Cognition and motion dysfunction-associated brain functional network disruption in diabetic peripheral neuropathy.

Neuroimaging studies have demonstrated extensive brain functional alterations in cognitive and motor functional areas in Type 2 diabetes mellitus (T2DM) with diabetic peripheral neuropathy (DPN), suggesting potential alterations in large-scale brain networks related to DPN and associated cognition and motor dysfunction. In this study, using resting-state functional connectivity (FC) and graph theory computational approaches, we investigated the topological disruptions of brain functional networks in 28 DPN, 43 T2DM without DPN (NDPN), and 32 healthy controls (HCs) and examined the correlations between altered network topological metrics and cognitive/motor function parameters in T2DM. For global topology, NDPN exhibited a significantly decreased shortest path length compared with HCs, suggesting increased efficient global integration. For regional topology, DPN and NDPN had separated topological reorganization of functional hubs compared with HCs. In addition, DPN showed significantly decreased nodal efficiency (Enodal ), mainly in the bilateral superior occipital gyrus (SOG), right cuneus, middle temporal gyrus (MTG), and left inferior parietal gyrus (IPL), compared with NDPN, whereas NDPN showed significantly increased Enodal compared with HCs. Intriguingly, in T2DM patients, the Enodal of the right SOG was significantly negatively correlated with Toronto Clinical Scoring System scores, while the Enodal of the right postcentral gyrus (PoCG) and MTG were significantly positively correlated with Montreal Cognitive Assessment scores. Conclusively, DPN and NDPN patients had segregated disruptions in the brain functional network, which were related to cognition and motion dysfunctions. Our findings provide a theoretical basis for understanding the neurophysiological mechanism of DPN and its effective prevention and treatment in T2DM.

Specific Alterations in Brain White Matter Networks and Their Impact on Clinical Function in Pediatric Patients With Thoracolumbar Spinal Cord Injury.

BACKGROUND: The alternation of brain white matter (WM) network has been studied in adult spinal cord injury (SCI) patients. However, the WM network alterations in pediatric SCI patients remain unclear. PURPOSE: To evaluate WM network changes and their functional impact in children with thoracolumbar SCI (TSCI). STUDY TYPE: Prospective. SUBJECTS: Thirty-five pediatric patients with TSCI (8.94 ± 1.86 years, 8/27 males/females) and 34 age- and gender-matched healthy controls (HCs) participated in this study. FIELD STRENGTH/SEQUENCE: 3.0 T/DTI imaging using spin-echo echo-planar and T1-weighted imaging using 3D T1-weighted magnetization-prepared rapid gradient-echo sequence. ASSESSMENT: Pediatric SCI patients were evaluated for motor and sensory scores, injury level, time since injury, and age at injury. The WM network was constructed using a continuous tracing method, resulting in a 90 × 90 matrix. The global and regional metrics were obtained to investigate the alterations of the WM structural network. topology. STATISTICAL TESTS: Two-sample independent t-tests, chi-squared test, Mann-Whitney U-test, and Spearman correlation. Statistical significance was set at P < 0.05. RESULTS: Compared with HCs, pediatric TSCI patients displayed decreased shortest path length (Lp = 1.080 ± 0.130) and normalized Lp (λ = 5.020 ± 0.363), and increased global efficiency (Eg = 0.200 ± 0.015). Notably, these patients also demonstrated heightened regional properties in the orbitofrontal cortex, limbic system, default mode network, and several audio-visual-related regions. Moreover, the λ and Lp values negatively correlated with sensory scores. Conversely, nodal efficiency values in the right calcarine fissure and surrounding cortex positively correlated with sensory scores. The age at injury positively correlated with node degree in the left parahippocampal gyrus and nodal efficiency in the right posterior cingulate gyrus. DATA CONCLUSION: Reorganization of the WM networks in pediatric SCI patients is indicated by increased global and nodal efficiency, which may provide promising neuroimaging biomarkers for functional assessment of pediatric SCI. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 5.

The relationship between the structural changes in the cervical spinal cord and sensorimotor function of children with thoracolumbar spinal cord injury (TLSCI).

