Expressions of sugar transporters/trehalases in relation to PTTH-stimulated ecdysteroidogenesis in the silkworm, Bombyx mori.

The prothoracic gland (PG) is the source of ecdysteoids in larval insects. Although numerous studies have been conducted on signaling networks involved in prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis in PGs, less is known about regulation of metabolism in PGs. In the present study, we investigated correlations between expressions of sugar transporter (St)/trehalase (Treh) genes and PTTH-stimulated ecdysteroidogenesis in Bombyx mori PGs. Our results showed that in vitro PTTH treatment stimulated expression of the St1 gene, but not other transporter genes. Expression of the Treh1 gene was also stimulated by PTTH treatment. An immunoblotting analysis showed that St1 protein levels in Bombyx PGs increased during the later stage of the last larval instar and were not affect by PTTH treatment. PTTH treatment enhanced Treh enzyme activity in a time-dependent manner. Blocking either extracellular signal-regulated kinase (ERK) signaling with U0126 or phosphatidylinositol 3-kinase (PI3K) signaling with LY294002 decreased PTTH-stimulated Treh enzyme activity, indicating a link from the ERK and PI3K signaling pathways to Treh activity. Treatment with the Treh inhibitor, validamycin A, blocked PTTH-stimulated Treh enzyme activity and partially inhibited PTTH-stimulated ecdysteroidogenesis. Treatment with either a sugar transport inhibitor (cytochalasin B) or a specific glycolysis inhibitor (2-deoxy-D-glucose, 2-DG) partially inhibited PTTH-stimulated ecdysteroidogenesis. Taken together, these results indicate that increased expressions of St1/Treh1 and Treh activity, which lie downstream of PTTH signaling, are involved in PTTH stimulation in B. mori PGs.

The Surgical Strategy Cerebrospinal Fluid Decompression Facilitates Outcomes of Adults with Chiari Malformation Type I: An Observational, Real-World, Single-Center Study of 528 Patients.

OBJECTIVE: We designed this study to introduce the surgical strategy cerebrospinal fluid (CSF) decompression in treatment of Chiari malformation type I and compared CSF decompression with other surgical strategies to provide a solid basis for patient counseling. METHODS: The study enrolled 528 consecutive patients with CMI who underwent surgical interventions from 2012 to 2022. The surgical strategy for these patients was bony and dural decompression, anatomical reduction of herniated tonsils, or CSF decompression. Short-term results were determined after 3 months; long-term outcomes were evaluated at last follow-up (at least 18 months). RESULTS: CSF decompression was independently associated with better long- or short-term primary outcomes than anatomical reduction of herniated tonsils or bony and dural decompression (P < 0.001). Compared with short-term, the long-term outcomes were better in patients who underwent CSF decompression (P = 0.035), but were worse in patients with bony and dural decompression (P = 0.03). Specific surgical techniques cannot affect the long- and short-term outcomes of patients with Chiari malformation type I. CSF decompression provided better long-term syringomyelia improvement than short-term (181/218, 83% vs. 169/218, 77.5%; P < 0.001). CONCLUSIONS: CSF decompression, but not a specific surgical technique or operative method, was associated with favorable neurological outcomes in ADULT patients with Chiari malformation type I. The surgical technique and operative method should be selected according to the characteristics of each patient and the intraoperative condition to normalize CSF circulation at the craniovertebral junction area. The intraoperative target, smooth CSF flow out from the fourth ventricle and in to the bilateral Luschka foramina, could be observed.

Emergence and reconfiguration of modular structure for artificial neural networks during continual familiarity detection.

Advances in artificial intelligence enable neural networks to learn a wide variety of tasks, yet our understanding of the learning dynamics of these networks remains limited. Here, we study the temporal dynamics during learning of Hebbian feedforward neural networks in tasks of continual familiarity detection. Drawing inspiration from network neuroscience, we examine the network's dynamic reconfiguration, focusing on how network modules evolve throughout learning. Through a comprehensive assessment involving metrics like network accuracy, modular flexibility, and distribution entropy across diverse learning modes, our approach reveals various previously unknown patterns of network reconfiguration. We find that the emergence of network modularity is a salient predictor of performance and that modularization strengthens with increasing flexibility throughout learning. These insights not only elucidate the nuanced interplay of network modularity, accuracy, and learning dynamics but also bridge our understanding of learning in artificial and biological agents.

