Molecular basis for control of antibiotic production by a bacterial hormone.

Actinobacteria produce numerous antibiotics and other specialized metabolites that have important applications in medicine and agriculture1. Diffusible hormones frequently control the production of such metabolites by binding TetR family transcriptional repressors (TFTRs), but the molecular basis for this remains unclear2. The production of methylenomycin antibiotics in Streptomyces coelicolor A3(2) is initiated by the binding of 2-alkyl-4-hydroxymethylfuran-3-carboxylic acid (AHFCA) hormones to the TFTR MmfR3. Here we report the X-ray crystal structure of an MmfR-AHFCA complex, establishing the structural basis for hormone recognition. We also elucidate the mechanism for DNA release upon hormone binding through the single-particle cryo-electron microscopy structure of an MmfR-operator complex. DNA binding and release assays with MmfR mutants and synthetic AHFCA analogues define the role of individual amino acid residues and hormone functional groups in ligand recognition and DNA release. These findings will facilitate the exploitation of actinobacterial hormones and their associated TFTRs in synthetic biology and in the discovery of new antibiotics.

Developmental programming and lineage branching of early human telencephalon.

The dorsal and ventral human telencephalons contain different neuronal subtypes, including glutamatergic, GABAergic, and cholinergic neurons, and how these neurons are generated during early development is not well understood. Using scRNA-seq and stringent validations, we reveal here a developmental roadmap for human telencephalic neurons. Both dorsal and ventral telencephalic radial glial cells (RGs) differentiate into neurons via dividing intermediate progenitor cells (IPCs_div) and early postmitotic neuroblasts (eNBs). The transcription factor ASCL1 plays a key role in promoting fate transition from RGs to IPCs_div in both regions. RGs from the regionalized neuroectoderm show heterogeneity, with restricted glutamatergic, GABAergic, and cholinergic differentiation potencies. During neurogenesis, IPCs_div gradually exit the cell cycle and branch into sister eNBs to generate distinct neuronal subtypes. Our findings highlight a general RGs-IPCs_div-eNBs developmental scheme for human telencephalic progenitors and support that the major neuronal fates of human telencephalon are predetermined during dorsoventral regionalization with neuronal diversity being further shaped during neurogenesis and neural circuit integration.

The FSH-mTOR-CNP signaling axis initiates follicular antrum formation by regulating tight junction, ion pumps, and aquaporins.

The initial formation of the follicular antrum (iFFA) serves as a dividing line between gonadotropin-independent and gonadotropin-dependent folliculogenesis, enabling the follicle to sensitively respond to gonadotropins for its further development. However, the mechanism underlying iFFA remains elusive. Herein, we reported that iFFA is characterized by enhanced fluid absorption, energy consumption, secretion, and proliferation and shares a regulatory mechanism with blastula cavity formation. By use of bioinformatics analysis, follicular culture, RNA interference, and other techniques, we further demonstrated that the tight junction, ion pumps, and aquaporins are essential for follicular fluid accumulation during iFFA, as a deficiency of any one of these negatively impacts fluid accumulation and antrum formation. The intraovarian mammalian target of rapamycin-C-type natriuretic peptide pathway, activated by follicle-stimulating hormone, initiated iFFA by activating tight junction, ion pumps, and aquaporins. Building on this, we promoted iFFA by transiently activating mammalian target of rapamycin in cultured follicles and significantly increased oocyte yield. These findings represent a significant advancement in iFFA research, further enhancing our understanding of folliculogenesis in mammals.

Analytical characterization of full, intermediate, and empty AAV capsids.

Manufacturing of recombinant adeno-associated virus (AAV) vectors produces three types of capsids: full, intermediate, and empty. While there are different opinions about the impact of intermediate and empty capsids on safety and efficacy of AAV products, they are generally considered impurities because they are not the intended fully intact vector product. The presence of these impurities could impact product efficacy due to potential competition with fully packaged AAVs for cellular transduction, as well as have potential implications to patient safety due to increased capsid load during dosing. To determine the impact of intermediate capsids on potency, an AAV preparation was separated into fractions enriched for full, intermediate, or empty capsids. Using a matrix of in vitro (infectivity, gene expression, biological activity) and in vivo potency assays to determine potency as a function of capsid content, our results indicate that while intermediate capsids contribute to the vector genome titer of the product and are equally as infectious as full capsids, they do not contribute to the potency of the AAV product. This study confirms the criticality of reducing and controlling the level of intermediate capsids to ensure a more efficacious AAV product.

