Value of turbo spin echo-based diffusion-weighted imaging in the differential diagnosis of benign and malignant solitary pulmonary lesions.

To quantitatively assess the diagnostic efficacy of multiple parameters derived from multi-b-value diffusion-weighted imaging (DWI) using turbo spin echo (TSE)-based acquisition techniques in patients with solitary pulmonary lesions (SPLs). A total of 105 patients with SPLs underwent lung DWI using single-shot TSE-based acquisition techniques and multiple b values. The apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) parameters, and lesion-to-spinal cord signal intensity ratio (LSR), were analyzed to compare the benign and malignant groups using the Mann-Whitney U test and receiver operating characteristic analysis. The Dstar values observed in lung cancer were slightly lower than those observed in pulmonary benign lesions (28.164 ± 31.950 versus 32.917 ± 34.184; Z = -2.239, p = 0.025). The LSR values were significantly higher in lung cancer than in benign lesions (1.137 ± 0.581 versus 0.614 ± 0.442; Z = - 4.522, p < 0.001). Additionally, the ADC800, ADCtotal, and D values were all significantly lower in lung cancer than in the benign lesions (Z = - 5.054, -5.370, and -6.047, respectively, all p < 0.001), whereas the f values did not exhibit any statistically significant difference between the two groups. D had the highest area under the curve (AUC = 0.887), followed by ADCtotal (AUC = 0.844), ADC800 (AUC = 0.824), and LSR (AUC = 0.789). The LSR, ADC800, ADCtotal, and D values did not differ statistically significantly in diagnostic effectiveness. Lung DWI using TSE is feasible for differentiating SPLs. The LSR method, conventional DWI, and IVIM have comparable diagnostic efficacy for assessing SPLs.

Bipolar Patient-Specific In Vitro Diagnostic Test Reveals Underlying Cardiac Arrhythmia Phenotype Caused by Calcium Channel Genetic Risk Factor.

A common genetic risk factor for bipolar disorder is CACNA1C, a gene that is also critical for cardiac rhythm. The impact of CACNA1C mutations on bipolar patient cardiac rhythm is unknown. Here, we report the cardiac electrophysiological implications of a bipolar disorder-associated genetic risk factor in CACNA1C using patient induced pluripotent stem cell-derived cardiomyocytes. Results indicate that the CACNA1C bipolar disorder-related mutation causes cardiac electrical impulse conduction slowing mediated by impaired intercellular coupling via connexin 43 gap junctions. In vitro gene therapy to restore connexin 43 expression increased cardiac electrical impulse conduction velocity and protected against thioridazine-induced QT prolongation. Patients positive for bipolar disorder CACNA1C genetic risk factors may have elevated proarrhythmic risk for adverse events in response to psychiatric medications that slow conduction or prolong the QT interval. This in vitro diagnostic tool enables cardiac testing specific to patients with psychiatric disorders to determine their sensitivity to off-target effects of psychiatric medications.

Bipolar disorder (BD) is associated with genetic risk factors that present as mutations in specific genes. One gene commonly associated with BD is the calcium channel gene CACNA1C, found in the brain and the heart. The impact of CACNA1C mutation on cardiac function in patients with BD is unclear. Here, we created a BD CACNA1C mutant patient "heart in a dish" using patient-specific stem cells. Gene editing was also used to correct the mutation to create an isogenic control cell line. We found that the BD calcium gene mutation caused slow electrical impulse propagation, reduced the function of the calcium channel, and was associated with low intercellular communication channels called connexin. Using connexin gene therapy in vitro, the the cardiac dysfunction could be corrected and cured. This new approach offers patient-specific hearts-in-a-dish that can be used to ensure that medications will not cause heart racing or arrhythmias.

Cortical-cerebellar circuits changes in preschool ASD children by multimodal MRI.