High expression levels of centromere protein O participates in cell proliferation of human ovarian cancer.

Ovarian cancer is a common malignant tumor in women, with a high mortality rate ranking first among gynecological tumors. Currently, there is insufficient understanding of the causes, pathogenesis, recurrence and metastasis of ovarian cancer, and early diagnosis and treatment still face great challenges. The sensitivity and specificity of existing ovarian cancer screening methods are still unsatisfactory. Centromere protein O (CENP-O) is a recently discovered structural centromere protein that is involved in cell death and is essential for spindle assembly, chromosome separation, and checkpoint signaling during mitosis. The abnormal high expression of CENP-O was detected in various tumors such as bladder cancer and gastric cancer, and it participates in the regulation of tumor cell proliferation. In this study, we detect the expression abundance of CENP-O mRNA in different ovarian cancer cells ( ES-2, A2780, Caov-3, OVCAR-3 and SK-OV-3). The biological function changes of cell proliferation and apoptosis were detected and the role of CENP-O in ovarian cancer cell proliferation and apoptosis was explored by knocking down the expression of CENP-O gene. The results showed that CENP-O gene was significantly expressed in 5 types of ovarian cancer cell lines. After knocking down the CENP-O gene, the proliferation and cloning ability of ovarian cancer cells decreased, and the apoptosis increased. This study indicates that CENP-O has the potential to be a molecular therapeutic target, and downregulating the expression of CENP-O gene can break the unlimited proliferation ability of cancer cells and promote their apoptosis, providing a foundation and new ideas for subsequent molecular mechanism research and targeted therapy.

Ultrahigh-Flux Water Nanopumps Generated by Asymmetric Terahertz Absorption.

Controlling active transport of water through membrane channels is essential for advanced nanofluidic devices. Despite advancements in water nanopump design using techniques like short-range invasion and subnanometer-level control, challenges remain facilely and remotely realizing massive waters active transport. Herein, using molecular dynamic simulations, we propose an ultrahigh-flux nanopump, powered by frequency-specific terahertz stimulation, capable of unidirectionally transporting massive water through asymmetric-wettability membrane channels at room temperature without any external pressure. The key physics behind this terahertz-powered water nanopump is revealed to be the energy flow resulting from the asymmetric optical absorption of water.

Downregulation of miR-503-5p Promotes the Development of Pancreatic Cancer by Targeting Cyclin E2.

This study aimed to elucidate the role of microRNA-503 (miR-503) in pancreatic cancer (PC) progression and the underlying regulatory mechanisms. We acquired miR-503-3p and miR-503-5p expression data along with survival times of PC and normal samples from the UCSC Xena database. Using the t-test, we compared the expression of miR-503-3p and miR-503-5p between PC and normal samples, and evaluated their prognostic significance via Kaplan-Meier survival analysis. The expression of miR-503-5p in PC cells was detected by quantitative PCR. We subsequently overexpressed miR-503-5p in PC cells and examined cell viability, apoptosis, and migration through CCK8 assay, flow cytometry, and Transwell assay, respectively. Potential functional targets were identified using miRTarBase and validated by dual-luciferase reporter assay. Both miR-503-3p and miR-503-5p expression were found to be downregulated in PC; however, only miR-503-5p was linked to cancer prognosis based on public data. In vitro experiments demonstrated that overexpression of miR-503-5p substantially decreased cell viability, induced apoptosis, caused G0/G1 arrest, and inhibited cell migration. miR-503-5p was found to target cyclin E2 (CCNE2), and overexpression of CCNE2 could counteract the effects of miR-503-5p on PC cells. Conclusion: The downregulation of miR-503-5p enhances the progression of PC by targeting CCNE2. The detection of miR-503-5p expression may provide valuable insights for the prevention and prognostic evaluation of PC.

Self-supervised learning for medical image data with anatomy-oriented imaging planes.