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To study the relationship between the structural changes in the cervical spinal cord (C2/3 level) and the sensorimotor function of children with traumatic thoracolumbar spinal cord injury (TLSCI) and to discover objective imaging biomarkers to evaluate its functional status. SETTING: Xuanwu Hospital, Capital Medical University, China; Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, China. METHODS: 30 children (age range 5-13 years) with TLSCI and 11 typically developing (TD) children (age range 6-12 years) were recruited in this study. Based on whether there is preserved motor function below the neurological level of injury (NLI), the children with TLSCI are divided into the AIS A/B group (motor complete) and the AIS C/D group (motor incomplete). A Siemens Verio 3.0 T MR scanner was used to acquire 3D high-resolution anatomic scans covering the head and upper cervical spinal cord. Morphologic parameters of the spinal cord at the C2/3 level, including cross-sectional area (CSA), anterior-posterior width (APW), and left-right width (LRW) were obtained using the spinal cord toolbox (SCT; https://www.nitrc.org/projects/sct ). Correlation analyses were performed to compare the morphologic spinal cord parameters and clinical scores determined by the International Standard for Neurological Classification of Spinal Cord Injuries (ISNCSCI) examination. RESULTS: CSA and LRW in the AIS A/B group were significantly lower than those in the TD group and the AIS C/D group. LRW was the most sensitive imaging biomarker to differentiate the AIS A/B group from the AIS C/D group. Both CSA and APW were positively correlated with ISNCSCI sensory scores. CONCLUSIONS: Quantitative measurement of the morphologic spinal cord parameters of the cervical spinal cord can be used as an objective imaging biomarker to evaluate the neurological function of children with TLSCI. Cervical spinal cord atrophy in children after TLSCI was correlated with clinical grading; CSA and APW can reflect sensory function. Meanwhile, LRW has the potential to be an objective imaging biomarker for evaluating motor function preservation.

Disrupted topological organization of resting-state functional brain networks in cerebral small vessel disease.

We aimed to investigate alterations in functional brain networks and assess the relationship between functional impairment and topological network changes in cerebral small vessel disease (CSVD) patients with and without cerebral microbleeds (CMBs). We constructed individual whole-brain, region of interest (ROI) level functional connectivity (FC) networks for 24 CSVD patients with CMBs (CSVD-c), 42 CSVD patients without CMBs (CSVD-n), and 36 healthy controls (HCs). Then, we used graph theory analysis to investigate the global and nodal topological disruptions between groups and relate network topological alterations to clinical parameters. We found that both the CSVD and control groups showed efficient small-world organization in FC networks. However, compared to CSVD-n patients and controls, CSVD-c patients exhibited a significantly decreased clustering coefficient, global efficiency, and local efficiency and an increased shortest path length, indicating a disrupted balance between local specialization and global integration in FC networks. Although both the CSVD and control groups showed highly similar hub distributions, the CSVD-c group exhibited significantly altered nodal betweenness centrality (BC), mainly distributed in the default mode network (DMN), attention, and visual functional areas. There were almost no global or regional alterations between CSVD-n patients and controls. Furthermore, the altered nodal BC of the right anterior/posterior cingulate gyrus and left cuneus were significantly correlated with cognitive parameters in CSVD patients. These results suggest that CSVD patients with and without CMBs had segregated disruptions in the topological organization of the intrinsic functional brain network. This study advances our current understanding of the pathophysiological mechanisms underlying CSVD.

Decreased Local Specialization of Brain Structural Networks Associated with Cognitive Dysfuntion Revealed by Probabilistic Diffusion Tractography for Different Cerebral Small Vessel Disease Burdens.

To reveal the network-level structural disruptions associated with cognitive dysfunctions in different cerebral small vessel disease (CSVD) burdens, we used probabilistic diffusion tractography and graph theory to investigate the brain network topology in 67 patients with a severe CSVD burden (CSVD-s), 133 patients with a mild CSVD burden (CSVD-m) and 89 healthy controls. We used one-way analysis of covariance to assess the altered topological measures between groups, and then evaluated their Pearson correlation with cognitive parameters. Both the CSVD and control groups showed efficient small-world organization in white matter (WM) networks. However, compared with CSVD-m patients and controls, CSVD-s patients exhibited significantly decreased local efficiency, with partially reorganized hub distributions. For regional topology, CSVD-s patients showed significantly decreased nodal efficiency in the bilateral anterior cingulate gyrus, caudate nucleus, right opercular inferior frontal gyrus (IFGoperc), supplementary motor area (SMA), insula and left orbital superior frontal gyrus and angular gyrus. Intriguingly, global/local efficiency and nodal efficiency of the bilateral caudate nucleus, right IFGoperc, SMA and left angular gyrus showed significant correlations with cognitive parameters in the CSVD-s group, while only the left pallidum showed significant correlations with cognitive metrics in the CSVD-m group. In conclusion, the decreased local specialization of brain structural networks in patients with different CSVD burdens provides novel insights into understanding the brain structural alterations in relation to CSVD severity. Cognitive correlations with brain structural network efficiency suggest their potential use as neuroimaging biomarkers to assess the severity of CSVD.