OBJECTIVE: To investigate the alterations in cortical-cerebellar circuits and assess their diagnostic potential in preschool children with autism spectrum disorder using multimodal magnetic resonance imaging. METHODS: We utilized diffusion basis spectrum imaging approaches, namely DBSI_20 and DBSI_combine, alongside 3D structural imaging to examine 31 autism spectrum disorder diagnosed patients and 30 healthy controls. The participants' brains were segmented into 120 anatomical regions for this analysis, and a multimodal strategy was adopted to assess the brain networks using a multi-kernel support vector machine for classification. RESULTS: The results revealed consensus connections in the cortical-cerebellar and subcortical-cerebellar circuits, notably in the thalamus and basal ganglia. These connections were predominantly positive in the frontoparietal and subcortical pathways, whereas negative consensus connections were mainly observed in frontotemporal and subcortical pathways. Among the models tested, DBSI_20 showed the highest accuracy rate of 86.88%. In addition, further analysis indicated that combining the 3 models resulted in the most effective performance. CONCLUSION: The connectivity network analysis of the multimodal brain data identified significant abnormalities in the cortical-cerebellar circuits in autism spectrum disorder patients. The DBSI_20 model not only provided the highest accuracy but also demonstrated efficiency, suggesting its potential for clinical application in autism spectrum disorder diagnosis.

Bionic nanotheranostic for multimodal imaging-guided NIR-II-photothermal cancer therapy.

In photothermal therapy (PTT), the photothermal conversion of the second near-infrared (NIR-II) window allows deeper penetration and higher laser irradiance and is considered a promising therapeutic strategy for deep tissues. Since cancer remains a leading cause of deaths worldwide, despite the numerous treatment options, we aimed to develop an improved bionic nanotheranostic for combined imaging and photothermal cancer therapy. We combined a gold nanobipyramid (Au NBP) as a photothermal agent and MnO2 as a magnetic resonance enhancer to produce core/shell structures (Au@MnO2; AM) and modified their surfaces with homologous cancer cell plasma membranes (PM) to enable tumour targeting. The performance of the resulting Au@MnO2@PM (AMP) nanotheranostic was evaluated in vitro and in vivo. AMP exhibits photothermal properties under NIR-II laser irradiation and has multimodal in vitro imaging functions. AMP enables the computed tomography (CT), photothermal imaging (PTI), and magnetic resonance imaging (MRI) of tumours. In particular, AMP exhibited a remarkable PTT effect on cancer cells in vitro and inhibited tumour cell growth under 1064 nm laser irradiation in vivo, with no significant systemic toxicity. This study achieved tumour therapy guided by multimodal imaging, thereby demonstrating a novel strategy for the use of bionic gold nanoparticles for tumour PTT under NIR-II laser irradiation.

Alterations in functional connectivity in patients with non-specific chronic low back pain after motor control exercise: a randomized trial.

BACKGROUND: Motor control exercise (MCE) is effective in alleviating non-specific chronic low back pain (NCLBP). Neuro-imaging research is warranted to explore the underlying neural mechanisms of MCE. AIM: We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the central mechanism underpinning the effects of MCE in patients with NCLBP. DESIGN: A randomized, single-blinded, controlled trial. SETTING: The setting was out-patient and community. POPULATION: Fifty-eight patients with NCLBP. METHODS: Patients were randomized into the MCE or manual therapy (MT) group. All the participants completed pain-related clinical assessments and rs-fMRI scans before and after intervention. We performed exploratory whole-brain analyses in regional homogeneity (ReHo) and resting-state functional connectivity (rsFC) with significant post-pre differences in ReHo before and after intervention, and investigated associations between imaging and pain-related clinical assessments. RESULTS: Compared with the MT group, a greater alleviation in pain intensity and disability was observed in the MCE group after intervention, and was sustained at the 6-month follow-up (P<0.001). Only the MCE group showed increased ReHo values in the right pre-central gyrus and decreased ReHo values in the bilateral posterior cerebellum (voxel level P<0.001, cluster-level FWE corrected P<0.05). Decreased rsFC of the right posterior cerebellum-left superior parietal gyrus and left insula were significantly positively associated with pain-related disability (voxel level P<0.001, cluster-level FWE corrected P<0.05). CONCLUSIONS: These findings demonstrated that MCE had superior effects in relieving pain and pain-related disability, which might be associated with its modulation of rsFC between the cerebellum and areas involved in sensory-discriminative processing of noxious and somato-sensory stimuli, affection, and cognition. CLINICAL REHABILITATION IMPACT: This study provided preliminary evidence that MCE might alleviate NCLBP through its modulation of the function of brain areas related to chronic pain and postural control. Those results support MCE's clinical application and help physiotherapists to provide better multidisciplinary interventions with the combination of MCE and other first-line treatments.

Functional connectivity changes of the hippocampal subregions in anti-N-methyl-D-aspartate receptor encephalitis.