Self-supervised learning has emerged as a powerful tool for pretraining deep networks on unlabeled data, prior to transfer learning of target tasks with limited annotation. The relevance between the pretraining pretext and target tasks is crucial to the success of transfer learning. Various pretext tasks have been proposed to utilize properties of medical image data (e.g., three dimensionality), which are more relevant to medical image analysis than generic ones for natural images. However, previous work rarely paid attention to data with anatomy-oriented imaging planes, e.g., standard cardiac magnetic resonance imaging views. As these imaging planes are defined according to the anatomy of the imaged organ, pretext tasks effectively exploiting this information can pretrain the networks to gain knowledge on the organ of interest. In this work, we propose two complementary pretext tasks for this group of medical image data based on the spatial relationship of the imaging planes. The first is to learn the relative orientation between the imaging planes and implemented as regressing their intersecting lines. The second exploits parallel imaging planes to regress their relative slice locations within a stack. Both pretext tasks are conceptually straightforward and easy to implement, and can be combined in multitask learning for better representation learning. Thorough experiments on two anatomical structures (heart and knee) and representative target tasks (semantic segmentation and classification) demonstrate that the proposed pretext tasks are effective in pretraining deep networks for remarkably boosted performance on the target tasks, and superior to other recent approaches.

Enhancing neural encoding models for naturalistic perception with a multi-level integration of deep neural networks and cortical networks.

Cognitive neuroscience aims to develop computational models that can accurately predict and explain neural responses to sensory inputs in the cortex. Recent studies attempt to leverage the representation power of deep neural networks (DNNs) to predict the brain response and suggest a correspondence between artificial and biological neural networks in their feature representations. However, typical voxel-wise encoding models tend to rely on specific networks designed for computer vision tasks, leading to suboptimal brain-wide correspondence during cognitive tasks. To address this challenge, this work proposes a novel approach that upgrades voxel-wise encoding models through multi-level integration of features from DNNs and information from brain networks. Our approach combines DNN feature-level ensemble learning and brain atlas-level model integration, resulting in significant improvements in predicting whole-brain neural activity during naturalistic video perception. Furthermore, this multi-level integration framework enables a deeper understanding of the brain's neural representation mechanism, accurately predicting the neural response to complex visual concepts. We demonstrate that neural encoding models can be optimized by leveraging a framework that integrates both data-driven approaches and theoretical insights into the functional structure of the cortical networks.

Choroid plexus volume enlargement in first-episode antipsychotic-naïve schizophrenia.

Investigation of the choroid plexus in schizophrenia has seen growing interest due to its role in the interaction between neuroinflammation and brain dysfunction. Most previous studies included treated and long-term ill patients, while antipsychotics and illness course might both affect the choroid plexus. Here, we recruited first-episode antipsychotic-naïve schizophrenia patients, performed high-resolution structural brain scan and manually extracted choroid plexus volume. Choroid plexus volume was compared between patients and healthy controls after controlling for age, sex and intracranial volume. Age and sex effects were examined on choroid plexus volume in patient and healthy control groups respectively. In patients, we also examined the correlation of choroid plexus volume with volume measures of cortical and subcortical gray matter, white matter, lateral ventricular as well as symptom severity and cognitive function. Schizophrenia patients showed significantly enlarged choroid plexus volume compared with healthy controls. Choroid plexus volume was positively correlated with age in only patient group and we found significantly larger choroid plexus volumes in males than females in both patient and healthy control groups, while the sex effects did not differ between groups. Choroid plexus volume was only found correlated with lateral ventricular volume among the brain volume measures. No significant correlation between choroid plexus volume and clinical ratings or cognitive performance was observed. Without potential confounding effects of pharmacotherapy or illness course, our findings indicated the enlargement of choroid plexus in schizophrenia might be an enduring trait for schizophrenia.

Pseudopolymorphic Phase Engineering for Improved Thermoelectric Performance in Copper Sulfides.

