were divided into upper and deeper groups based on the location. The whole brain volume, gray and white matter volume, and cortical thickness were obtained. The correlations between the mrQSM values, DKI-derived metrics in the U-fiber region and clinical scale scores, brain morphologic parameters were further investigated. RESULTS: The decreased MK, AK, RK, KFA, and increased mrQSM values in U-fiber lesions (p < 0.001, FDR corrected), decreased RK, KFA, and increased mrQSM values in U-fiber non-lesions (p = 0.034, p < 0.001, p < 0.001, FDR corrected) were found in pwRRMS. There were differences in DKI-derived metrics and susceptibility values between the upper U-fiber region and the deeper one for U-fiber non-lesion areas of pwRRMS and HCs (p < 0.05), but not for U-fiber lesions in DKI-derived metrics. The DKI-derived metrics and susceptibility values were widely related with cognitive tests and brain atrophy. CONCLUSION: RRMS patients show abnormal diffusion kurtosis and susceptibility characteristics in the U-fiber region, and these underlying tissue abnormalities are correlated with cognitive deficits and degeneration. CLINICAL RELEVANCE STATEMENT: The macroscopic and microscopic tissue damages of U-fiber help to identify cognitive impairment and brain atrophy in multiple sclerosis and provide underlying pathophysiological mechanism. KEY POINTS: • Diffusion kurtosis and susceptibility changes are present in the U-fiber region of multiple sclerosis. • There are gradients in diffusion kurtosis and susceptibility characteristics in the U-fiber region. • Tissue damages in the U-fiber region are correlated with cognitive impairment and brain atrophy.

c-Jun as a one-way valve at the naive to primed interface.

BACKGROUND: c-Jun is a proto-oncogene functioning as a transcription factor to activate gene expression under many physiological and pathological conditions, particularly in somatic cells. However, its role in early embryonic development remains unknown. RESULTS: Here, we show that c-Jun acts as a one-way valve to preserve the primed state and impair reversion to the naïve state. c-Jun is induced during the naive to primed transition, and it works to stabilize the chromatin structure and inhibit the reverse transition. Loss of c-Jun has surprisingly little effect on the naïve to primed transition, and no phenotypic effect on primed cells, however, in primed cells the loss of c-Jun leads to a failure to correctly close naïve-specific enhancers. When the primed cells are induced to reprogram to a naïve state, these enhancers are more rapidly activated when c-Jun is lost or impaired, and the conversion is more efficient. CONCLUSIONS: The results of this study indicate that c-Jun can function as a chromatin stabilizer in primed EpiSCs, to maintain the epigenetic cell type state and act as a one-way valve for cell fate conversions.

Deep Medullary Vein and MRI Markers Were Related to Cerebral Hemorrhage Subtypes.

BACKGROUND: To explore the performance of deep medullary vein (DMV) and magnetic resonance imaging (MRI) markers in different intracerebral hemorrhage (ICH) subtypes in patients with cerebral small vessel disease (CSVD). METHODS: In total, 232 cases of CSVD with ICH were included in this study. The clinical and image data were retrospectively analyzed. Patients were divided into hypertensive arteriopathy (HTNA)-related ICH, cerebral amyloid angiopathy (CAA)-related ICH, and mixed ICH groups. The DMV score was determined in the cerebral hemisphere contralateral to the ICH. RESULTS: The DMV score was different between the HTNA-related and mixed ICH groups (p < 0.01). The MRI markers and CSVD burden score were significant among the ICH groups (p < 0.05). Compared to mixed ICH, HTNA-related ICH diagnosis was associated with higher deep white matter hyperintensity (DWMH) (OR: 0.452, 95% CI: 0.253-0.809, p < 0.05) and high-degree perivascular space (PVS) (OR: 0.633, 95% CI: 0.416-0.963, p < 0.05), and CAA-related ICH diagnosis was associated with increased age (OR: 1.074; 95% CI: 1.028-1.122, p = 0.001). The DMV score correlated with cerebral microbleed (CMB), PVS, DWMH, periventricular white matter hyperintensity (PWMH), and CSVD burden score (p < 0.05) but not with lacuna (p > 0.05). Age was an independent risk factor for the severity of DMV score (OR: 1.052; 95% CI: 0.026-0.076, p < 0.001). CONCLUSION: DMV scores, CSVD markers, and CSVD burden scores were associated with different subtypes of ICH. In addition, DMV scores were associated with the severity of CSVD and CSVD markers.

Partial inhibition of class III PI3K VPS-34 ameliorates motor aging and prolongs health span.