The hippocampus plays an important role in the pathophysiological mechanism of Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Nevertheless, the connection between the resting-state activity of the hippocampal subregions and neuropsychiatric disorders in patients remains unclear. This study aimed to explore the changes in functional connectivity (FC) in the hippocampal subregions of patients with anti-NMDAR encephalitis and its association with clinical symptoms and cognitive performance. Twenty-three patients with anti-NMDAR encephalitis and 23 healthy controls (HC) were recruited. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans and completed clinical cognitive scales. Based on the Brainnetome Atlas, the rostral (anterior) and caudal (posterior) hippocampi of both the left and right hemispheres were selected as regions of interest (ROIs) for FC analysis. First, a one-sample t-test was used to observe the whole-brain connectivity distribution of hippocampal subregions within the patient and HC groups at a threshold of p < 0.05. The two-sample t-test was used to compare the differences in hippocampal ROIs connectivity between groups, followed by a partial correlation analysis between the FC values of brain regions with statistical differences and clinical variables. This study observed that the distribution of whole-brain functional connectivity in the rostral and caudal hippocampi aligned with the connectivity differences between the anterior and posterior hippocampi. Compared to the HC group, the patients showed significantly decreased FC between the bilateral rostral hippocampus and the left inferior orbitofrontal gyrus and between the right rostral hippocampus and the right cerebellum. However, a significant increase in FC was observed between the right rostral hippocampus and left superior temporal gyrus, the left caudal hippocampus and right superior frontal gyrus, and the right caudal hippocampus and left gyrus rectus. Partial correlation analysis showed that FC between the left inferior orbitofrontal gyrus and the right rostral hippocampus was significantly negatively correlated with the California Verbal Learning Test (CVLT) and Brief Visuospatial Memory Test (BVMT) scores. The FC between the right rostral hippocampus and the left superior temporal gyrus was negatively correlated with BVMT scores. FC abnormalities in the hippocampal subregions of patients with anti-NMDAR encephalitis were associated with cognitive impairment, emotional changes, and seizures. These results may help explain the pathophysiological mechanisms and clinical manifestations of anti-NMDAR encephalitis and NMDAR dysfunction-related diseases such as schizophrenia.

Intravoxel incoherent motion diffusion-weighted imaging of pancreas: Probing evidence of ß-cell dysfunction in asymptomatic adults with hyperglycemia in vivo.

PURPOSE: Early evaluation of ß-cell dysfunction of hyperglycemic patients in asymptomatic adults would be valuable for timely prevention of the diabetes. This study aimed to evaluate functional changes in the pancreas using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and determine whether it could be used as a non-invasive method of assessing ß-cell dysfunction. METHODS: This prospective cohort study was conducted from August 2022 to November 2022 in Jinan University Affiliated Guangdong Second General Hospital. Three groups were enrolled and underwent IVIM-DWI: confirmed patients with type 2 diabetes (T2DM); hyperglycemic patients in asymptomatic adults; and the volunteers with normal glucose tolerance (NGT). Imaging parameters were obtained: apparent diffusion coefficient (ADC), the true diffusion coefficient (Dt), the pseudo-diffusion coefficient (Dp), and the perfusion fraction (f). The ß-cell function indexes were calculated from blood examinations: composite insulin sensitivity index (ISI), 60-min insulinogenic index (IGI60), and the disposition index (DI). We compared imaging parameters among three groups, calculated the diagnostic performance of them for differentiating different groups, and the reproducibility of them was evaluated using intraclass correlation coefficient (ICC). RESULTS: The imaging parameters except f gradually decreased among the groups with significant differences for ADC (p < 0.0001), Dt (p < 0.0001), and Dp (p = 0.013). Dt demonstrated the best diagnostic performance for differentiating asymptomatic patients from NGT (Area Under Curve [AUC] = 0.815, p < 0.0001). IVIM-DWI parameters correlated with composite ISI and DI, of which, Dt has the highest correlation with DI (Pearson correlation coefficient [r] = 0.546, p < 0.0001). The ICC of IVIM-DWI parameters was very good, Dt was highest (Interobserver ICC = 0.938, 95% Confidence Interval [CI], 0.899-0.963; Intraobserver ICC = 0.941, 95% CI, 0.904-0.965). CONCLUSION: IVIM-DWI is a non-invasive quantitative method that can identify ß-cell dysfunction in the pancreas.

Motor Control Exercise Modulates the Neural Plasticity of the Default Mode Network in Patients with Chronic Low Back Pain.

