Assessment of chemotherapy resistance changes in human colorectal cancer xenografts in rats based on MRI histogram features.

Purpose: We investigated the value of magnetic resonance imaging (MRI) histogram features, a non-invasive method, in assessing the changes in chemoresistance of colorectal cancer xenografts in rats. Methods: A total of 50 tumor-bearing mice with colorectal cancer were randomly divided into two groups: control group and 5-fluorouracil (5-FU) group. The MRI histogram characteristics and the expression levels of p53 protein and MRP1 were obtained at 24 h, 48 h, 72 h, 120 h, and 168 h after treatment. Results: Sixty highly repeatable MRI histogram features were obtained. There were 16 MRI histogram parameters and MRP1 resistance protein differences between groups. At 24 h after treatment, the MRI histogram texture parameters of T2-weighted imaging (T2WI) images (10%, 90%, median, energy, and RootMeanSquared) and D images (10% and Range) were positively correlated with MRP1 (r = 0.925, p = 0.005). At 48 h after treatment, histogram texture parameters of apparent diffusion coefficient (ADC) images (Energy) were positively correlated with the presence of MRP1 resistance protein (r = 0.900, p = 0.037). There was no statistically significant difference between MRI histogram features and p53 protein expression level. Conclusions: MRI histogram texture parameters based on T2WI, D, and ADC maps can help to predict the change of 5-FU resistance in colorectal cancer in the early stage and provide important reference significance for clinical treatment.

Purine and carbohydrate availability drive Enterococcus faecalis fitness during wound and urinary tract infections.

IMPORTANCE: Although E. faecalis is a common wound pathogen, its pathogenic mechanisms during wound infection are unexplored. Here, combining a mouse wound infection model with in vivo transposon and RNA sequencing approaches, we identified the E. faecalis purine biosynthetic pathway and galactose/mannose MptABCD phosphotransferase system as essential for E. faecalis acute replication and persistence during wound infection, respectively. The essentiality of purine biosynthesis and the MptABCD PTS is driven by the consumption of purine metabolites by E. faecalis during acute replication and changing carbohydrate availability during the course of wound infection. Overall, our findings reveal the importance of the wound microenvironment in E. faecalis wound pathogenesis and how these metabolic pathways can be targeted to better control wound infections.

Resting-State Functional Magnetic Resonance Imaging as an Indicator of Neuropsychological Changes in Type 1 Narcolepsy.

RATIONALE AND OBJECTIVES: To explore indicators of neuropsychological changes in patients with type 1 narcolepsy (NT1) using resting-state functional magnetic resonance imaging (rs-fMRI). MATERIALS AND METHODS: Thirty-four NT1 patients and 34 age- and sex-matched healthy volunteers were recruited for neuropsychiatric assessments and rs-fMRI data acquisition. Fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and related brain functional connectivity (FC) were calculated for the two groups and compared using a two-sample t test with cluster-level FDR correction. Moreover, partial correlation analysis was performed between these functional values of changed brain regions and clinical scales. RESULTS: Compared to those of healthy controls, spontaneous functional activities were significantly weakened in patients with NT1 in regions such as the left/right posterior cerebellum lobe, left inferior temporal gyrus, and left dorsolateral superior frontal gyrus, whereas those in regions such as the left middle occipital gyrus, right inferior occipital gyrus, and left/right lingual gyrus were significantly strengthened. Furthermore, NT1 patients displayed significantly changed FCs between the left/right anterior cingulate gyrus (ACG) and regions such as the left/right cerebellum, left middle occipital gyrus, and left inferior frontal gyrus in the operculum. In partial correlation analysis, the functions in the left dorsolateral superior frontal gyrus were significantly related to the Trail Making Tests (TMT) score. Moreover, the FC between the left ACG and left inferior frontal gyrus in the operculum was highly correlated with anxiety and depression features, including the Hamilton Anxiety Scale (HAMA) score and Hamilton Depression Rating Scale (HAMD-17) score. CONCLUSION: Patients with NT1 exhibited abnormalities in the anterior cingulate cortex, frontal-parietal cortex, hippocampus, and left/right posterior cerebellum lobe. The deactivation of the left frontal-temporal cortex is stronger, which is involved in the cognitive decline and mental disorders in these patients. Damage to the ACG may affect its FC with other regions and cause cognition and emotion dysregulation, perhaps by impairing patients' visual pathways and frontal-temporal-parietal networks. Hence, these could be important biomarkers for their neuropsychological changes.