Global increase of life expectancy is rarely accompanied by increased health span, calling for a greater understanding of age-associated behavioral decline. Motor independence is strongly associated with the quality of life of elderly people, yet the regulators for motor aging have not been systematically explored. Here, we designed a fast and efficient genome-wide screening assay in Caenorhabditis elegans and identified 34 consistent genes as potential regulators of motor aging. Among the top hits, we found VPS-34, the class III phosphatidylinositol 3-kinase that phosphorylates phosphatidylinositol (PI) to phosphatidylinositol 3-phosphate (PI(3)P), regulates motor function in aged but not young worms. It primarily functions in aged motor neurons by inhibiting PI(3)P-PI-PI(4)P conversion to reduce neurotransmission at the neuromuscular junction (NMJ). Genetic and pharmacological inhibition of VPS-34 improve neurotransmission and muscle integrity, ameliorating motor aging in both worms and mice. Thus, our genome-wide screening revealed an evolutionarily conserved, actionable target to delay motor aging and prolong health span.

One-day thermal regime extends the lifespan in Caenorhabditis elegans.

Environmental factors, including temperature, can modulate an animal's lifespan. However, their underlying mechanisms remain largely undefined. We observed a profound effect of temperature on the aging of Caenorhabditis elegans (C. elegans) by performing proteomic analysis at different time points (young adult, middle age, and old age) and temperature conditions (20 °C and 25 °C). Importantly, although at the higher temperature, animals had short life spans, the shift from 20 °C to 25 °C for one day during early adulthood was beneficial for protein homeostasis since; it decreased protein synthesis and increased degradation. Consistent with our findings, animals who lived longer in the 25 °C shift were also more resistant to high temperatures along with oxidative and UV stresses. Furthermore, the lifespan extension by the 25 °C shift was mediated by three important transcription factors, namely FOXO/DAF-16, HSF-1, and HIF-1. We revealed an unexpected and complicated mechanism underlying the effects of temperature on aging, which could potentially aid in developing strategies to treat age-related diseases. Our data are available in ProteomeXchange with the identifier PXD024916.

Enlarged choroid plexus related to cortical atrophy in multiple sclerosis.

OBJECTIVES: To investigate the correlation between choroid plexus volume and whole brain morphology in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). METHODS: Fifty-one patients with MS, 42 patients with NMOSD, and 56 healthy controls (HC) were recruited. The morphological changes in choroid plexus and whole brain tissue were compared between three groups and the correlations between choroid plexus volume and brain atrophy were further investigated. The longitudinal alterations of brain morphology in 25 MS and 20 NMOSD patients were compared. RESULTS: Compared to the HC group, the choroid plexus volumes were increased in the MS group (p < 0.001) but not in the NMOSD group (p > 0.05). Compared to the HC group, the MS group showed reduced cortex thickness, deep gray matter volume, and increased ventricle system volume, and the NMOSD group showed increased third ventricle volume (all p < 0.05, false discovery rate corrected). In the MS group, there were widespread correlations between enlarged choroid plexus volume and reduced cerebral cortex thickness (p < 0.05, r = -0.292~-0.538, false discovery rate corrected). The interval time was not significantly different between the MS (median: 1.37 years) and NMOSD group (median: 1.25 years) (p > 0.05). In MS, compared with the baseline, the right hippocampus and nucleus accumbens volumes were decreased in long follow-up, and bilateral lateral ventricle volumes were increased both in short and long follow-up (all p < 0.05, false discovery rate corrected). CONCLUSIONS: The enlarged choroid plexus related to reduced cortical thickness and progressive local brain atrophy are shown in MS patients, but not obvious in NMOSD patients. KEY POINTS: • MS and NMOSD have different altered patterns in choroid plexus volume and brain atrophy. • The enlarged choroid plexus related to brain atrophy is shown in MS patients, but not obvious in NMOSD patients. • Progressive local brain atrophy is shown in MS patients, but not obvious in NMOSD patients.

Alternative splicing of POUM2 regulates embryonic cuticular formation and tanning in Bombyx mori.