Sex differences in functional connectivity and the predictive role of the connectome-based predictive model in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline. Sex differences in the progression of AD exist, but the neural mechanisms are not well understood. The purpose of the current study was to explore sex differences in brain functional connectivity (FC) at different stages of AD and their predictive ability on Montreal Cognitive Assessment (MoCA) scores using connectome-based predictive modeling (CPM). Resting-state functional magnetic resonance imaging was collected from 81 AD patients (44 females), 78 amnestic mild cognitive impairment patients (44 females), and 92 healthy controls (50 females). The FC analysis was conducted and the interaction effect between sex and group was investigated using two-factor variance analysis. The CPM was used to predict MoCA scores. There were sex-by-group interaction effects on FC between the left dorsolateral superior frontal gyrus and left middle temporal gyrus, left precuneus and right calcarine fissure surrounding cortex, left precuneus and left middle occipital gyrus, left middle temporal gyrus and left precentral gyrus, and between the left middle temporal gyrus and right cuneus. In the CPM, the positive network predictive model significantly predicted MoCA scores in both males and females. There were significant sex-by-group interaction effects on FC between the left precuneus and left middle occipital gyrus, and between the left middle temporal gyrus and right cuneus could predict MoCA scores in female patients. Our results suggest that there are sex differences in FC at different stages of AD. The sex-specific FC can further predict MoCA scores at individual level.

Age- and Sex-Specific MR-Feature Tracking Reference Values of Right Atrial Deformation in Healthy Adults.

BACKGROUND: Although right atrial (RA) myocardial deformation has important implications for patient diagnosis, prognosis, and risk stratification, its implementation in clinical practice has been hampered by limited normal reference values, especially in Asian populations. PURPOSE: To establish age- and sex-specific reference values for RA strain, strain rate (SR), and displacement based on a large sample of healthy Chinese adults using MR-feature tracking (MR-FT). STUDY TYPE: Retrospective. POPULATION: 524 healthy Chinese adults (287 male; mean age 43.7 ± 11.9 years). FIELD STRENGTH/SEQUENCE: 1.5T/balanced steady-state free precession. ASSESSMENT: RA deformation parameters, including reservoir, conduit, and booster strain (εs, εe, and εa), peak positive, early negative, and late negative SR (SRs, SRe, and SRa), and total, passive, and active displacement (Ds, De, and Da), were assessed using MR-FT. STATISTICAL TESTS: Student's t-test, one-way ANOVA, coefficients of determination (r2 ), intraclass correlation coefficients (ICC), and Bland-Altman plots. A P value <0.05 was considered significant. RESULTS: Women demonstrated significantly greater magnitudes of RA deformation parameters than men: εs (57.4% ± 15.1% vs. 44.3% ± 12.6%), εe (37.5% ± 13.4% vs. 27.4% ± 10.9%), εa (19.9% ± 5.7% vs. 16.9% ± 5.0%), SRs (2.62 ± 0.88 sec-1 vs. 2.00 ± 0.63 sec-1 ), SRe (-2.98 ± 1.26 sec-1 vs. -2.16 ± 0.92 sec-1 ), SRa (-2.28 ± 0.75 sec-1 vs. -1.84 ± 0.62 sec-1 ), Ds (-7.80 ± 1.90 mm vs. -7.46 ± 1.70 mm), and De (-4.84 ± 1.31 mm vs. -4.49 ± 1.21 mm). For both sexes, aging was significantly associated with decreased RA reservoir and conduit function (εs, SRs, Ds, εe, SRe, and De), and with increased εa and Da. RA deformation measurements had good to excellent intraobserver and interobserver reproducibility, with ICCs ranging from to 0.790 to 0.972. DATA CONCLUSION: This study provides age- and sex-specific reference values of RA strain, SR, and displacement based on a large cohort of healthy Chinese adults using MR-FT. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

A smartwatch sphygmomanometer-based model for predicting short-term new-onset hypertension in individuals with high-normal blood pressure: a cohort study.