Kinesin-14 KIFC1 promotes acrosome formation and chromatin maturation during mouse spermiogenesis.

KIFC1, a member of kinesin-14 subfamily motors, is essential for meiotic cell division and acrosome formation during spermatogenesis. However, the functions of KIFC1 in the formation and maintenance of the acrosome in male germ cells remain to be elucidated. In this study, we report the structural deformities of acrosomes in the in vivo KIFC1 inhibition mouse models. The proacrosomal vesicles diffuse into the cytoplasm and form atypical acrosomal granules. This phenotype is consistent with globozoospermia patients and probably results from the failure of the Golgi-derived vesicle trafficking and actin filament organization. Moreover, the multinucleated and undifferentiated spermatogenic cells in the epidydimal lumen after KIFC1 inhibition reveal the specific roles of KIFC1 in regulating post-meiotic maturation. Overall, our results uncover KIFC1 as an essential regulator in the trafficking, fusion and maturation of acrosomal vesicles during spermiogenesis.

Auranofin inhibits virulence pathways in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is widely attributed as the leading cause of hospital-acquired infections. Due to intrinsic antibiotic resistance mechanisms and the ability to form biofilms, P. aeruginosa infections are challenging to treat. P. aeruginosa employs multiple virulence mechanisms to establish infections, many of which are controlled by the global virulence regulator Vfr. An attractive strategy to combat P. aeruginosa infections is thus the use of anti-virulence compounds. Here, we report the discovery that FDA-approved drug auranofin attenuates virulence pathways in P. aeruginosa, including quorum sensing (QS) and Type IV pili (TFP). We show that auranofin acts via multiple targets, one of which being Vfr. Consistent with inhibition of QS and TFP expression, we show that auranofin attenuates biofilm maturation, and when used in combination with colistin, displays strong synergy in eradicating P. aeruginosa biofilms. Auranofin may have immediate applications as an anti-virulence drug against P. aeruginosa infections.

A CT-Based Radiomics Nomogram Combined with Clinic-Radiological Characteristics for Preoperative Prediction of the Novel IASLC Grading of Invasive Pulmonary Adenocarcinoma.

RATIONALE AND OBJECTIVES: The novel International Association for the Study of Lung Cancer (IASLC) grading system of invasive lung adenocarcinoma (ADC) demonstrated a remarkable prognostic effect and enabled numerous patients to benefit from adjuvant chemotherapy. We sought to build a CT-based nomogram for preoperative prediction of the IASLC grading. MATERIALS AND METHODS: This work retrospectively analyzed the CT images and clinical data of 303 patients with pathologically confirmed invasive ADC. The histological subtypes and radiological characteristics of the patients were re-evaluated. Radiomics features were extracted, and the optimal subset of features was established by ANOVA, spearman correlation analysis, and the least absolute shrinkage and selection operator (LASSO). Univariate and multivariate analyses identified the independent clinical and radiological variables. Finally, multivariate logistic regression analysis incorporated clinical, radiological, and optimal radiomics features into the nomogram. Receiver operating characteristic (ROC) curve, and accuracy were applied to assess the model's performance. Decision curve analysis (DCA), and calibration curve were applied to assess the clinical usefulness. RESULTS: Nine selected CT image features were used to develop the radiomics model. The accuracy, precision, sensitivity, and specificity of the radiomics model outperformed the clinic-radiological model in the training and testing sets. Integrating Radscore with independent radiological characteristics showed higher prediction performance than clinic-radiological characteristics alone in the training (AUC, 0.915 vs. 0.882; DeLong, p < 0.05) and testing (AUC, 0.838 vs. 0.782; DeLong, p < 0.05) sets. Good calibration and decision curve analysis demonstrated the clinical usefulness of the nomogram. CONCLUSION: Radiomics features effectively predict high-grade ADC. The combined nomogram may facilitate selecting patients who benefit from adjuvant treatment.