A fluorescent probe for detecting bisulfite/sulfite in lipid droplets and tracking the dynamics of lipid droplets.

Intracellular lipid droplets (LDs) are important organelles regulating intracellular redox processes. Endogenous bisulfite/sulfite (HSO3-/SO32-) is one of the metabolites of thiol metabolism. The variation in HSO3-/SO32- content around LDs is closely related to cellular homeostasis. However, there is currently no effective method to visualize and quantify the dynamic changes in HSO3-/SO32- content around LDs. In this work, a fluorescent probe MC-BEN utilizing a triphenylamine basic framework was developed to selectively recognize HSO3-/SO32- via a nucleophilic addition reaction. The probe exhibits excellent anti-interference capability, short response time, outstanding photostability, and a low fluorescence detection limit (6.1 µM) for HSO3-/SO32- recognition. More interesting, there is a trend of accelerated contact between LDs and lysosomes after MC-BEN targeting LDs and reacting with endogenous/exogenous HSO3-/SO32-, which may provide new ideas for the study of intracellular lysosomal lipophagy.

Aberrant brain structural-functional connectivity coupling associated with cognitive dysfunction in different cerebral small vessel disease burdens.

AIMS: Emerging evidence suggests that cerebral small vessel disease (CSVD) pathology changes brain structural connectivity (SC) and functional connectivity (FC) networks. Although network-level SC and FC are closely coupled in the healthy population, how SC-FC coupling correlates with neurocognitive outcomes in patients with different CSVD burdens remains largely unknown. METHODS: Using multimodal MRI, we reconstructed whole-brain SC and FC networks for 54 patients with severe CSVD burden (CSVD-s), 106 patients with mild CSVD burden (CSVD-m), and 79 healthy controls. We then investigated the aberrant SC-FC coupling and functional network topology in CSVD and their correlations with cognitive dysfunction. RESULTS: Compared with controls, the CSVD-m patients showed no significant change in any SC-FC coupling, but the CSVD-s patients exhibited significantly decreased whole-brain (p = 0.014), auditory/motor (p = 0.033), and limbic modular (p = 0.011) SC-FC coupling. For functional network topology, despite no change in global efficiency, CSVD-s patients exhibited significantly reduced nodal efficiency of the bilateral amygdala (p = 0.024 and 0.035) and heschl gyrus (p = 0.001 and 0.005). Notably, for the CSVD-s patients, whole-brain SC-FC coupling showed a significantly positive correlation with MoCA (r = 0.327, p = 0.020) and SDMT (r = 0.373, p = 0.008) scores, limbic/subcortical modular SC-FC coupling showed a negative correlation (r = -0.316, p = 0.025) with SCWT score, and global/local efficiency (r = 0.367, p = 0.009 and r = 0.353, p = 0.012) showed a positive correlation with AVLT score. For the CSVD-m group, whole-brain and auditory/motor modular SC-FC couplings showed significantly positive correlations with SCWT (r = 0.217, p = 0.028 and r = 0.219, p = 0.027) and TMT (r = 0.324, p = 0.001 and r = 0.245, p = 0.013) scores, and global/local efficiency showed positive correlations with AVLT (r = 0.230, p = 0.020 and r = 0.248, p = 0.012) and SDMT (r = 0.263, p = 0.008 and r = 0.263, p = 0.007) scores. CONCLUSION: Our findings demonstrated that decreased whole-brain and module-dependent SC-FC coupling associated with reduced functional efficiency might underlie more severe burden and worse cognitive decline in CSVD. SC-FC coupling might serve as a more sensitive neuroimaging biomarker of CSVD burden and provided new insights into the pathophysiologic mechanisms of clinical development of CSVD.

Coumarin-aurone based fluorescence probes for cysteine sensitive in-situ identification in living cells.

The quantification of cysteine (Cys) levels in the organisms holds paramount significance in biological research and disease diagnosis, which can give the correlation between abnormal Cys levels and diseases. In this study, two fluorescent probes, designated as DEA-OH and DEA-AC, featuring a coumarin-aurone backbone specifically engineered for Cys detection, were meticulously designed and synthesized. The diethylamino coumarin-aurone probe DEA-OH and the acrylate-substituted probe DEA-AC demonstrated remarkable sensitivity in detecting cysteine by means of copper displacement (DEA-OH) and acrylate hydrolysis mechanisms (DEA-AC) with fluorescence detection limits of 7.25 µM and 1.65 µM, respectively. Moreover, the fluorescence peak wavelength of the two probes displayed a linear relationship with solvent polarity in the ET (30) range of 30-65 kcal•mol-1, indicating the potential for monitoring changes in environmental polarity within this ET (30) range. The outstanding attributes exhibited by DEA-AC including superior photostability, remarkable selectivity, and swift response (kinetic rate constant: 0.00747 s-1), coupled with the exceptional anti-interference ability, have significantly broadened its scope of applications, for example detecting alterations in Cys within biological systems.