OBJECTIVES: The objective was to utilize a smartwatch sphygmomanometer to predict new-onset hypertension within a short-term follow-up among individuals with high-normal blood pressure (HNBP). METHODS: This study consisted of 3180 participants in the training set and 1000 participants in the validation set. Participants underwent both ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM) using a smartwatch sphygmomanometer. Multivariable Cox regressions were used to analyze cumulative events. A nomogram was constructed to predict new-onset hypertension. Discrimination and calibration were assessed using the C-index and calibration curve, respectively. RESULTS: Among the 3180 individuals with HNBP in the training set, 693 (21.8%) developed new-onset hypertension within a 6-month period. The nomogram for predicting new-onset hypertension had a C-index of 0.854 (95% CI, 0.843-0.867). The calibration curve demonstrated good agreement between the nomogram's predicted probabilities and actual observations for short-term new-onset hypertension. In the validate dataset, during the 6-month follow-up, the nomogram had a good C-index of 0.917 (95% CI, 0.904-0.930) and a good calibration curve. As the score increased, the risk of new-onset hypertension significantly increased, with an HR of 8.415 (95% CI: 5.153-13.744, p = .000) for the middle-score vs. low-score groups and 86.824 (95% CI: 55.071-136.885, p = .000) for the high-score vs. low-score group. CONCLUSIONS: This study provides evidence for the use of smartwatch sphygmomanometer to monitor blood pressure in individuals at high risk of developing new-onset hypertension in the near future. TRIAL REGISTRATION: ChiCTR2200057354.

Integrating UPLC-QTOF-MS/MS and UPLC-DAD to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on the overall quality of three Si-Wu-Tang formulations.

INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

Rationality of the ethanol precipitation process in modern preparation production of Zishui-Qinggan decoction evaluated by integrating UPLC-QTOF-MS/MS-based chemical profiling/serum pharmacochemistry and network pharmacology.

INTRODUCTION: Zishui-Qinggan decoction (ZQD) is a classical traditional Chinese medicine formula (TCMF) for alleviating menopausal symptoms (MPS) induced by endocrine therapy in breast cancer patients. In the production of TCMF modern preparations, ethanol precipitation (EP) is a commonly but not fully verified refining process. OBJECTIVES: Chemical profiling/serum pharmacochemistry and network pharmacology approaches were integrated for exploring the rationality of the EP process in the production of ZQD modern preparations. MATERIAL AND METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) was applied to identify the chemical profiles and absorbed components of ZQD. Network pharmacology was used to identify targets and pathways related to MPS-relieving efficacy. RESULTS: The chemicals of ZQDs without/with EP process (referred to as ZQD-W and ZQD-W-P, respectively) were qualitatively similar with 89 and 87 components identified, respectively, but their relative contents were different; 51 components were detectable in the serum of rats orally administered with ZQD-W, whereas only 19 were detected in that administered with ZQD-W-P. Key targets, such as AKT1, and pathways, such as the PI3K-Akt signalling pathway, affected by ZQD-W and ZQD-W-P were similar, while the neuroactive ligand-receptor interaction pathway among others and the MAPK signalling pathway among others were specific pathways affected by ZQD-W and ZQD-W-P, respectively. The specifically absorbed components of ZQD-W could combine its specific key targets. CONCLUSION: The EP process quantitatively altered the chemical profiles of ZQD, subsequently affected the absorbed components of ZQD, and then affected the key targets and pathways of ZQD for relieving MPS. The EP process might result in variation of the MPS-relieving efficacy of ZQD, which deserves further in vivo verification.

Environmental enrichment improves behaviors rather than the growth and physiology of rock bream Oplegnathus fasciatus.

Environmental enrichment has the potential to improve the welfare and post-release survival of hatchery fish stocked for conservation purposes. However, the effectiveness of environmental enrichment is partly dependent on the fish species, life stage, and specific enrichment structure used. To enhance the effectiveness of environmental enrichment, it is crucial to focus on characteristic differences in enrichment structures, such as type and level. This study investigated how differences in enrichment type and level affected physiological and behavioral aspects of the welfare of pre-release juvenile rock bream Oplegnathus fasciatus by evaluating growth performance, basal and stressed cortisol levels, antioxidant enzyme activities, and exploratory behaviors regarding anxiety and flexibility. Fish were reared for 4 weeks in different enrichment treatments: barren, low-level cover structure, high-level cover structure, low-level interference structure (LI), and high-level interference structure (HI). The results revealed that fish reared with the LI treatment showed less anxiety and greater flexibility with respect to exploratory behaviors, without oxidative damage being detected. Despite exhibiting less anxiety as well, fish reared in the HI treatment had oxidative damage, indicated by lower superoxide dismutase activity, compared to those in the barren treatment. In addition, none of these enrichment structures enhanced growth performance or mitigate chronic and acute stress responses. Overall, the low-level interference structure may be more favorable in promoting the behavioral welfare of the fish. Application of this type and level of enrichment may increase the survival of the hatchery fish after release, which is critical to stocking success.