Structurally diverse polycyclic polyprenylated acylphloroglucinols with protective effect on human vein endothelial cells injured by high-glucose from Hypericum acmosepalum N. Robson.

Hyperacmotone A, a polycyclic polyprenylated acylphloroglucinol (PPAP) with an unprecedented skeleton, along with five undescribed congeners and eleven reported ones, was isolated from Hypericum acmosepalum. Hyperacmotone A possesses a unique monocyclic ring skeleton based on a cyclopent-4-ene-1,3-dione acylphloroglucinol core. Their structures were elucidated by extensive analysis of HRESIMS, NMR, biogenetic pathway, and quantum-chemical calculations. In addition, hypercohone G exhibited significant protective effects on high-glucose-injured HUVECs.

Hepatotoxicity and the role of the gut-liver axis in dogs after oral administration of zinc oxide nanoparticles.

Zinc oxide nanoparticles (ZnO NPs) have been used in many fields, and people are concerned about its effects on health. The present study reported the changes in liver metabolites and intestinal microbiota induced by overused ZnO NPs in dogs and explored the related mechanisms of liver injury induced by ZnO NPs. The results showed that overused ZnO NPs promote zinc accumulation in the liver and increase liver coefficient and serum liver-related indexes. In addition, the overuse of ZnO NPs increase the reactive oxygen species levels, affecting the hepatocyte antioxidant capacity and mitochondrial function. Results showed that ZnO NPs significantly inhibited the hepatocyte apoptosis via the Cytc pathway and promoted the autophagy via activating the mTOR/ATG5 pathway. Metabolic analysis of liver tissue showed that 81 metabolites changed overall and mainly affected the glycerophospholipid metabolism. ZnO NPs can significantly change the richness and diversity of the intestinal bacteria in dogs, increasing the abundance of Firmicutes and Actinobacteria while reducing the bacterial abundance of Proteobacteria. In conclusion, the results suggest that overexposure to ZnO NPs can lead to the disruption of intestinal microbiome and liver metabolites in dogs, which ultimately leads to liver damage.

Measuring the effects of mind wandering in people with insomnia: A driving simulator study.

Purpose: Studies have shown that individuals with insomnia experience more frequent and longer episodes of mind wandering (MW) while driving. However, the effect of the interaction between insomnia and MW on driving behavior is not fully understood. This study aimed to gain deeper insights into the relationships among insomnia, MW, and driving behavior. Patients and methods: Forty-two participants (21 diagnosed with insomnia and 21 controls) were recruited, and subjective sleep quality and cognitive function were assessed. A driving simulator experiment with a within-subject design was performed, involving two distraction tasks (no-distraction task versus MW task) and two driving scenarios (lane-keeping versus lane-changing). Results: In the lane-keeping scenario, there was no significant between-group difference (people with insomnia and controls) in longitudinal driving performance for the no-distraction task, although the interaction between MW and insomnia significantly increased drivers' longitudinal control variation. Correlation analysis confirmed that longitudinal driving performance was positively correlated with sleep quality and the cognitive level. Unlike longitudinal driving performance, lateral driving performance was significantly weaker in people with insomnia than in controls under both distraction tasks. In the lane-changing scenario, although there was no between-group difference in driving performance, the MW task led to significant changes in driving performance within each group compared with the no-distraction task, and these findings were associated with cognitive function, but not with sleep quality. Conclusion: These findings show that insomnia and MW combined can lead to reduced driving performance. Further research is needed to elucidate the factors that influence this phenomenon.

Value of IVIM in Differential Diagnoses between Benign and Malignant Solitary Lung Nodules and Masses: A Meta-analysis.