Near-infrared and multifunctional fluorescent probe enabled by cyanopyridine cyanine dye for bisulfite recognition and biological imaging.

SO2 derivatives, sulfite/bisulfite, are widely employed in both the food processing and drug synthesis industries. Despite their widespread application, excessive levels of sulfite/bisulfite can negatively impact human health. Most probes for detecting sulfite/bisulfite are restricted by their fluorescence within the visible spectrum range and poor solubility in aqueous solution, which limit their use in food testing and biological imaging. Herein, a near-infrared probe comprising of the cyanopyridine cyanine skeleton, 4-((Z)-2-((E)-2-chloro-3-(2-cyano-2-(1-methylpyridine-4(1H)-ylidene)ethylidene)cyclohex-1-en-1-yl)-1-cyanovinyl)-1-methylpyridin-1-ium (abbreviated as CCP), was developed. This probe enables precise quantification of bisulfite (HSO3-) in almost pure buffered solutions, showing a near-infrared fluorescence emission at 784 nm with an impressively low detection limit of 0.32 µM. The probe stands out for its exceptional selectivity, minimal susceptibility to interference, and strong adaptability. The probe CCP utilizes the CC bond to trigger a near-infrared fluorescence quenching reaction with HSO3- via nucleophilic addition, which effectively disrupts the large delocalization within the molecule for accurate HSO3- identification. Moreover, the probe has been successfully applied in detecting HSO3- in various food products and living cells, simplifying the measurement of HSO3- content in water samples. This advancement not only enhances the analytical capabilities but also contributes to ensuring food safety and environmental protection. ENVIRONMENTAL IMPLICATION: SO2 derivatives including sulfite/bisulfite, serving dual roles as preservatives and antioxidants, have widespread application across various sectors including food preservation, water sanitation, and the pharmaceutical industry. Despite their widespread application, excessive levels of sulfite/bisulfite can affect human health. Developing methods for precisely and sensitively detecting sulfite/bisulfite in food products and biological samples is important for ensuring food safety and environmental protection. Here, a sensitive near-infrared and multifunctional fluorescent probe in a 99.9 % buffered solution, along with water gel encapsulation, has been successfully applied for the detection of bisulfite in food, authentic water samples, and biological cells.

Graph Metrics Reveal Brain Network Topological Property in Neuropathic Pain Patients: A Systematic Review.

Neuropathic pain (NP) is a common and persistent disease that leads to immense suffering and serious social burden. Incomplete understanding of the underlying neural basis makes it difficult to achieve significant breakthroughs in the treatment of NP. We aimed to review the functional and structural brain topological properties in patients with NP and consider how graph measures reveal potential mechanisms and are applied to clinical practice. Related studies were searched in PubMed and Web of Science databases. Topological property changes in patients with NP, including small-worldness, functional separation, integration, and centrality metrics, were reviewed. The findings suggest that NP was characterized by retained but declined small-worldness, indicating an insidious imbalance between network integration and segregation. The global-level measures revealed decreased global and local efficiency in the NP, implying decreased information transfer efficiency for both long- and short-range connections. Altered nodal centrality measures involve various brain regions, mostly those associated with pain, cognition, and emotion. Graph theory is a powerful tool for identifying topological properties of patients with NP. These specific brain changes in patients with NP are very helpful in revealing the potential mechanisms of NP, developing new treatment strategies, and evaluating the efficacy and prognosis of NP.

Disrupted brain structural networks associated with depression and cognitive dysfunction in cerebral small vessel disease with microbleeds.