Okra extract alleviates lipopolysaccharide-induced inflammation response through the regulation of bile acids, the receptor-mediated pathway, and gut microbiota.

BACKGROUND: Okra contains flavonoids and vitamin C as antioxidants and it contains polysaccharides as immunomodulators. Flavonoids regulate the inflammatory response in mice and may be related to gut microbiota. This study therefore aimed to investigate the impact of okra extract (OE) on inflammation in mice and to elucidate its underlying mechanism. METHOD: Forty male Kunming (KM) mice were categorized into four groups: the control (CON) group, the lipopolysaccharide stimulation (LPS) group, the 5 mg mL-1 OE intervention (LPS + OE) group, and the 5 mg mL-1 OE supplementation plus mixed antibiotics (LPS + OE + ABX) group. RESULTS: The results showed that, compared with the OE group, the expression of inflammatory signaling pathway genes was upregulated and gut barrier genes were inhibited in the OE + ABX group. The Fxr receptor was activated and the abundance of Akkermansia was increased after OE supplementation, whereas the effect was reversed in the OE + ABX group. Meanwhile, Fxr was correlated positively with Akkermansia. CONCLUSION: The OE supplementation alleviated the inflammatory response in mice under LPS stimulation, accompanied by changes in gut microbiota and bile acid receptors, whereas the addition of antibiotics caused a disturbance to the gut microbiota in the OE group, thus reducing the effect of OE in alleviating the inflammatory response. © 2024 Society of Chemical Industry.

Systems genetics of the Drosophila metabolome.

How effects of DNA sequence variants are transmitted through intermediate endophenotypes to modulate organismal traits remains a central question in quantitative genetics. This problem can be addressed through a systems approach in a population in which genetic polymorphisms, gene expression traits, metabolites, and complex phenotypes can be evaluated on the same genotypes. Here, we focused on the metabolome, which represents the most proximal link between genetic variation and organismal phenotype, and quantified metabolite levels in 40 lines of the Drosophila melanogaster Genetic Reference Panel. We identified sex-specific modules of genetically correlated metabolites and constructed networks that integrate DNA sequence variation and variation in gene expression with variation in metabolites and organismal traits, including starvation stress resistance and male aggression. Finally, we asked to what extent SNPs and metabolites can predict trait phenotypes and generated trait- and sex-specific prediction models that provide novel insights about the metabolomic underpinnings of complex phenotypes.

Gene expression networks in the Drosophila Genetic Reference Panel.

A major challenge in modern biology is to understand how naturally occurring variation in DNA sequences affects complex organismal traits through networks of intermediate molecular phenotypes. This question is best addressed in a genetic mapping population in which all molecular polymorphisms are known and for which molecular endophenotypes and complex traits are assessed on the same genotypes. Here, we performed deep RNA sequencing of 200 Drosophila Genetic Reference Panel inbred lines with complete genome sequences and for which phenotypes of many quantitative traits have been evaluated. We mapped expression quantitative trait loci for annotated genes, novel transcribed regions, transposable elements, and microbial species. We identified host variants that affect expression of transposable elements, independent of their copy number, as well as microbiome composition. We constructed sex-specific expression quantitative trait locus regulatory networks. These networks are enriched for novel transcribed regions and target genes in heterochromatin and euchromatic regions of reduced recombination, as well as genes regulating transposable element expression. This study provides new insights regarding the role of natural genetic variation in regulating gene expression and generates testable hypotheses for future functional analyses.

Transcriptomics reveals the molecular mechanisms of flesh colour differences in eggplant (Solanum melongena).