Purpose: This study aims to evaluate the accuracy of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in distinguishing malignant and benign solitary pulmonary nodules and masses. Methods: Studies investigating the diagnostic accuracy of IVIM-DWI in lung lesions published through December 2020 were searched. The standardized mean differences (SMDs) of the apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudo-diffusivity (D*), and perfusion fraction (f) were calculated. The sensitivity, specificity, area under the curve (AUC), publication bias, and heterogeneity were then summarized, and the source of heterogeneity and the reliability of combined results were explored by meta-regression and sensitivity analysis. Results: A total of 16 studies including 714 malignant and 355 benign lesions were included. Significantly lower ADC, D, and f values were found in malignant pulmonary lesions compared to those in benign lesions. The D value showed the best diagnostic performance (sensitivity = 0.90, specificity = 0.71, AUC = 0.91), followed by ADC (sensitivity = 0.84, specificity = 0.75, AUC = 0.88), f (sensitivity = 0.70, specificity = 0.62, AUC = 0.71), and D * (sensitivity = 0.67, specificity = 0.61, AUC = 0.67). There was an inconspicuous publication bias in ADC, D, D* and f values, moderate heterogeneity in ADC, and high heterogeneity in D, D*, and f values. Subgroup analysis suggested that both ADC and D values had a significant higher sensitivity in "nodules or masses" than that in "nodules." Conclusions: The parameters derived from IVIM-DWI, especially the D value, could further improve the differential diagnosis between malignant and benign solitary pulmonary nodules and masses.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier: CRD42021226664.

Enterococcus faecalis Antagonizes Pseudomonas aeruginosa Growth in Mixed-Species Interactions.

Enterococcus faecalis is often coisolated with Pseudomonas aeruginosa in polymicrobial biofilm-associated infections of wounds and the urinary tract. As a defense strategy, the host innately restricts iron availability at infection sites. Despite their coprevalence, the polymicrobial interactions of these two species in biofilms and under iron-restricted conditions remain unexplored. Here, we show that E. faecalis inhibits P. aeruginosa growth within biofilms when iron is restricted. E. faecalis lactate dehydrogenase (ldh1) gives rise to l-lactate production during fermentative growth. We find that an E. faecalis ldh1 mutant fails to inhibit P. aeruginosa growth. Additionally, we demonstrate that ldh1 expression is induced under iron-restricted conditions, resulting in increased lactic acid exported and, consequently, a reduction in local environmental pH. Together, our results suggest that E. faecalis synergistically inhibits P. aeruginosa growth by decreasing environmental pH and l-lactate-mediated iron chelation. Overall, this study emphasizes the importance of the microenvironment in polymicrobial interactions and how manipulating the microenvironment can impact the growth trajectory of bacterial communities. IMPORTANCE Many infections are polymicrobial and biofilm-associated in nature. Iron is essential for many metabolic processes and plays an important role in controlling infections, where the host restricts iron as a defense mechanism against invading pathogens. However, polymicrobial interactions between pathogens are underexplored under iron-restricted conditions. Here, we explore the polymicrobial interactions between commonly coisolated E. faecalis and P. aeruginosa within biofilms. We find that E. faecalis modulates the microenvironment by exporting lactic acid which further chelates already limited iron and also lowers the environmental pH to antagonize P. aeruginosa growth under iron-restricted conditions. Our findings provide insights into polymicrobial interactions between bacteria and how manipulating the microenvironment can be taken advantage of to better control infections.

A transcriptomic analysis based on aberrant methylation levels revealed potential novel therapeutic targets for nasopharyngeal carcinoma.