Emerging evidence highlights cerebral microbleeds (CMBs) as hallmarks of cerebral small vessel disease (CSVD) underlying depression and cognitive dysfunction. This study aimed to reveal how depression and cognition-related white matter (WM) abnormalities are topologically presented, and the network-level structural disruptions associated with CMBs in CSVD. We used probabilistic diffusion tractography and graph theory to investigate brain WM network topology in CSVD patients with (n = 64, CSVD-c) and without (n = 138, CSVD-n) CMBs and 90 healthy controls. Then we evaluated the Pearson's correlations between disrupted network metrics and neuropsychological parameters. For global topology, the CSVD-c group exhibited significantly decreased global (Eglob) and local (Eloc) efficiency and increased shortest path length compared with the controls, while no significant difference was found between the CSVD-c and CSVD-n groups. For regional topology, although all groups showed highly similar hub distributions, compare with control group, the CSVD-c group exhibited significantly decreased nodal efficiency mainly in the bilateral supplementary motor area (SMA), median cingulate gyrus (DCG) and right orbital middle frontal gyrus, while the CSVD-n group showed significantly decreased nodal efficiency only in the right SMA. Notably, Eglob, Eloc and nodal efficiency of the right anterior cingulate gyrus, DCG, middle temporal gyrus and left insula showed significantly negative correlations with depression score, significantly positive correlations with Rey auditory verbal learning test and symbol digit modalities test scores in CSVD-n group, as well as significantly negative correlations with Stroop color-word test scores in CSVD-c group. The WM networks of CSVD patients are characterized by decreased global integration and local specialization, and decreased nodal efficiency highly related to depression and cognitive dysfunction in the attention, default mode network and sensorimotor regions. These findings provide new insight into the neurobiological mechanisms of CSVD and concomitant affective and cognitive disorders.

Distinct brain network patterns in complete and incomplete spinal cord injury patients based on graph theory analysis.

AIMS: To compare the changes in brain network topological properties and structure-function coupling in patients with complete spinal cord injury (CSCI) and incomplete spinal cord injury (ICSCI), to unveil the potential neurobiological mechanisms underlying the different effects of CSCI and ICSCI on brain networks and identify objective neurobiological markers to differentiate between CSCI and ICSCI patients. METHODS: Thirty-five SCI patients (20 CSCI and 15 ICSCI) and 32 healthy controls (HCs) were included in the study. Here, networks were constructed using resting-state functional magnetic resonance imaging to analyze functional connectivity (FC) and diffusion tensor imaging for structural connectivity (SC). Then, graph theory analysis was used to examine SC and FC networks, as well as to estimate SC-FC coupling values. RESULTS: Compared with HCs, CSCI patients showed increased path length (Lp), decreased global efficiency (Eg), and local efficiency (Eloc) in SC. For FC, ICSCI patients exhibited increased small-worldness, clustering coefficient (Cp), normalized clustering coefficient, and Eloc. Also, ICSCI patients showed increased Cp and Eloc than CSCI patients. Additionally, ICSCI patients had reduced SC-FC coupling values compared to HCs. Moreover, in CSCI patients, the SC network's Lp and Eg values were significantly correlated with motor scores, while in ICSCI patients, the FC network's Cp, Eloc, and SC-FC coupling values were related to sensory/motor scores. CONCLUSIONS: These results suggest that CSCI patients are characterized by decreased efficiency in the SC network, while ICSCI patients are distinguished by increased local connections and SC-FC decoupling. Moreover, the differences in network metrics between CSCI and ICSCI patients could serve as objective biological markers, providing a basis for diagnosis and treatment strategies.

Abnormal whole-brain voxelwise structure-function coupling and its association with cognitive dysfunction in patients with different cerebral small vessel disease burdens.

Cerebral small vessel disease (CSVD) is a universal neurological disorder in older adults that occurs in connection with cognitive dysfunction and is a chief risk factor for dementia and stroke. While whole-brain voxelwise structural and functional abnormalities in CSVD have been heavily explored, the degree of structure-function coupling abnormality possible in patients with different CSVD burdens remains largely unknown. This study included 53 patients with severe CSVD burden (CSVD-s), 108 patients with mild CSVD burden (CSVD-m) and 76 healthy controls. A voxelwise coupling metric of low frequency fluctuations (ALFF) and voxel-based morphometry (VBM) was used to research the important differences in whole-brain structure-function coupling among groups. The correlations between ALFF/VBM decoupling and cognitive parameters in CSVD patients were then investigated. We found that compared with healthy controls, CSVD-s patients presented notably decreased ALFF/VBM coupling in the bilateral caudate nuclei and increased coupling in the right inferior temporal gyrus (ITG). In addition, compared with the CSVD-m group, the CSVD-s group demonstrated significantly decreased coupling in the bilateral caudate nuclei, right putamen and inferior frontal gyrus (IFG) and increased coupling in the left middle frontal gyrus and medial superior frontal gyrus. Notably, the ALFF/VBM decoupling values in the caudate, IFG and ITG not only showed significant correlations with attention and executive functions in CSVD patients but also prominently distinguished CSVD-s patients from CSVD-m patients and healthy controls in receiver operating characteristic curve research. Our discoveries demonstrated that decreased ALFF/VBM coupling in the basal ganglia and increased coupling in the frontotemporal lobes were connected with more severe burden and worse cognitive decline in CSVD patients. ALFF/VBM coupling might serve as a novel effective neuroimaging biomarker of CSVD burden and provide new insights into the pathophysiological mechanisms of the clinical development of CSVD.