BACKGROUND: Fruit flesh colour is not only an important commodity attribute of eggplant but is also closely related to maturity. However, very little is known about its formation mechanism in eggplant. RESULTS: Two inbred lines of eggplant, green 'NC7' and white 'BL', were used in this study to explain the differences in flesh colour. Transcriptome sequencing results revealed a total of 3304 differentially expressed genes (DEGs) in NC7 vs. BL. Of the DEGs obtained, 2050 were higher and 1254 were lower in BL. These DEGs were annotated to 126 pathways, where porphyrin and chlorophyll metabolism, flavonoid biosynthesis, and photosynthesis-antenna proteins play vital roles in the colour formation of eggplant flesh. At the same time, Gene Ontology (GO) enrichment significance analysis showed that a large number of unigenes involved in the formation of chloroplast structure were lower in BL, which indicated that the formation of chloroplasts in white-fleshed eggplant was blocked. This was confirmed by transmission electron microscopy (TEM), which found only leucoplasts but no chloroplasts in the flesh cells of white-fleshed eggplant. Several genes encoding ERF and bHLH transcription factors were predicted to participate in the regulation of chlorophyll biosynthetic genes. CONCLUSIONS: The results of this study indicated that differences in the gene expression of the chlorophyll metabolic pathway were the main cause of the different flesh colour formations. These findings will increase our understanding of the genetic basis in eggplant flesh colors formation mechanism.

Deep Learning-based Prediction of Percutaneous Recanalization in Chronic Total Occlusion Using Coronary CT Angiography.

Background CT is helpful in guiding the revascularization of chronic total occlusion (CTO), but manual prediction scores of percutaneous coronary intervention (PCI) success have challenges. Deep learning (DL) is expected to predict success of PCI for CTO lesions more efficiently. Purpose To develop a DL model to predict guidewire crossing and PCI outcomes for CTO using coronary CT angiography (CCTA) and evaluate its performance compared with manual prediction scores. MATERIALS AND METHODS: Participants with CTO lesions were prospectively identified from one tertiary hospital between January 2018 and December 2021 as the training set to develop the DL prediction model for PCI of CTO, with fivefold cross validation. The algorithm was tested using an external test set prospectively enrolled from three tertiary hospitals between January 2021 and June 2022 with the same eligibility criteria. All participants underwent preprocedural CCTA within 1 month before PCI. The end points were guidewire crossing within 30 minutes and PCI success of CTO.Results A total of 534 participants (mean age, 57.7 years ± 10.8 [SD]; 417 [78.1%] men) with 565 CTO lesions were included. In the external test set (186 participants with 189 CTOs), the DL model saved 85.0% of the reconstruction and analysis time of manual scores (mean, 73.7 seconds vs 418.2-466.9 seconds) and had higher accuracy than manual scores in predicting guidewire crossing within 30 minutes (DL, 91.0%; CT Registry of Chronic Total Occlusion Revascularization, 61.9%; Korean Multicenter CTO CT Registry [KCCT], 68.3%; CCTA-derived Multicenter CTO Registry of Japan (J-CTO), 68.8%; P < .05) and PCI success (DL, 93.7%; KCCT, 74.6%; J-CTO, 75.1%; P < .05). For DL, the area under the receiver operating characteristic curve was 0.97 (95% CI: 0.89, 0.99) for the training test set and 0.96 (95% CI: 0.90, 0.98) for the external test set. Conclusion The DL prediction model accurately predicted the percutaneous recanalization outcomes of CTO lesions and increased the efficiency of noninvasively grading the difficulty of PCI. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Pundziute-do Prado in this issue.

Natural genetic variation in a dopamine receptor is associated with variation in female fertility in Drosophila melanogaster.

Fertility is a major component of fitness but its genetic architecture remains poorly understood. Using a full diallel cross of 50 Drosophila Genetic Reference Panel inbred lines with whole genome sequences, we found substantial genetic variation in fertility largely attributable to females. We mapped genes associated with variation in female fertility by genome-wide association analysis of common variants in the fly genome. Validation of candidate genes by RNAi knockdown confirmed the role of the dopamine 2-like receptor (Dop2R) in promoting egg laying. We replicated the Dop2R effect in an independently collected productivity dataset and showed that the effect of the Dop2R variant was mediated in part by regulatory gene expression variation. This study demonstrates the strong potential of genome-wide association analysis in this diverse panel of inbred strains and subsequent functional analyses for understanding the genetic architecture of fitness traits.