BACKGROUND: Motor control exercise (MCE) effectively alleviates nonspecific chronic low back pain (CLBP), but the neural mechanisms underlying this phenomenon are poorly understood. OBJECTIVE: To study MCE's neural mechanisms in patients with CLBP by resting-state functional magnetic resonance imaging (rs-fMRI). STUDY DESIGN: A prospective, single-blind, randomized, controlled trial. SETTING: Department of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat-sen University. METHODS: 58 patients were randomly assigned to either the MCE or the Manual Therapy (MT) group. Before and after treatment, all the patients underwent ultrasound imaging to measure transversus abdominis (TrA) activation, rs-fMRI scans and questionnaire assessments. We analyzed the activation and connectivity of the bilateral precuneus based on the fractional amplitude of low-frequency fluctuation (fALFF) and effective connectivity (EC) analyses. Further, we determined the association between imaging and clinical measures. RESULTS: Pain intensity, pain catastrophizing, and pain-related disability were alleviated significantly in both groups post-treatment. However, the MCE group showed a greater reduction in pain-related disability and a better improvement in activation of the right TrA than the MT group. After MCE, patients showed an increase in regional fALFF values in the key node of the default mode network (bilateral precuneus) and decreased EC from the bilateral precuneus to the key node of the frontoparietal network (the left dorsolateral prefrontal cortex (DLPFC)). The pre-to-post-treatment change in the EC from bilateral precuneus into the left DLPFC was significantly correlated with the pre-to-post-treatment change in visual analog scale scores and activation of the right TrA in the MCE group (r = 0.765, P < 0.001 and r = 0.481 and P = 0.043 respectively). LIMITATIONS: The present study showes the correlation between the alteration of brain functions and CLBP-related symptoms, which does not reveal the causal effect between them. Further, this study does not estimate the long-term efficacy of MCE on brain function, and the sample size was not calculated based on fMRI data. CONCLUSION: These findings demonstrate that MCE may alleviate CLBP symptoms in patients by modifying information transmission from the default mode network to the left frontoparietal network.

Mn(II) Optimized Sono/Chemodynamic Effect of Porphyrin-Metal-Organic Framework Nanosheets for MRI-Guided Colon Cancer Therapy and Metastasis Suppression.

Sonodynamic therapy (SDT) offers a remarkable non-invasive ultrasound (US) treatment by activating sonosensitizer and generating reactive oxygen species (ROS) to inhibit tumor growth. The development of multifunctional, biocompatible, and highly effective sonosensitizers remains a current priority for SDT. Herein, the first report that Mn(II) ions chelated Gd-TCPP (GMT) nanosheets (NSs) are synthesized via a simple reflux method and encapsulated with pluronic F-127 to form novel sonosensitizers (GMTF). The GMTF NSs produce a high yield of ROS under US irradiation due to the decreased highest occupied molecular orbital-lowest unoccupied molecular orbital gap energy (2.7-1.28 eV). Moreover, Mn(II) ions endow GMTF with a fascinating Fenton-like activity to produce hydroxyl radicals in support of chemodynamic therapy (CDT). It is also effectively used in magnetic resonance imaging (MRI) with high relaxation rate (r 1: 4.401 mM-1 s-1) to track the accumulation of NSs in tumors. In vivo results indicate that the SDT and CDT in combination with programmed cell death protein 1 antibody (anti-PD-1) show effective metastasis prevention effects, and 70% of the mice in the GMTF + US + anti-PD-1 group survived for 60 days. In conclusion, this study develops a sonosensitizer with promising potential for utilizing both MRI-guided SDT and CDT strategies.

Multi-omics integrative analysis revealed characteristic changes in blood cell immunity and amino acid metabolism in a silkworm model of hyperproteinemia.

Hyperproteinemia is a serious metabolic disease of both humans and animals characterized by an abnormally high plasma protein concentration (HPPC). Although hyperproteinemia can cause an imbalance in blood cell homeostasis, the functional changes to blood cells remain unclear. Here, a HPPC silkworm model was used to assess changes to the chromatin accessibility and transcript levels of genes related to blood cell metabolism and immune function. The results showed that HPPC enhanced phagocytosis of blood cells, increased chromatin accessibility and transcript levels of genes involved in cell phagocytosis, proliferation, stress, and programmed death, while genes associated with aromatic amino acid metabolism, and antibacterial peptide synthesis were inhibited in blood cells. Further analysis of the chromatin accessibility of the promoter region found that the high chromatin accessibility of genes sensitive to HPPC, was related to histone modifications, including tri-methylation of lysine residue 4 of histone H3 and acetylation of lysine residue 27 of histone H3. Changes to the chromatin accessibility and transcript levels of genes related to immune function and amino acid metabolism in the blood cells of the HPPC silkworm model provided useful references for future studies of the mechanisms underlying epigenomic regulation mediated by hyperproteinemia.