Polymorphism (and its extended form - pseudopolymorphism) in solids is ubiquitous in mineralogy, crystallography, chemistry/biochemistry, materials science, and the pharmaceutical industries. Despite the difficulty of controlling (pseudo-)polymorphism, the realization of specific (pseudo-)polymorphic phases and associated boundary structures is an efficient route to enhance material performance for energy conversion and electromechanical applications. Here, this work applies the pseudopolymorphic phase (PP) concept to a thermoelectric copper sulfide, Cu2- x S (x ≤ 0.25), via CuBr2 doping. A peak ZT value of 1.25 is obtained at 773 K in Cu1.8 S + 3 wt% CuBr2 , which is 2.3 times higher than that of a pristine Cu1.8 S sample. Atomic-resolution scanning transmission electron microscopy confirms the transformation of pristine Cu1.8 S low digenite into PP-engineered high digenite, as well as the formation of (semi-)coherent interfaces between different PPs, which is expected to enhance phonon scattering. The results demonstrate that PP engineering is an effective approach for achieving improved thermoelectric performance in Cu-S compounds. It is also expected to be useful in other materials.

[Spatial-temporal Evolution of Ecological Vulnerability in Beijing-Tianjin-Hebei Region Based on PSRM Model].

As one of the three major urban agglomerations in China, the Beijing-Tianjin-Hebei Region has strong economic strength but its ecological fragility is very prominent. To pursue the comprehensive development of economy and ecology, it is very important to analyze the ecological environment in the Beijing-Tianjin-Hebei Region. Here, the Beijing-Tianjin-Hebei Region was selected as the research area, and 19 indicators were selected to construct an evolution system based on the PSRM model. The temporal and spatial evolution characteristics of ecological vulnerability in the Beijing-Tianjin-Hebei Region were explored by combining the order relation method, CRITIC method, Theil index, and hot spot analysis, and the influencing factors were calculated via geographic detector. The results showed that:① the ecological vulnerability first increased and then decreased in the Beijing-Tianjin-Hebei Region. The vulnerable areas showed a northeast-southwest trend, and the ecological environment in the northeast and southwest regions was better than that in the central and southern regions. The area of slight vulnerability in 2014 increased by 6803.01 km2 compared with that in 2009. The area of mild vulnerability decreased by 130.41 km2, and the area of moderate vulnerability decreased by 26537.31 km2 compared with that in 2009. The areas of severe and extremely vulnerable status increased by 19512.9 km2 and 351.81 km2, respectively, compared with those in 2009. The habitat situation in the Beijing-Tianjin-Hebei Region improved significantly from 2014 to 2019. Compared with that in 2014, the areas of mild, moderate, severe, and extremely vulnerable decreased by 2248.29 km2, 2220.21 km2, 7988.67 km2, and 55.98 km2, respectively. The light area increased by 12513.15 km2 compared with that in 2014. ② According to the calculation results of the Theil index, the spatial correlation degree of ecological vulnerability in the Beijing-Tianjin-Hebei Region exhibited a V-shaped fluctuation, and the spatial pattern of the cold and hot areas was predominantly consistent with that of the vulnerability. ③ Biological abundance, PM10, and the human disturbance index had a significant influence on the spatial differentiation of ecological vulnerability in the Beijing-Tianjin-Hebei Region. Based on the results of ecological vulnerability analysis, some suggestions on the ecological environment and sustainable development in the Beijing-Tianjin-Hebei Region were proposed.

Network controllability of structural connectomes in the neonatal brain.

White matter connectivity supports diverse cognitive demands by efficiently constraining dynamic brain activity. This efficiency can be inferred from network controllability, which represents the ease with which the brain moves between distinct mental states based on white matter connectivity. However, it remains unclear how brain networks support diverse functions at birth, a time of rapid changes in connectivity. Here, we investigate the development of network controllability during the perinatal period and the effect of preterm birth in 521 neonates. We provide evidence that elements of controllability are exhibited in the infant's brain as early as the third trimester and develop rapidly across the perinatal period. Preterm birth disrupts the development of brain networks and altered the energy required to drive state transitions at different levels. In addition, controllability at birth is associated with cognitive ability at 18 months. Our results suggest network controllability develops rapidly during the perinatal period to support cognitive demands but could be altered by environmental impacts like preterm birth.

Prognostic role of the peritoneal cancer index in ovarian cancer patients who undergo cytoreductive surgery: a meta-analysis.