Insect cuticle is an apical extracellular matrix produced by the epidermis, tracheal, hind- and foregut epithelia during embryogenesis and renewed during molting and metamorphosis. However, the underlying regulatory mechanism for embryonic cuticle formation remains largely unclear. Here, we investigate the function of the transcription factor POUM2 in the embryonic cuticular formation in Bombyx mori, a model lepidopteran insect. Clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein-9-mediated knockout of POUM2 resulted in the defect of cuticular deposition, pigmentation, and sclerotization in the embryos. Differentially expressed transcripts analysis of 7-d-old embryos identified 174 up- or downregulated cuticular protein transcripts, 8 upregulated chitin degradation transcripts, 2 downregulated chitin synthesis transcripts and 48 up- or downregulated transcription factor transcripts in the POUM2-/- embryos. The expression levels of the key factors of the tyrosine metabolic pathway, such as tyrosine hydroxylase (Th), Dopa decarboxylase (DDC), and arylalkylamine N-acetyltransferase (aaNAT), were significantly decreased in the POUM2-/- embryos. POUM2 isoform POUM2-L specifically bound the POU cis-regulatory element (CRE) in the Th promoter and increased the transcription of Th, whereas POUM2-S could not bind the POU CRE, although it also increased the transcription of Th. Heterogeneous nuclear ribonucleoprotein Squid-1 directly bound the POUM2 pre-mRNA (messenger RNA) and inhibited the alternative splicing of POUM2-L to POUM2-S mRNA. These results suggest that POUM2 participates in the cuticular formation by regulating the chitin and cuticular protein synthesis and metabolism, and the cuticular pigmentation and sclerotization by regulating tyrosine metabolism during embryogenesis. This study provides new insights into novel function of POUM2 in embryogenesis.

The different damage patterns of short-, middle- and long-range connections between patients with relapse-remitting multiple sclerosis and neuromyelitis optica spectrum disorder.

Objective: To investigate the differences in short-, middle- and long-range connections between patients with relapse-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD), and their correlation with brain tissue volume, structural and functional network parameters. Methods: A total of 51 RRMS, 42 NMOSD and 56 health controls (HC) were recruited. Of these 25 RRMS (median: 1.37 years) and 20 NMOSD (median: 1.25 years) patients were also studied at follow-up. The whole-brain fiber connection was divided into three groups according to the trisected lengths of the tract in HC group, including short-, middle- and long-range connections. The brain tissue features (including total brain tissue and deep grey matter volumes) and parameters of DTI and functional networks (including the shortest path, clustering coefficient, local efficiency and global efficiency) were calculated. The differences in fiber number (FN) and average fractional anisotropy (FA) were compared between RRMS and NMOSD by the One-way ANOVA and post hoc tests. The correlation between the FN or FA and the brain tissue volume, DTI and functional network parameters were further analyzed by Pearson analysis. Results: Compared to HC and NMOSD, the total number of fibers in RRMS was decreased, including the reduced FN of middle- and long-range connections, but increased FN of short-range connections. Compared to HC, the FA of three fibers in RRMS and NMOSD were reduced significantly, and the decrease of FA in RRMS was greater than in NMOSD. There were correlations between the FN of short-, and long-range connections and the atrophy of whole brain tissue in two diseases and structural network topological parameters in RRMS. Additionally, there was no significant difference of FN and FA in short-, middle- and long-range connections between the baseline and follow-up in two diseases. Conclusions: RRMS and NMOSD patients have different patterns of fiber connection damage. The FN of different lengths in RRMS and NMOSD patients may be associated with brain atrophy. The FN and FA of different lengths may explain the decreased efficiency of the structural network in RRMS patients. In the short-term follow-up, neither has worsened damage of different fibers in two diseases.

Estimation of ischemic core in acute ischemic stroke with CT angiography and non-contrast CT: Attenuation changes in ASPECTS regions vs. automated ASPECTS scoring.