Imaging investigation of cervicocranial artery dissection by using high resolution magnetic resonance VWI and MRA: qualitative and quantitative analysis at different stages.

BACKGROUND: To explore the value of magnetic resonance angiography (MRA) and high resolution magnetic resonance vessel wall imaging (HRMR-VWI) in cervicocranial artery dissection (CCAD) for the disease diagnosis, course staging and treatment. On the basis of qualitative evaluation, this study also extract the changes of different stages in vessel wall in different vessel segments to identify imaging indicators for the quantitative evaluation of CCAD. METHODS: We retrospectively enrolled 34 patients with CCAD (38branches) with conventional MRA and HRMR-VWI examinations. Two radiologists independently analyzed imaging features of vessel wall and lumen in the different stages, and the typical sign detection of artery dissection were compared between MRA and HRMR-VWI. Then the parameters of vessel wall was quantitatively evaluated by the post-processing software (Vesselmass, Leiden University Medical Center, Leiden, The Netherlands. RESULTS: HRMR-VWI revealed typical sign detection of artery dissection in all patients in the acute and subacute stage. Among them, the intimal flap/double lumen sign ditection were more common than the MRA, there was significant difference (P = 0.012). MRA revealed typical sign detection of artery dissection in more than half the patients, and the detection was no significant difference at the chronic stage between MRA and HRMR-VWI (P = 1.000/1.000/0.761). In the acute and subacute stage, the typical sign detection of intramural hematoma and Grade II enhancement revealed by HR-MRI was higher than the observations in the chronic stage (P = 0.000/0.000/0.016), while there was no significant difference by MRA (P = 0.902). The values of wall thickness, relative signal intensity of vessel wall enhancement, relative signal intensity of intramural hematoma (IMH), and percentage of stenosis in CCAD decreased from acute to subacute and then to chronic stages. Each quantitative parameter in patients with CCAD in the early stages (i.e., acute and subacute stages) was significantly different from that in patients with CCAD in the recovered group at chronic stage (P < 0.05). Wall thickness and relative signal intensity of vessel wall enhancement in patients with CCAD in the early stages were not significantly different from those in patients with CCAD in the incompletely recovered group at chronic stage (P > 0.05). CONCLUSIONS: As the only noninvasive imaging technology, HRMR-VWI displays the structure of the vessel wall in vivo, showing not only excellent performance in the early diagnosis of CCAD, but also describing the changes of different stages in the qualitative and quantitative characteristics of vessel wall. It also helps to guide the diseasediagnosis, course staging and treatment of CCAD. Although the diagnostic efficacy of MRA was not as good as HRMR-VWI, it should be the first choice of method for routine examination in evaluating CCAD, especially at the chronic stage of CCAD.

Dual-targeting nanotheranostics for MRI-guided enhanced chemodynamic therapy of hepatoma via regulating the tumor microenvironment.

Chemodynamic therapy (CDT), as a reactive oxygen species (ROS)-based therapeutic modality, has attracted much attention in recent years. However, the insufficient therapeutic effect of CDT is due to the antioxidant system in the tumor microenvironment, such as high levels of glutathione (GSH). In this study, we developed a biological/physical dual-targeting nanotheranostic agent (relaxation rate, r1: 6.3 mM-1 s-1 and r2: 13.11 mM-1 s-1) for enhanced CDT of SMCC-7721 tumors. This nanotheranostic agent is composed of a homologous tumor cell membrane (TCM), magnetic ferric oxide, and manganese oxide and is denoted as FM@TCM nanoparticles (NPs). A favorable effect of in vitro CDT on SMCC-7721 cells (IC50: 20 µg mL-1) is demonstrated, attributed to the Fenton reaction and oxidative stress resulting from the reduction of the GSH level. In vivo T1/T2 magnetic resonance imaging (MRI) confirms that the tumor accumulation of FM@TCM NPs is promoted by concurrent bioactive targeting of the homologous TCM and physico-magnetic targeting of tumor tissues with an external magnetic field. Impressive chemodynamic therapeutic effects on SMCC-7721 tumors are demonstrated through the catalysis of endogenous hydrogen peroxide and depletion of GSH to generate high levels of ROS. Dual-targeting FM@TCM NPs inhibit SMCC-7721 tumor growth (∼90.9%) in vivo without any biotoxicity. This nanotheranostic agent has great potential for use in MRI-guided CDT.