Characterization of white matter microstructural abnormalities associated with cognitive dysfunction in cerebral small vessel disease with cerebral microbleeds.

BACKGROUND: Diffusion tensor imaging (DTI) is recommended as a sensitive method to explore white matter (WM) microstructural alterations. Cerebral small vessel disease (CSVD) may be accompanied by extensive WM microstructural deterioration, while cerebral microbleeds (CMBs) are an important factor affecting CSVD. METHODS: Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 49 CSVD patients with CMBs (CSVD-c), 114 CSVD patients without CMBs (CSVD-n), and 83 controls were analyzed using DTI-derived tract-based spatial statistics to detect WM diffusion changes among groups. RESULTS: Compared with the CSVD-n and control groups, the CSVD-c group showed a significant FA decrease and AD, RD and MD increases mainly in the cognitive and sensorimotor-related WM tracts. There was no significant difference in any diffusion metric between the CSVD-n and control groups. Furthermore, the widespread regional diffusion alterations among groups were significantly correlated with cognitive parameters in both the CSVD-c and CSVD-n groups. Notably, we applied the multiple kernel learning technique in multivariate pattern analysis to combine multiregion and multiparameter diffusion features, yielding an average accuracy >77 % for three binary classifications, which showed a considerable improvement over the single modality approach. LIMITATIONS: We only grouped the study according to the presence or absence of CMBs. CONCLUSIONS: CSVD patients with CMBs have extensive WM microstructural deterioration. Combining DTI-derived diffusivity and anisotropy metrics can provide complementary information for assessing WM alterations associated with cognitive dysfunction and serve as a potential discriminative pattern to detect CSVD at the individual level.

Diagnosis of cervical lymph node metastasis with thyroid carcinoma by deep learning application to CT images.

Introduction: The incidence of thyroid diseases has increased in recent years, and cervical lymph node metastasis (LNM) is considered an important risk factor for locoregional recurrence. This study aims to develop a deep learning-based computer-aided diagnosis (CAD) method to diagnose cervical LNM with thyroid carcinoma on computed tomography (CT) images. Methods: A new deep learning framework guided by the analysis of CT data for automated detection and classification of LNs on CT images is proposed. The presented CAD system consists of two stages. First, an improved region-based detection network is designed to learn pyramidal features for detecting small nodes at different feature scales. The region proposals are constrained by the prior knowledge of the size and shape distributions of real nodes. Then, a residual network with an attention module is proposed to perform the classification of LNs. The attention module helps to classify LNs in the fine-grained domain, improving the whole classification network performance. Results: A total of 574 axial CT images (including 676 lymph nodes: 103 benign and 573 malignant lymph nodes) were retrieved from 196 patients who underwent CT for surgical planning. For detection, the data set was randomly subdivided into a training set (70%) and a testing set (30%), where each CT image was expanded to 20 images by rotation, mirror image, changing brightness, and Gaussian noise. The extended data set included 11,480 CT images. The proposed detection method outperformed three other detection architectures (average precision of 80.3%). For classification, ROI of lymph node metastasis labeled by radiologists were used to train the classification network. The 676 lymph nodes were randomly divided into 70% of the training set (73 benign and 401 malignant lymph nodes) and 30% of the test set (30 benign and 172 malignant lymph nodes). The classification method showed superior performance over other state-of-the-art methods with an accuracy of 96%, true positive and negative rates of 98.8 and 80%, respectively. It outperformed radiologists with an area under the curve of 0.894. Discussion: The extensive experiments verify the high efficiency of the proposed method. It is considered instrumental in a clinical setting to diagnose cervical LNM with thyroid carcinoma using preoperative CT images. The future research can consider adding radiologists' experience and domain knowledge into the deep-learning based CAD method to make it more clinically significant. Conclusion: The extensive experiments verify the high efficiency of the proposed method. It is considered instrumental in a clinical setting to diagnose cervical LNM with thyroid carcinoma using preoperative CT images.

Voxel-based morphometry reveals the correlation between gray matter volume and serum P-tau-181 in type 2 diabetes mellitus patients with different HbA1c levels.