Healthy Adult Left and Right Ventricular Torsion and Torsion Rates With MR-Feature Tracking.

BACKGROUND: The clinical value of myocardial torsion quantification in prognostic assessment and risk stratification of various cardiovascular diseases is gradually being recognized. However, normal values of left and right ventricular (LV and RV) torsion and torsion rates (TRs) have not been fully determined, and their correlation with age and gender has not been well studied. PURPOSE: To establish normal ranges of biventricular torsion, peak systolic and diastolic TRs using magnetic resonance feature tracking (MR-FT) technique based on a large sample of healthy adults, and further investigate their relationship with age and gender. STUDY TYPE: Retrospective. POPULATION: 566 Healthy adults (312 males, aged 43 ± 10 years; 254 females, aged 43 ± 11 years). FIELD STRENGTH/SEQUENCE: 1.5T/gradient echo. ASSESSMENT: Biventricular torsion, peak systolic, and diastolic TRs. STATISTICAL TESTS: Shapiro-Wilk test, Student's t-test, Mann-Whitney-U test, linear regression, intraclass correlation coefficient, Bland-Altman analysis. Differences were regarded as statistically significant at P < 0.05. RESULTS: Women demonstrated greater magnitudes of left ventricle (LV) torsion (1.23 ± 0.44 vs. 1.00 ± 0.42°/cm), peak systolic TR (9.69 ± 3.70 vs. 8.27 ± 3.73°/cm*sec), peak diastolic TR (-7.78 ± 2.82 vs. -6.06 ± 2.44°/cm*sec), and RV torsion (2.20 ± 1.23 vs. 1.65 ± 1.11°/cm*sec), peak systolic TR (16.07 ± 8.18 vs. 12.62 ± 7.08°/cm*sec), peak diastolic TR (-15.39 ± 6.53 vs. -11.70 ± 6.03°/cm*sec). For both genders, the magnitudes of LV and RV torsion, peak systolic, and diastolic TRs increased linearly with age. All the measurements of biventricular torsion, peak systolic and diastolic TRs achieved good to excellent intraobserver and interobserver reproducibility, with all intraclass correlation coefficients >0.70. DATA CONCLUSION: The present study systematically provided age- and sex-stratified reference values for LV and RV torsion and TRs using MR-FT technique. Women and aging are associated with greater magnitudes of biventricular torsion, peak systolic, and diastolic TRs. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Sex-dependent changes in emotional memory associated with cerebral blood flow alterations during Alzheimer's disease progression.

PURPOSE: Sex differences in Alzheimer's disease (AD) progression provide clues to pathogenesis and better patient management. We examined sex differences in emotional memory among AD patients, amnestic mild cognitive impairment (aMCI) patients, and healthy controls (HCs) as well as potential associations with altered regional cerebral blood flow (rCBF). METHODS: The recognition memory task with emotional pictures was applied to evaluate enhancement of emotional memory (EEM) and 3D pseudo-continuous arterial spin labeling MRI was performed to measure the rCBF in 74 AD patients (41 females), 74 aMCI patients (45 females), and 74 HCs (43 females). Group differences in EEM were tested by two-way analysis of covariance (ANCOVA) with repeated measures. The main effects of clinical group and sex as well as group × sex interactions on rCBF were assessed by two-way ANCOVA. Correlation analyses were conducted to investigate associations between EEM and rCBF. RESULTS: With disease progression, EEM gradually disappeared. Among aMCI patients, females exhibited a greater index of recollection (Pr) for positive/high-arousal and negative/low-arousal pictures versus neutral pictures (P = 0.005, P = 0.003), while males exhibited a greater Pr for negative/high-arousal versus neutral pictures (P = 0.001). There were significant sex × group effects on rCBF in left inferior parietal, supramarginal, superior temporal and middle temporal gyri, and rCBF of left inferior parietal gyrus was correlated with Pr for positive/high-arousal pictures among female aMCI patients (r = 0.584, q = 0.005). CONCLUSION: Males and females exhibit distinct changes in EEM associated with altered rCBF, which should be considered in future neuroimaging studies.