Mechanism of hyperproteinemia-induced damage to female reproduction in a genetic silkworm model.

Hyperproteinemia is a metabolic disorder characterized by abnormally elevated plasma protein concentrations (PPC) in humans and animals. Here, a genetic silkworm model with high PPC was employed to investigate the effect of elevated PPC on female reproduction. Transcriptomic analysis revealed that high PPC induces downregulation of the ovarian development-related genes and disrupts ovarian sugar metabolism. Biochemical and endocrinal analyses revealed that high PPC increases trehalose and glucose levels in hemolymph and glycogen content in the fat body through activation of the gluconeogenic pathway and inhibition of the Insulin/Insulin-like growth factor signaling pathway-the serine/threonine kinase (IIS-AKT) pathway, thus disrupting characteristic metabolic homeostasis of sugar in the ovary. These resulted in ovarian developmental delay as well as reduced number and poor quality of eggs. Insulin supplementation effectively increased egg numbers by lowering blood sugar. These collective results provide new insights into the mechanisms by which high PPC negatively affects female reproduction and support the potential therapeutic effects of insulin.

Functional Alterations of the Basal Ganglia Are Associated with Voluntary Activation of the Core Stabilizing Muscles in Patients with Chronic Low Back Pain: A Cross-Sectional Study.

Purpose: Deficits in voluntary activation of the core stabilizing muscles are consistently observed in patients with chronic low back pain (CLBP); however, the underlying neural mechanism remains unclear. This cross-sectional study aimed at testing the hypothesis that the impaired voluntary activation of core stabilizing muscles is associated with structural and functional alterations in the basal ganglia, thalamus, and cortex in patients with CLBP. Methods: We obtained structural and resting-state functional magnetic resonance imaging (rs-fMRI) data from 53 patients with CLBP and 67 healthy controls and estimated the alterations in grey matter volume (GMV) and functional and effective connectivity (EC) of regions with altered GMV via whole brain analysis. The voluntary activation of the multifidus (MF) and transversus abdominis (TrA) was evaluated by ultrasound imaging in these patients. Results: Compared with the HCs, they displayed a significant decrease in GMV in the bilateral thalamus and caudate nucleus, a significant increase in GMV in the left middle frontal gyrus, and increased resting-state functional connectivity between the right caudate nucleus and the bilateral precuneus (voxel-level p < 0.005, Gaussian random field-corrected p < 0.05). The patients also showed increased EC from the right caudate nucleus to the bilateral precuneus, which was significantly correlated with voluntary activation of the bilateral MF and TrA (all p < 0.050). Conclusions: Grey matter alterations may be confined to regions responsible for perception, motor control, and emotion regulation in patients with CLBP. The interrupted EC from the basal ganglia to the default mode network might be involved in the impairment of voluntary activation of the core stabilizing muscles.

DNA methylation mediated by RdDM pathway and demethylation affects furanone accumulation through regulation of QUINONE OXIDOREDUCTASE in strawberry.

Recently, increasing evidence suggests that DNA methylation plays a crucial role in fruit ripening. However, the role of DNA methylation in regulating specific traits, such as flavor, remains unclear. Here, we report a role of DNA methylation in affecting furanone biosynthesis in strawberry. Strawberry quinone oxidoreductase (FaQR) is a key enzyme in furanone biosynthesis. There are four FaQR homologs in strawberry cultivar 'Yuexin', and one of them, FaQR3, contributes ~50% of FaQR transcripts, indicating a major role of FaQR3 in furanone biosynthesis. Through characterization of levels of DNA methylation and FaQR3 transcript and furanone contents during fruit ripening and after the application of DNA methylation inhibitor, we found that the DNA methylation level of the FaQR3 promoter was negatively correlated with FaQR3 expression and furanone accumulation, suggesting that DNA methylation may be involved in furanone biosynthesis through adjusting FaQR3 expression, and responded to different temperatures consistently. In addition, transient expression of a gene in the RNA-directed DNA methylation (RdDM) pathway, FaAGO4, and enrichment analysis of the 24-nucleotide siRNAs suggested that DNA methylation in the FaQR3 promoter is mediated by the RdDM pathway. Transient RNA interference (RNAi) of FaDML indicated that the demethylation pathway may be involved in regulating furanone accumulation. These findings provide new insights into the role of DNA methylation and demethylation in affecting flavor quality in strawberry during fruit ripening.