Advanced-stage ovarian cancer is usually associated with peritoneal carcinomatosis. This study evaluates the prognostic role of the Peritoneal Cancer Index (PCI) in predicting the survival of patients with ovarian cancer. A literature search was conducted in electronic databases (Google Scholar, PubMed, Ovid, and Science Direct) and study selection was based on precise eligibility criteria. Random-effects meta-analyses were performed to estimate survival with low and high PCI scores and to pool hazard ratios (HR) of survival between lower and higher PCI scores. A total of 20 studies (2588 patients) were included. Median follow-up was 39 months [95%CI: 25, 54]. Complete cytoreduction rate was 80% [95% CI: 73, 87]. The median PCI score was 11.3 [95% CI: 9.9, 12.7]. Median survival was 56.7 months [95% CI: 45.2, 68.2] with below and 28.8 months [95% CI: 23.0, 34.6] with above any PCI cutoff. Most studies used PCI cutoffs between 10 and 20. The median progression-free survival was 23.7 months [95% CI: 16.5, 30.8] with below and 11.9 months [95% CI: 5.9, 17.9] with above any PCI cutoff. 5-year survival rates were 61.3% [95% CI: 49.9, 72.8] with PCI<10 cutoffs, 21.7% [95% CI: 11.6, 31.8] with PCI>10 cutoffs, 50.1% [95% CI: 39.0, 61.2] with PCI<20 cutoffs, and 21.7% [95% CI: 16.2, 27.1] with PCI>20 cutoffs. Pooled analysis of HRs showed that a higher PCI score was associated with worse survival in both univariate (HR 2.14 [95%CI: 1.63, 2.66]) and multivariate (HR 1.10 [95% CI: 1.02, 1.18]) analyses. In a set of studies that used varying PCI cutoffs, the PCI has been found to have a significant inverse association with the survival of patients with advanced ovarian cancer who underwent cytoreductive surgery.

The Extract of Pinellia Ternata-Induced Apoptosis of Leukemia Cells by Regulating the Expression of Bax, Bcl-2 and Caspase-3 Protein Expression in Mice.

The study aims to lessen the monetary burden on patients and society by decreasing the price of proprietary drugs used in leukemia therapy. Flow cytometry, reverse transcription polymerase chain reaction, western blot, and a patient-derived xenograft mouse model were used to confirm the therapeutic effect of Pinellia ternata extract on leukemia. Three types of leukemia cells (K562, HL-60, and C8166 cell lines) were found to undergo early apoptosis (P ≤ .05) after being exposed to P. ternata extract, as measured by flow cytometry. Reverse transcription polymerase chain reaction results showed that P. ternata extract at both middle (300 µg/mL) and high (500 µg/mL) concentrations was able to down-regulate Bcl-2 and upregulate mRNA expression of Bax and caspase-3. In the patient-derived xenograft mouse model formed by BALB/c-nu/nu nude mice, immunohistochemistry indicated that P. ternata extract effectively suppressed the proliferation of leukemia cells. Therefore, P. ternata extract at 300 µg/mL and 500 µg/mL could effectively inhibit myeloid and lymphocytic leukemia cell proliferation and promote leukemia cell apoptosis by regulating Bax/Bcl-2 and caspase-3.

Signaling in cAMP-stimulated ecdysteroidogenesis in prothoracic glands of the silkworm, Bombyx mori.

In the present study, we investigated downstream pathways of cyclic adenosine monophosphate (cAMP) signaling (which is related to prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis) in Bombyx mori prothoracic glands (PGs). Results showed that treatment with either dibutyryl cAMP (dbcAMP) or 1-methyl-3-isobutylxanthine (MIX) inhibited phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and activated phosphorylation of the translational repressor, 4E-binding protein (4E-BP), a marker of target of rapamycin (TOR) signaling. A chemical activator of AMPK (5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside, AICAR) increased dbcAMP-inhibited AMPK phosphorylation and blocked dbcAMP-stimulated phosphorylation of 4E-BP, indicating that inhibition of AMPK phosphorylation lies upstream of dbcAMP-stimulated TOR signaling. Treatment of PGs with dbcAMP and MIX also stimulated phosphorylation of a 37-kDa protein, as recognized by a protein kinase C (PKC) substrate antibody, indicating that cAMP activates PKC signaling. Treatment with either LY294002 or AICAR did not affect dbcAMP-stimulated phosphorylation of the PKC-dependent 37-kDa protein, indicating that cAMP-stimulated PKC signaling is not related to phosphoinositide 3-kinase (PI3K) or AMPK. In addition, dbcAMP-stimulated ecdysteroidogenesis in PGs was partially inhibited by pretreatment with either LY294002, AICAR, or calphostin C. From these results, we concluded that AMPK/TOR/4E-BP and PKC pathways are involved in ecdysteroidogenesis of PGs stimulated by cAMP signaling in B. mori.