Purpose: Reperfusion therapies for acute ischemic stroke due to large-vessel occlusion (AIS-LVO) are highly time-dependent, and large infarction is related to poor outcomes and risk of symptomatic hemorrhage. It is of significance to investigate and optimize the screening means and selection criteria for reperfusion therapies to identify more appropriate patients with better outcomes. This study aimed to compare the performance of attenuation changes vs. automated Alberta Stroke Program Early CT Score (ASPECTS) and using CT angiography (CTA) source images vs. non-contrast CT (NCCT) in distinguishing the infarction extent of ischemic core volumes ≥ 70 ml within different time windows. Methods: A total of 73 patients with AIS-LVO who received multimodal CT were analyzed. The automated software was used to calculate ASPECTS. Attenuation change was defined as the sum of products of relative Hounsfield unit (rHU) values times weighting factors of all 10 ASPECTS regions. rHU value of each region was the HU of the ischemic side over that of the contralateral. The corresponding weighting factors were the regression coefficients derived from a multivariable linear regression model which was used to correlate regional rHU with ischemic core volumes, because each region in the ASPECTS template is weighted disproportionally in the ASPECTS system. Automated ASPECTS and attenuation changes were both calculated using CTA and NCCT, respectively. Results: Attenuation changes were correlated with ischemic core volumes within different time windows (Rho ranging from 0.439 to 0.637). In classification of the ischemic core ≥ 70 ml, the performances of attenuation changes were comparable with ASPECTS (area under the curve [AUC] ranging from 0.799 to 0.891), with DeLong's test (P = 0.079, P = 0.373); using CTA (AUC = 0.842) was not different from NCCT (AUC = 0.838). Conclusion: Attenuation changes in ASPECTS regions were correlated with ischemic core volumes. In the classification of infarction volumes, attenuation changes had a high diagnostic ability comparable with automated ASPECTS. Measurement of attenuation changes is not involved in complicated scoring algorithms. This measurement can be used as an available, rapid, reliable, and accurate means to evaluate infarction extent within different time windows. The usefulness of infarction volumes measured by attenuation changes to identify more appropriate patients for reperfusion therapies can be validated in future clinical trials.

DNA G-quadruplex structure participates in regulation of lipid metabolism through acyl-CoA binding protein.

G-quadruplex structure (G4) is a type of DNA secondary structure that widely exists in the genomes of many organisms. G4s are believed to participate in multiple biological processes. Acyl-CoA binding protein (ACBP), a ubiquitously expressed and highly conserved protein in eukaryotic cells, plays important roles in lipid metabolism by transporting and protecting acyl-CoA esters. Here, we report the functional identification of a G4 in the promoter of the ACBP gene in silkworm and human cancer cells. We found that G4 exists as a conserved element in the promoters of ACBP genes in invertebrates and vertebrates. The BmACBP G4 bound with G4-binding protein LARK regulated BmACBP transcription, which was blocked by the G4 stabilizer pyridostatin (PDS) and G4 antisense oligonucleotides. PDS treatment with fifth instar silkworm larvae decreased the BmACBP expression and triacylglycerides (TAG) level, resulting in reductions in fat body mass, body size and weight and growth and metamorphic rates. PDS treatment and knocking out of the HsACBP G4 in human hepatic adenocarcinoma HepG2 cells inhibited the expression of HsACBP and decreased the TAG level and cell proliferation. Altogether, our findings suggest that G4 of the ACBP genes is involved in regulation of lipid metabolism processes in invertebrates and vertebrates.

DNA methylation-mediated expression of zinc finger protein 615 affects embryonic development in Bombyx mori.

Cell division and differentiation after egg fertilization are critical steps in the development of embryos from single cells to multicellular individuals and are regulated by DNA methylation via its effects on gene expression. However, the mechanisms by which DNA methylation regulates these processes in insects remain unclear. Here, we studied the impacts of DNA methylation on early embryonic development in Bombyx mori. Genome methylation and transcriptome analysis of early embryos showed that DNA methylation events mainly occurred in the 5' region of protein metabolism-related genes. The transcription factor gene zinc finger protein 615 ( ZnF615) was methylated by DNA methyltransferase 1 (Dnmt1) to be up-regulated and bind to protein metabolism-related genes. Dnmt1 RNA interference (RNAi) revealed that DNA methylation mainly regulated the expression of nonmethylated nutrient metabolism-related genes through ZnF615. The same sites in the ZnF615 gene were methylated in ovaries and embryos. Knockout of ZnF615 using CRISPR/Cas9 gene editing decreased the hatching rate and egg number to levels similar to that of Dnmt1 knockout. Analysis of the ZnF615 methylation rate revealed that the DNA methylation pattern in the parent ovary was maintained and doubled in the offspring embryo. Thus, Dnmt1-mediated intragenic DNA methylation of the transcription factor ZnF615 enhances its expression to ensure ovarian and embryonic development.

The Predictive Value of Magnetic Resonance Imaging-based Texture Analysis in Evaluating Histopathological Grades of Breast Phyllodes Tumor.