One-step integrated coronary-carotid-cerebral computed tomography angiography to evaluate cardiovascular and cerebrovascular atherosclerosis.

PURPOSE: This study aims to develop a low-radiation dose, one-step integrated coronary-carotid-cerebral computed tomography angiography (ICCC-CTA) technique to analyze the relationship between cardiovascular and cerebrovascular atherosclerosis and evaluate the risk factors of plaque to provide an early-stage treatment to patients and reduce vascular events. METHODS: A total of 300 consecutive asymptomatic patients with cardiovascular risk factors who underwent ICCC-CTA were enrolled in this prospective study. The association between coronary and carotid-cerebrovascular atherosclerosis was assessed. The primary cardiovascular risk factors for various plaque types in cardiovascular or cerebrovascular disease were evaluated using multivariate analysis. RESULTS: Among 300 patients, 189 (63%) had plaques in their coronary and cerebral arteries. The presence of calcified and mixed plaques in the carotid-cerebral and coronary arteries was strongly correlated (χ2 = 20.71, P = 0.001; χ2 = 8.96, P = 0.003, respectively). Multivariate logistic regression analysis revealed that abnormal blood glucose [OR = 1.44, 95% CI 0.12-0.62, P = 0.01] and abnormal total cholesterol [OR = 1.28, 95% CI 0.07-0.46, P = 0.01] are risk factors in all the models in the coronary artery, non-calcified plaque group. Abnormal blood glucose [OR = 1.43, 95% CI 0.11-0.61, P = 0.01] and abnormal systolic blood pressure [OR = 1.02, 95% CI 0.01-0.04, P = 0.02] are risk factors in all the models in the coronary artery calcified plaque group. Abnormal blood glucose level [OR = 1.44, 95% CI = 0.12-0.62, P = 0.01] was only a risk factor in the non-calcified plaque carotid-cerebral artery group. CONCLUSIONS: We confirm that elevated blood glucose and total cholesterol levels are associated with coronary and carotid-cerebrovascular plaques using the novel one-step low dose cerebral-carotid-cardiac CTA technique. These findings will provide insights for further studies focusing on developing low-radiation dose one-step ICCC-CTA to screen cardiovascular/cerebrovascular plaques in general population with cardiovascular risk factors. ADVANCES IN KNOWLEDGE: We developed a low-radiation dose, one-step ICCC-CTA technique to detect cardiovascular and cerebrovascular atherosclerosis. We evaluated the risk factors for plaque burden for the early treatment and reduction of vascular events. These findings supported the development of low-radiation dose one-step ICCC-CTA to screen for cardiovascular/cerebrovascular disease in general population with cardiovascular risk factors.

Education reduces cognitive dysfunction in Alzheimer's disease by changing regional cerebral perfusion: An in-vivo arterial spin labeling study.

OBJECTIVE: Formal education and other cognitive challenges influence brain structure and improve function. It is believed that cognitive activities create a cognitive reserve (CR) that can slow the decline due to aging and neurodegenerative diseases. This study investigated alterations of regional cerebral blood flow (rCBF) associated with high and low CR in different stages of Alzheimer's disease (AD) and examined whether rCBF alteration mediates the relationship between education and cognitive performance. METHODS: Patients with AD or amnestic mild cognitive impairment (aMCI) and healthy controls were divided into low cognitive reserve (LCR) and high cognitive reserve (HCR) subgroups according to median of education years (≤ 9 vs. > 9 years). The final study population included 89 AD patients (67 LCR, 22 HCR), 74 aMCI patients (44 LCR, 30 HCR), and 66 healthy controls (29 LCR, 37 HCR). All subjects were examined by arterial spin labeling magnetic resonance imaging and a neurocognitive test battery. rCBF was compared among groups by two-way analysis of variance. Mediation analyses were used to explore the relationships among education, rCBF, and cognitive test scores. RESULTS: There were significant interaction effects of disease state (AD, aMCI, HC) and education level (LCR, HCR) on CBF in right hippocampus, posterior cingulate cortex, and right inferior parietal cortex (R_IPC). Education regulated episodic memory score by influencing right hippocampal CBF in HC_HCR and aMCI_HCR subgroups. CONCLUSION: Our results indicate that the protective effect of education against cognitive dysfunction in early-stage AD is mediated at least partially by altered CBF in right hippocampus.