Background: This study aimed to identify potential novel therapeutic targets for nasopharyngeal carcinoma (NPC) by identifying aberrantly methylated-differentially expressed genes (DEGs) and pathways based on a comprehensive bioinformatics analysis. Methods: Eight gene expression data sets and 2 methylation microarray data sets that included NPC and control groups from the Gene Expression Omnibus were identified. Meta-analyses of the DEGs were performed using the online analysis database "NetworkAnalyst". Aberrantly methylated gene loci were obtained from the GEO2R. Aberrantly methylated DEGs were obtained from Venn diagrams. The enrichment analysis was carried out on the "Metascape" website, and the protein-protein interaction (PPI) network construction, network analysis, and visualization of the analysis results were carried out on the "String" website using "Cytoscape" software. Results: In total, 544 hypomethylation high-expression genes and 164 hypermethylation low-expression genes were obtained. The enrichment and PPI network analyses suggested that several pathways and hub genes with abnormal gene expression accompanied by methylation change, including inositol-trisphosphate 3-kinase B (ITPKB), G protein subunit beta 5 (GNB5), FYN proto-oncogene, Src family tyrosine kinase (FYN), LCK proto-oncogene, Src family tyrosine kinase (LCK), nuclear factor of activated T cells 1 (NFATC1), GNAS complex locus (GNAS), protein kinase C beta (PRKCB), zeta chain of T cell receptor associated protein kinase 70 (ZAP70), lysophosphatidic acid receptor 1 (LPAR1), protein kinase C epsilon (PRKCE), tumor protein p53 (TP53), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fibronectin 1 (FN1), cyclin D1 (CCND1), vascular endothelial growth factor A (VEGFA), HRas proto-oncogene, GTPase (HRAS), signal transducer and activator of transcription 3 (STAT3), fibroblast growth factor 2 (FGF2), amyloid beta precursor protein (APP), and matrix metallopeptidase 2 (MMP2), may be related to the occurrence of nasopharyngeal carcinoma . Conclusions: The identification of novel and important pathways and hub genes and their roles in the occurrence and development of NPC will guide clinical research and the development of pharmaceutical targets.

Design and application of unplanned extubation quality index management system based on direct data acquisition / 中国实用护理杂志

Objective:To acquire more scientific, accurate and efficient unplanned extubation (UEX) quality management data by using information technology to directly take the quality index data of unplanned extubation from the nursing medical record system.Methods:From June 2019 to August 2019, a knowledge base of pipeline management including the name of pipeline, pipeline evaluation, pipeline care measures, and reasons for unplanned extubation of pipeline was established in Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine. Through the analysis of each node of pipeline management, pipeline management system was established. And the non-planned pipeline management data set was directly collected to the nursing quality management system for statistics and analysis, which was verified.Results:In clinical application from September 2019 to september 2020, the direct collection of unplanned extubation quality index data saved 496 hours of nursing labor costs per month, and the accuracy of direct data collection increased from 95.8% (161/168) in trial operation to 100.0% (494/494). The underreporting rate of adverse events decreased to 0. Satisfaction with the application of the quality index management system for unplanned extubation was (4.35 ± 0.73) points.Conclusions:The direct collection of quality index data for unplanned extubation improves the accuracy of the data. Nurses no longer need to report unplanned extubation incidents. The clinical nursing information system and the nursing management system are interconnected to improve the management efficiency of unplanned extubation. It is worthy of application and promotion in clinic.

Pre-operative Prediction of Ki-67 Expression in Various Histological Subtypes of Lung Adenocarcinoma Based on CT Radiomic Features.

Purpose: The aims of this study were to combine CT images with Ki-67 expression to distinguish various subtypes of lung adenocarcinoma and to pre-operatively predict the Ki-67 expression level based on CT radiomic features. Methods: Data from 215 patients with 237 pathologically proven lung adenocarcinoma lesions who underwent CT and immunohistochemical Ki-67 from January 2019 to April 2021 were retrospectively analyzed. The receiver operating curve (ROC) identified the Ki-67 cut-off value for differentiating subtypes of lung adenocarcinoma. A chi-square test or t-test analyzed the differences in the CT images between the negative expression group (n = 132) and the positive expression group (n = 105), and then the risk factors affecting the expression level of Ki-67 were evaluated. Patients were randomly divided into a training dataset (n = 165) and a validation dataset (n = 72) in a ratio of 7:3. A total of 1,316 quantitative radiomic features were extracted from the Analysis Kinetics (A.K.) software. Radiomic feature selection and radiomic classifier were generated through a least absolute shrinkage and selection operator (LASSO) regression and logistic regression analysis model. The predictive capacity of the radiomic classifiers for the Ki-67 levels was investigated through the ROC curves in the training and testing groups. Results: The cut-off value of the Ki-67 to distinguish subtypes of lung adenocarcinoma was 5%. A comparison of clinical data and imaging features between the two groups showed that histopathological subtypes and air bronchograms could be used as risk factors to evaluate the expression of Ki-67 in lung adenocarcinoma (p = 0.005, p = 0.045, respectively). Through radiomic feature selection, eight top-class features constructed the radiomic model to pre-operatively predict the expression of Ki-67, and the area under the ROC curves of the training group and the testing group were 0.871 and 0.8, respectively. Conclusion: Ki-67 expression level with a cut-off value of 5% could be used to differentiate non-invasive lung adenocarcinomas from invasive lung adenocarcinomas. It is feasible and reliable to pre-operatively predict the expression level of Ki-67 in lung adenocarcinomas based on CT radiomic features, as a non-invasive biomarker to predict the degree of malignant invasion of lung adenocarcinoma, and to evaluate the prognosis of the tumor.