Expressions of sugar transporter genes during Bombyx mori embryonic development.

Sugar transporters (Sts) play important roles in controlling carbohydrate transport and are responsible for mediating the movement of sugars into cells. Few studies have been conducted on expressions of Sts during insect embryonic development. In the present study, we investigated temporal expressions of St genes during the embryonic diapause process in Bombyx mori. We found that in HCl-treated developing eggs, high gene expressions of trehalose transporter 1 (Tret1) were detected during middle and later embryonic development. St4 and St3 gene expressions gradually increased during the early stages, reached a small peak on Day 3, and large peaks were again detected on Day 7. However, in diapause eggs, expression levels of the Tret1, St4, and St3 genes all remained at low levels. Differential temporal changes in expressions of the Tret1, St4, and St3 genes found between diapause and HCl-treated eggs were further confirmed using nondiapause eggs. Our results showed that nondiapause eggs exhibited similar changing patterns as those of HCl-treated eggs, thus clearly indicating potential correlations between expressions of these genes and embryonic development. In addition, high gene expressions of Tret1 were also detected when dechorionated eggs were incubated in the medium. The addition of LY294002 (a specific phosphatidylinositol 3-kinase [PI3K] inhibitor) and U0126 (a mitogen-activated protein kinase/extracellular signal-regulated kinase [ERK] kinase [MEK] inhibitor) partially inhibited Tret1 gene expression in dechorionated eggs, but did not affect either ecdysteroid-phosphate phosphatase gene expression or ecdysteroid biosynthesis, clearly indicating that both PI3K and ERK are involved in increased gene expression of Tret1 that was independent of ecdysteroid levels. To our knowledge, this is the first comprehensive report to demonstrate the transcriptional regulation of St genes during embryonic development, thus providing useful information for a clearer understanding of insect egg diapause mechanisms.

Linked patterns of interhemispheric functional connectivity and microstructural characteristics of the corpus callosum in antipsychotic-naive first-episode schizophrenia.

OBJECTIVE: Many magnetic resonance imaging (MRI) studies have showed significant structural abnormalities of the corpus callosum (CC) and dysregulated interhemispheric functional connectivity (FC) in schizophrenia. Although the hemispheres are mainly linked through CC, few studies directly examined the relationship between aberrant interhemispheric FC and the white matter deficits of the CC in schizophrenia. METHODS: One hundred and sixty-nine antipsychotic-naive first-episode schizophrenia patients (AN-FES) and 214 healthy controls (HCs) were recruited. Diffusional and functional MRI data were obtained for each participant, and fractional anisotropy (FA) values of the five CC subregions and interhemispheric FC for each participant were acquired. Between-group differences in these metrics were compared using multivariate analysis of covariance (MANCOVA). Moreover, sparse canonical correlation analysis (sCCA) was conducted to explore correlations of fibers integrity of the CC subregions with dysregulated interhemispheric FC in patients. RESULTS: Compared with HCs, the patients with schizophrenia showed significantly reduced FA values of the CC subregions and dysregulated connectivity between two cerebral hemispheres. The canonical correlation coefficients identified five significant sCCA modes between FA and FC (r > 0.75, p < 0.001), suggesting strong relationships between FA values of the CC subregions and interhemispheric FC in patients. CONCLUSION: Our findings support a key role of CC in maintaining ongoing functional communication between two cerebral hemispheres, and suggest that microstructural changes of white matter fibers crossing different CC subregions may affect special interhemispheric FC in schizophrenia.

Associations of plaque morphology and location with Intraplaque neovascularization in the carotid artery by contrast-enhanced ultrasound imaging.