Introduction: Emerging evidence suggested widespread decreased gray matter volume (GMV) and tau hyperphosphorylation were associated with type 2 diabetes mellitus (T2DM). Insulin resistance is one of the mechanisms of neuron degeneration in T2DM; it can decrease the activity of protein kinase B and increase the activity of glycogen synthesis kinase-3ß, thus promoting the hyperphosphorylation of tau protein and finally leading to neuronal degeneration. However, the association between GMV and serum tau protein phosphorylated at threonine 181 (P-tau-181) in T2DM patients lacks neuroimaging evidence. We aimed to investigate the difference in brain GMV between T2DM patients with different glycated hemoglobin A1c (HbA1c) levels and healthy control (HC) subjects and the correlation between serum P-tau-181 and GMV in T2DM patients. Methods: Clinical parameters, biochemical indicators, and MRI data were collected for 41 T2DM patients with high glycosylated hemoglobin level (HGL), 17 T2DM patients with normal glycosylated hemoglobin level (NGL), and 42 HC subjects. Voxel-based morphometry (VBM) method was applied to investigate GMV differences among groups, and multiple regression analysis was used to examine the correlation between serum P-tau-181 and GMV. Results: Compared with HC subjects, the T2DM patients with HGL or NGL all showed significantly decreased GMV. Briefly, the GMV decreased in T2DM patients with HGL was mainly in the bilateral parahippocampal gyrus (PHG), right middle temporal gyrus (MTG), temporal pole (TPOmid), hippocampus (HIP), and left lingual gyrus. The GMV reduction in T2DM patients with NGL was in the right superior temporal gyrus (STG), and there was no significant difference in GMV between the two diabetic groups. The GMV values of bilateral PHG, right MTG, TPOmid, HIP, and STG can significantly (p < 0.0001) distinguish T2DM patients from HC subjects in ROC curve analysis. In addition, we found that serum P-tau-181 levels were positively correlated with GMV in the right superior and middle occipital gyrus and cuneus, and negatively correlated with GMV in the right inferior temporal gyrus in T2DM patients. Conclusion: Our study shows that GMV atrophy can be used as a potential biological indicator of T2DM and also emphasizes the important role of P-tau-181 in diabetic brain injury, providing new insights into the neuropathological mechanism of diabetic encephalopathy.

Disrupted Gray Matter Networks Associated with Cognitive Dysfunction in Cerebral Small Vessel Disease.

This study aims to investigate the disrupted topological organization of gray matter (GM) structural networks in cerebral small vessel disease (CSVD) patients with cerebral microbleeds (CMBs). Subject-wise structural networks were constructed from GM volumetric features of 49 CSVD patients with CMBs (CSVD-c), 121 CSVD patients without CMBs (CSVD-n), and 74 healthy controls. The study used graph theory to analyze the global and regional properties of the network and their correlation with cognitive performance. We found that both the control and CSVD groups exhibited efficient small-world organization in GM networks. However, compared to controls, CSVD-c and CSVD-n patients exhibited increased global and local efficiency (Eglob/Eloc) and decreased shortest path lengths (Lp), indicating increased global integration and local specialization in structural networks. Although there was no significant global topology change, partially reorganized hub distributions were found between CSVD-c and CSVD-n patients. Importantly, regional topology in nonhub regions was significantly altered between CSVD-c and CSVD-n patients, including the bilateral anterior cingulate gyrus, left superior parietal gyrus, dorsolateral superior frontal gyrus, and right MTG, which are involved in the default mode network (DMN) and sensorimotor functional modules. Intriguingly, the global metrics (Eglob, Eloc, and Lp) were significantly correlated with MoCA, AVLT, and SCWT scores in the control group but not in the CSVD-c and CSVD-n groups. In contrast, the global metrics were significantly correlated with the SDMT score in the CSVD-s and CSVD-n groups but not in the control group. Patients with CSVD show a disrupted balance between local specialization and global integration in their GM structural networks. The altered regional topology between CSVD-c and CSVD-n patients may be due to different etiological contributions, which may offer a novel understanding of the neurobiological processes involved in CSVD with CMBs.

A two-photon iridium(III) complex probe for sensitive detection of SO2 derivatives in living cell mitochondria.