Evaluation of axial length/total corneal refractive power ratio as a potential marker for ocular diagnosis of Marfan's syndrome in children.

AIM: To investigate whether the axial length (AL)/total corneal refractive power (TCRP) ratio is a sensitive and simple factor that can be used for the early diagnosis of Marfan's syndrome (MFS) in children. METHODS: The relationship between the AL/TCRP ratio and the diagnosis of MFS for 192 eyes in 97 children were evaluate. The biological characteristics, including age, sex, AL, and TCRP, were collected from medical records. Receiver operating characteristic (ROC) curve analysis was performed to investigate whether the AL/TCRP ratio effectively distinguishes MFS from other subjects. The Youden index was used to re-divide the whole population into two groups according to an AL/TCRP ratio of 0.59. RESULTS: Of 96 subjects (mean age 7.46±3.28y) evaluated, 56 (110 eyes) had a definite diagnosis of MFS in childhood based on the revised Ghent criteria, 41 (82 eyes) with diagnosis of congenital ectopia lentis (EL) were included as a control group. AL was negatively correlated with TCRP, with a linear regression coefficient of -0.36 (R 2=0.08). A significant correlation was found between age and the AL/TCRP ratio (P=0.023). ROC curve analysis showed that the AL/TCRP ratio distinguished MFS from the other patients at a threshold of 0.59. MFS patients were present in 24/58 (41.38%) patients with an AL/TCRP ratio of ≤0.59 and in 34/39 (87.18%) patients with an AL/TCRP ratio of >0.59. CONCLUSION: An AL/TCRP ratio of >0.59 is significantly associated with the risk of MFS. The AL/TCRP ratio should be measured as a promising marker for the prognosis of children MFS. Changes in the AL/TCRP ratio should be monitored over time.

Acmoxanthones A-E, New Lavandulated Xanthones from Hypericum acmosepalum N. Robson.

Acmoxanthones A-E (1-5), five new lavandulylated xanthones, were isolated from the aerial parts of Hypericum acmosepalum, together with four known xanthones. Their structures with absolute configurations were elucidated on the basis of analysis of MS, NMR and chiroptical properties. A bioassay against high glucose-induced damage on human umbilical vein endothelial cells (HUVECs) showed ananixanthone (6) and osajaxanthone (7) had potential antioxidative damage activity with EC50 values of 10.5 µg/mL and 7.6 µg/mL, respectively, while 3-hydroxy-2,4-dimethoxyxanthone (8) exhibited cytotoxic effect on the damaged cells with IC50 values of 7.1 µg/mL.

Structurally diverse polyprenylated acylphloroglucinols from Hypericum uralum Buch.-Ham. ex D. Don.

Uralins A - D, four undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) featuring an unprecedented fused hexacyclic architecture, a unique monocyclic tetra-seco-tetranor-b-PPAP, an oxidative b-PPAP and a rare norspiroindane-type m-PPAP, respectively, were isolated from the aerial parts of Hypericum uralum, along with ten known PPAPs. Their structures and absolute configurations were elucidated by extensive spectroscopic techniques (MS, NMR, [α]D, CD), conceivable biogenetic pathways and time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations. Biological assays showed three b-PPAPs had moderate antioxidative damage activities, while spiroindanes exhibited moderate cytotoxic effects.

Down-regulation of SORL1 is associated with Alzheimer's disease through activating ABC transporter pathway.