PURPOSE: Knowing the distinction between benign and borderline/malignant phyllodes tumors (PTs) can help in the surgical treatment course. Herein, we investigated the value of magnetic resonance imaging-based texture analysis (MRI-TA) in differentiating between benign and borderline/malignant PTs. METHODS: Forty-three women with 44 histologically proven PTs underwent breast MRI before surgery and were classified into benign (n = 26) and borderline/malignant groups (n = 18 [15 borderline, 3 malignant]). Clinical and routine MRI parameters (CRMP) and MRI-TA were used to distinguish benign from borderline/malignant PT. In total, 298 texture parameters were extracted from fat-suppression (FS) T2-weighted, FS unenhanced T1-weighted, and FS first-enhanced T1-weighted sequences. To evaluate the diagnostic performance, receiver operating characteristic curve analysis was performed for the K-nearest neighbor classifier trained with significantly different parameters of CRMP, MRI sequence-based TA, and the combination strategy. RESULTS: Compared with benign PTs, borderline/malignant ones presented a higher local recurrence (p = 0.045); larger size (p < 0.001); different time-intensity curve pattern (p = 0.010); and higher frequency of strong lobulation (p = 0.024), septation enhancement (p = 0.048), cystic component (p = 0.023), and irregular cystic wall (p = 0.045). TA of FS T2-weighted images (0.86) showed a significantly higher area under the curve (AUC) than that of FS unenhanced T1-weighted (0.65, p = 0.010) or first-enhanced phase (0.72, p = 0.049) images. The texture parameters of FS T2-weighted sequences tended to have a higher AUC than CRMP (0.79, p = 0.404). Additionally, the combination strategy exhibited a similar AUC (0.89, p = 0.622) in comparison with the texture parameters of FS T2-weighted sequences. CONCLUSION: MRI-TA demonstrated good predictive performance for breast PT pathological grading and could provide surgical planning guidance. Clinical data and routine MRI features were also valuable for grading PTs.

The Application of Diffusion Kurtosis Imaging on the Heterogeneous White Matter in Relapsing-Remitting Multiple Sclerosis.

Objectives: To evaluate the microstructural damage in the heterogeneity of different white matter areas in relapsing-remitting multiple sclerosis (RRMS) patients by using diffusion kurtosis imaging (DKI) and its correlation with clinical and cognitive status. Materials and Methods: Kurtosis fractional anisotropy (KFA), fractional anisotropy (FA), mean kurtosis (MK), and mean diffusivity (MD) in T1-hypointense lesions (T1Ls), pure T2-hyperintense lesions (pure-T2Ls), normal-appearing white matter (NAWM), and white matter in healthy controls (WM in HCs) were measured in 48 RRMS patients and 26 sex- and age-matched HCs. All the participants were assessed with the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Symbol Digit Modalities Test (SDMT) scores as the cognitive status. The Kurtzke Expanded Disability Status Scale (EDSS) scores were used to evaluate the clinical status in RRMS patients. Results: The lowest KFA, FA, and MK values and the highest MD values were found in T1Ls, followed by pure-T2Ls, NAWM, and WM in HCs. The T1Ls and pure-T2Ls were significantly different in FA (p = 0.002) and MK (p = 0.013), while the NAWM and WM in HCs were significantly different in KFA, FA, and MK (p < 0.001; p < 0.001; p = 0.001). The KFA, FA, MK, and MD values in NAWM (r = 0.360, p = 0.014; r = 0.415, p = 0.004; r = 0.369, p = 0.012; r = -0.531, p < 0.001) were correlated with the MMSE scores and the FA, MK, and MD values in NAWM (r = 0.423, p = 0.003; r = 0.427, p = 0.003; r = -0.359, p = 0.014) were correlated with the SDMT scores. Conclusion: Applying DKI to the imaging-based white matter classification has the potential to reflect the white matter damage and is correlated with cognitive impairment.

Knock down of target genes by RNA interference in the embryos of lepidopteran insect, Bombyx mori.

RNA interference (RNAi) is a technique used for posttranscriptional gene silencing, but lepidopteran insects are not sensitive to RNAi. Here, we present a protocol for knocking down the expression level of target genes by RNAi in Bombyx mori embryos. We describe the preparation of double-stranded RNAs (dsRNAs) of target genes, followed by microinjection of embryos at different developmental stages, with single or mixed dsRNA. Finally, we use RT-qPCR to verify RNAi efficiency. For complete details on the use and execution of this protocol, please refer to Xu et al. (2021).

Large-scale screening of i-motif binding compounds in the silkworm, Bombyx mori.