Objective: Intraplaque neovascularization (IPN) is a known indicator of plaque vulnerability, and is thus considered a predictor of stroke. The morphology and location of the carotid plaque may be correlated with plaque vulnerability. Therefore, our study aimed to examine the associations of carotid plaque morphology and location with IPN. Methods: A total of 141 patients with carotid atherosclerosis (mean age, 64.99 ± 10.96 years) who underwent carotid contrast-enhanced ultrasound (CEUS) between November 2021 and March 2022 were retrospectively analyzed. IPN was graded according to the presence and location of microbubbles within the plaque. The association of IPN grade with carotid plaque morphology and location was evaluated using ordered logistic regression. Results: Of the 171 plaques, 89 (52%) were IPN Grade 0, 21 (12.2%) were Grade 1, and 61 (35.6%) were Grade 2. IPN grade significantly associated with both plaque morphology and location, with higher grades observed among Type III morphology and common carotid artery plaques. Significant negative association was further shown between IPN grade and serum high-density lipoprotein cholesterol (HDL-C) level. Plaque morphology and location, and HDL-C remained significantly associated with IPN grade after adjusting for confounding factors. Conclusion: The location and morphology of carotid plaques were significantly associated with the IPN grade on CEUS, and therefore show potential as biomarkers for plaque vulnerability. Serum HDL-C was also identified as a protective factor against IPN, and may play a role in the management of carotid atherosclerosis. Our study provided a potential strategy for identification of vulnerable carotid plaques and elucidated the important imaging predictors of stroke.

Altered controllability of white matter networks and related brain function changes in first-episode drug-naive schizophrenia.

Understanding how structural connectivity alterations affect aberrant dynamic function using network control theory will provide new mechanistic insights into the pathophysiology of schizophrenia. The study included 140 drug-naive schizophrenia patients and 119 healthy controls (HCs). The average controllability (AC) quantifying capacity of brain regions/networks to shift the system into easy-to-reach states was calculated based on white matter connectivity and was compared between patients and HCs as well as functional network topological and dynamic properties. The correlation analysis between AC and duration of untreated psychosis (DUP) were conducted to characterize the controllability progression pattern without treatment effects. Relative to HCs, patients exhibited reduced AC in multiple nodes, mainly distributed in default mode network (DMN), visual network (VN), and subcortical regions, and increased AC in somatomotor network. These networks also had impaired functional topology and increased temporal variability in dynamic functional connectivity analysis. Longer DUP was related to greater reductions of AC in VN and DMN. The current study highlighted potential structural substrates underlying altered functional dynamics in schizophrenia, providing a novel understanding of the relationship of anatomic and functional network alterations.

Controllability of Functional Brain Networks and Its Clinical Significance in First-Episode Schizophrenia.

BACKGROUND AND HYPOTHESIS: Disrupted control of brain state transitions may contribute to the diverse dysfunctions of cognition, emotion, and behavior that are fundamental to schizophrenia. Control theory provides the rationale for evaluating brain state transitions from a controllability perspective, which may help reveal the brain mechanism for clinical features such as cognitive control deficits associated with schizophrenia. We hypothesized that brain controllability would be altered in patients with schizophrenia, and that controllability of brain networks would be related to clinical symptomatology. STUDY DESIGN: Controllability measurements of functional brain networks, including average controllability and modal controllability, were calculated and compared between 125 first-episode never-treated patients with schizophrenia and 133 healthy controls (HCs). Associations between controllability metrics and clinical symptoms were evaluated using sparse canonical correlation analysis. STUDY RESULTS: Compared to HCs, patients showed significantly increased average controllability (PFDR = .023) and decreased modal controllability (PFDR = .023) in dorsal anterior cingulate cortex (dACC). General psychopathology symptoms and positive symptoms were positively correlated with average controllability in regions of default mode network and negatively associated with average controllability in regions of sensorimotor, dorsal attention, and frontoparietal networks. CONCLUSIONS: Our findings suggest that altered controllability of functional activity in dACC may play a critical role in the pathophysiology of schizophrenia, consistent with the importance of this region in cognitive and brain state control operations. The demonstration of associations of functional controllability with psychosis symptoms suggests that the identified alterations in average controllability of brain function may contribute to the severity of acute psychotic illness in schizophrenia.