Alzheimer's disease (AD) is a common neurodegenerative disease with high morbidity among elderly people. A genetic attribution has been extensively proved. Here, we propose to further prioritize genes that harbor single nucleotide variation (SNV) or structural variation (SV) for AD and explore the underlying potential mechanisms through exploiting their expression and methylation spectra. A high-confidence AD-associated candidate gene list was obtained from the ClinVar and Human Gene Mutation Database (HGMD). Genome-wide methylation and expression profiles of AD and normal subjects were downloaded from the Gene Expression Omnibus (GEO). Through comprehensive comparison of expression and methylation levels between AD and normal samples, as well as different stages of AD samples, SORL1 was identified as the most plausible gene for AD incidence and progression. Gene Set Enrichment Analysis (GSEA) revealed significant activation of the ABC (ATP binding cassette) transporter with the aberrant up-regulation of SORL1 within AD samples. This study unfolds the expression and methylation spectra of previously probed genes with SNV or SV in AD for the first time, and reports an aberrant activation of the ABC transporter pathway that might contribute to AD progression. This should shed some light on AD diagnosis and precision treatment.

The value of multiparametric histogram features based on intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the differential diagnosis of liver lesions.

BACKGROUND: The present study analyzed whole-lesion histogram parameters from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) to explore the clinical value of IVIM histogram features in the differentiation of liver lesions. METHODS: In this retrospective study, 33 cases of hepatic hemangioma (HH), 22 cases of hepatic cysts (HC), and 34 cases of hepatocellular carcinoma (HCC) were underwent IVIM-DWI (b =0-600 s/mm2), which were confirmed pathologically and clinically. The data were processed by IVIM model to obtain the following quantitative indicators: perfusion fraction (f), slow diffusion coefficient (D), and pseudo-diffusion coefficient (or fast diffusion coefficient, D*). The region of interest in the largest solid part of the lesion was delineated for histogram analysis of the correlation between tissue image and lesion type. The relevant histogram parameters were obtained and statistically analyzed. The characteristic histogram parameters for HH, HC, and HCC were compared to find significantly different parameters. The diagnostic efficacies of these parameters for HH, liver cysts, and HCC were assessed using the receiver operating characteristic (ROC) curves. RESULTS: There were significant differences in the maximum diameter, maximum value, minimum value, mean, median, standard deviation, uniformity, skewness, kurtosis, volume, 10th percentile (P10) of D, and 90th percentile (P90) of D between the three groups (P<0.05). The maximum diameter, minimum value, entropy, and volume of D* differed significantly between the three groups (P<0.05). The maximum diameter, minimum value, mean, median, skewness, kurtosis, volume, P10, and P90 of f differed significantly between the three groups (P<0.05). The largest area under the ROC curve (AUC) for both D* and f was that of volume (AUC =0.883 for both). When 1438.802 was used as the volume cut-off, the sensitivity and specificity of volume in differentiating between HH and HC were 87.88 and 77.27, respectively, and the sensitivity and specificity of volume in differentiating between HC and HCC were 77.27 and 85.29. CONCLUSIONS: A multiparametric histogram from IVIM-DWI magnetic resonance imaging (MRI) is an effective means of identifying HH, HC, and HCC that provides valuable reference information for clinical diagnosis.

Overcoming the challenge of establishing biofilms in vivo: a roadmap for Enterococci.

Enterococcus faecalis forms single and mixed-species biofilms on both tissue and medical devices in the host, often under exposure to fluid flow, giving rise to infections that are recalcitrant to treatment. The factors that drive enterococcal biofilm formation in the host, however, remain unclear. Recent reports in other pathogens show how surface sensing by bacteria can trigger the transition from planktonic to sessile lifestyle. Fluid flow can enhance initial adhesion, but also influence quorum sensing. Biofilm-specific factors, as well as biofilm size and extracellular polymeric substances, can compromise opsonization and phagocytosis. Bacterial interspecies synergy can create favorable conditions in the host for biofilm formation. Through these concepts, we define the knowledge gaps in understanding host-associated E. faecalis biofilm formation and propose a roadmap for future investigations.