The derivatives of sulfur dioxide (HSO3-) formed in the biological environment play a vital role in the circulation system. Excessive SO2 derivatives will cause serious damage to the living system. Herein, a two-photon phosphorescent probe based on Ir(III) complex (named as Ir-CN) was designed and synthesized. Ir-CN is extremely selective and sensitive to SO2 derivatives with significant phosphorescent enhancement and increased phosphorescent lifetime. The detection limit of Ir-CN for SO2 derivatives reaches 0.17 µM. More importantly, Ir-CN preferentially accumulates in mitochondria, so bisulfite derivatives can be detected at subcellular level, which enriching the application of metal complex probe in biological detection. In addition, both single-photon and two-photon images can clearly show that Ir-CN is targeted to mitochondria. Benefits from its good biocompatibility, Ir-CN may be used as a reliable tool to detect SO2 derivatives in mitochondrion of living cells.

Altered Intrinsic Brain Activity Related to Neurologic and Motor Dysfunction in Diabetic Peripheral Neuropathy Patients.

CONTEXT: Brain functional alterations in type 2 diabetes with diabetic peripheral neuropathy (DPN) related to motor dysfunction remain largely unknown. OBJECTIVE: We aimed to explore intrinsic resting brain activity in DPN. METHODS: A total of 28 patients with DPN, 43 patients with diabetes and without DPN (NDPN), and 32 healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging. We calculated the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo). One-way analysis of covariance was applied to evaluate the above indicators among the 3 groups, and the mean ALFF/fALFF/ReHo values of altered brain regions were then correlated with clinical features of patients. RESULTS: Compared with the NDPN group, the DPN group showed significantly decreased ALFF values in the right orbital superior frontal gyrus (ORBsup) and medial superior frontal gyrus (SFGmed), and increased ALFF values in the left inferior temporal gyrus (ITG) and decreased fALFF values in the right SFGmed. Compared with HCs, the NDPN group showed increased ALFF values in the right ORBsup, middle frontal gyrus, and left orbital middle frontal gyrus, and decreased fALFF values in the right middle temporal gyrus. Notably, the mean ALFF values of the right ORBsup were significantly negatively correlated with Toronto Clinical Scoring System scores and gait speed in diabetics. The mean ALFF/fALFF values of right SFGmed and the mean ALFF values of left ITG and right ORBsup were significantly differentiated between DPN and patients witht NDPN in receiver operating characteristic curve analysis. CONCLUSION: Patients with DPN have abnormal brain activity in sensorimotor and cognitive brain areas, which may implicate the underlying neurophysiological mechanisms in intrinsic brain activity.

Altered Spontaneous Brain Activity Related to Neurologic Dysfunction in Patients With Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) encompasses several diseases affecting the small arteries, arterioles, venules, and capillaries of the brain and refers to several pathological processes and etiologies. Neuroimaging is considered the gold standard for detecting CSVD, which can present diverse features on MRI. Cerebral microbleeds (CMBs) in CSVD have been demonstrated to play a synergistic role in both cerebrovascular and neurodegenerative pathology. Considering previous studies on brain structural abnormalities in CSVD, in the present study, we aimed to explore altered spontaneous brain activity among CSVD patients using amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and regional homogeneity (ReHo) methods based on resting-state functional MRI. In this study, we recruited 24 CSVD patients with CMBs (CSVD-c), 42 CSVD patients without CMBs (CSVD-n) and 36 healthy controls from outpatient clinics in Shandong Provincial Hospital affiliated to Shandong First Medical University between September 2018 and June 2019. All subjects underwent 3-T MRI, including blood oxygen level-dependent (BOLD) and susceptibility-weighted imaging (SWI). Anatomic structures were segmented, ALFF/fALFF values were calculated, and ReHo maps were generated. Further statistical analysis was applied to study the difference in ALFF/fALFF/ReHo among the three groups and the association between ALFF/fALFF/ReHo changes in different brain regions and clinical characteristics. Twenty-four CSVD-c patients (age: 67.54 ± 6.00 years, 10 females), 42 CSVD-n patients (age: 66.33 ± 5.25 years, 22 females) and 36 healthy subjects (age: 64.14 ± 8.57 years, 19 females) were evaluated. Compared with controls, the CSVD-c group showed significantly increased ALFF values in the right insula, putamen and left precuneus; decreased fALFF values in the right precentral gyrus and postcentral gyrus; and increased ReHo values in the left precuneus, fusiform gyrus, right supplementary motor area (SMA), and superior frontal gyrus. Notably, the mean ALFF values of the right insula and putamen were not only significantly related to all clinical parameters but also demonstrated the best performance in Receiver Operating Characteristic (ROC) curve analysis. These findings reveal CSVD-c patients have dysfunctions in the default mode network, sensorimotor network and frontoparietal network, which may implicate the underlying neurophysiological mechanisms of intrinsic brain activity. The correlation between altered spontaneous neuronal activity and clinical parameters provides early useful diagnostic biomarkers for CSVD.