DNA secondary structure i-motif involves in gene transcription and considered as a novel target for cancer gene therapy. I-motif-binding compounds can either stabilize or destroy the structure, resulting in change in target gene transcription. In this study, a large-scale screening of binding compounds was conducted using the i-motif structure of BmPOUM2, a transcription factor in silkworm, Bombyx mori. Surface plasmon resonance imaging (SPRi) high-throughput binding screening of 3642 compounds found 60 compounds with an binding affinity Kd of 10-7-10-6 M. SPRi and circular dichroism (CD) double screening demonstrated that the BmPOUM2 i-motif structure bound the compounds IF1, IF3, IF4, IF6 and IF7 with Kd of 10-7 M, and the compounds IF2 and tetrakis (4-N-methylpyridyl) porphine (TMPyP4) with a Kd of 10-8 M. Interestingly, IF2, IF3, IF4, IF6 and IF7 promoted the binding of the i-motif-binding protein BmILF with the i-motif structure, whereas TMPyP4 inhibited the binding. This study provided a list of compounds that have potential applications in functional analysis of i-motif structure and in pesticide and drug development through gene transcription regulation by i-motif structure.

Quantitative Susceptibility Mapping-Derived Radiomic Features in Discriminating Multiple Sclerosis From Neuromyelitis Optica Spectrum Disorder.

Objectives: To implement a machine learning model using radiomic features extracted from quantitative susceptibility mapping (QSM) in discriminating multiple sclerosis (MS) from neuromyelitis optica spectrum disorder (NMOSD). Materials and Methods: Forty-seven patients with MS (mean age = 40.00 ± 13.72 years) and 36 patients with NMOSD (mean age = 42.14 ± 12.34 years) who underwent enhanced gradient-echo T2*-weighted angiography (ESWAN) sequence in 3.0-T MRI were included between April 2017 and October 2019. QSM images were reconstructed from ESWAN, and QSM-derived radiomic features were obtained from seven regions of interest (ROIs), including bilateral putamen, globus pallidus, head of the caudate nucleus, thalamus, substantia nigra, red nucleus, and dentate nucleus. A machine learning model (logistic regression) was applied to classify MS and NMOSD, which combined radiomic signatures and demographic information to assess the classification accuracy using the area under the receiver operating characteristic (ROC) curve (AUC). Results: The radiomics-only models showed better discrimination performance in almost all deep gray matter (DGM) regions than the demographic information-only model, with the highest AUC in DN of 0.902 (95% CI: 0.840-0.955). Moreover, the hybrid model combining radiomic signatures and demographic information showed the highest discrimination performance which achieved the AUC of 0.927 (95% CI: 0.871-0.984) with fivefold cross-validation. Conclusion: The hybrid model based on QSM and powered with machine learning has the potential to discriminate MS from NMOSD.

MRI characteristics of brain edema in preeclampsia/eclampsia patients with posterior reversible encephalopathy syndrome.

BACKGROUND: The neuroimaging manifestations of eclampsia and preeclampsia often overlap, mainly presenting as posterior reversible encephalopathy syndrome (PRES). The purpose of this retrospective study was to compare the extent and nature of brain edema in eclampsia and preeclampsia patients with PRES based on MRI characteristics. METHODS: One hundred fifty women diagnosed with preeclampsia-eclampsia and undergoing cranial MRI were enrolled; 24 of these were diagnosed as having eclampsia. According to clinicoradiologic diagnosis of PRES, eligible patients were classified as having eclampsia with PRES (group E-PRES) and preeclampsia with PRES (group P-PRES). A scale on T2W FLAIR-SPIR images was established to evaluate the extent of brain edema, and the score of brain edema (SBE) of both groups was compared. In patients of the two groups who also underwent DWI sequence, the presence or absence of hyperintensity on DWI and hypointensity on ADC maps were determined to compare the nature of brain edema. Furthermore, clinical and biochemical data of the two groups were compared. RESULTS: The incidence of PRES in eclampsia patients was significantly higher than that in preeclampsia patients (87.50% vs. 46.03%, P<0.001). The SBE of all regions and typical regions in group E-PRES patients were significantly higher than those in group P-PRES patients (15.88±8.72 vs. 10.90±10.21, P=0.021; 8.52±3.87 vs. 5.01±4.19, P=0.002; respectively). The presence of hyperintensity on DWI was determined more frequently in group E-PRES patients than group P-PRES patients (71.43% vs. 32.00%, P=0.024). Age, systolic blood pressure, white blood cell count, neutrophil count and percentage of neutrophils were significantly different between the two groups (P<0.05). CONCLUSIONS: Certain MRI characteristics that reflect the extent and nature of brain edema were different between eclampsia and preeclampsia patients with PRES. Additional prospective studies are still required to explore whether these MRI characteristics of brain edema may further become a potential predictor for eclamptic seizures in preeclampsia patients with PRES.