Aberrant single-subject morphological cerebellar connectome in chronic insomnia.

BACKGROUND: To systematically investigate the topological organisation of morphological networks of the cerebellum using structural MRI and examine their clinical relevance in chronic insomnia (CI). METHODS: One hundred and one patients with CI and 102 healthy controls (HCs) were recruited in this study. Individual morphological networks of the cerebellum were constructed based on regional grey matter volume, and topologically characterised using weighted graph theory-based network approaches. Between-group comparisons were performed using permutation tests, and Spearman's correlation was used to examine the relationships between topological alterations and clinical variables. RESULTS: Compared with HCs, patients with CI exhibited a lower normalised clustering coefficient. Locally, CI patients exhibited lower nodal efficiency in the cerebellar lobule VIIb and vermis regions, but higher nodal efficiency in the right cerebellar lobule VIIIa regions. No correlations were observed between network alterations and clinical variables. CONCLUSIONS: Individual morphological network analysis provides a new strategy for investigating cerebellar morphometric changes in CI, and our findings may have important implications in establishing diagnostic and categorical biomarkers.

Aberrant spontaneous brain activity in patients with thyroid-associated ophthalmopathy with and without optic neuropathy: a resting-state functional MRI study.

OBJECTIVES: To investigate the brain functional alterations in dysthyroid optic neuropathy (DON) by evaluating spontaneous neural activity, using functional magnetic resonance imaging (fMRI) with regional homogeneity (ReHo), and its relationship with ophthalmologic performance. METHODS: Forty-seven patients with thyroid-associated ophthalmopathy (TAO; 20 with DON, 27 with non-DON) and 33 age-, sex-, and education-matched healthy controls (HCs) underwent fMRI. ReHo values were compared using one-way analysis of variance (ANOVA) with post hoc pairwise comparisons (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). Correlations between ReHo values and ophthalmological metrics were assessed for DONs, with Bonferroni correction for multiple comparisons (p < 0.004). ROC curves were applied to evaluate the diagnostic performance of ReHo metrics. RESULTS: ReHo values were significantly lower in the left insula and right superior temporal gyrus, and higher in the left posterior cingulate cortex (LPCC), of DON than of non-DON patients. ReHo values were also significantly lower in the right middle temporal, left insula, and left precentral gyrus in DON than in HCs. Meanwhile, ReHo values were higher in LPCC in non-DON than in HCs. ReHo values correlated with ophthalmic examinations to varying degrees in DON. For distinguishing DON, the ReHo values in LPCC showed optimal individually (AUC = 0.843), the combination of the ReHo in both the left insula and LPCC performed better (AUC = 0.915). CONCLUSION: Spontaneous brain activity differed between TAO with and without DON, which may reflect the underlying pathological mechanism of DON. The ReHo index can be considered a diagnostic biomarker. CLINICAL RELEVANCE STATEMENT: Spontaneous brain activity in DON differed from that in TAO without DON, which may reflect the underlying pathological mechanism of DON. The ReHo index can be considered a diagnostic biomarker for early detection of DON. KEY POINTS: • Dysthyroid optic neuropathy (DON) affects brain activity, which contributes in the understanding of its visual dysfunction. • Regional homogeneity values differ between thyroid-associated ophthalmopathy with and without DON in various brain regions. • Regional homogeneity values can be used as a biomarker in the differential diagnosis of DON.

Comprehensive analysis of nanoplastic effects on growth phenotype, nanoplastic accumulation, oxidative stress response, gene expression, and metabolite accumulation in multiple strawberry cultivars.

Nanoplastics (NPs) have emerged as a novel environmental threat due to their potential impacts on both animals and plants. Currently, research on the ecotoxicity of NPs has mainly focused on marine aquatic organisms and freshwater algae, with very limited investigations conducted on horticultural plants. This study examined the effects of varying concentrations (0, 1, 10, 50 mg·L-1) of polystyrene NPs (PS-NPs) on strawberry growth. The findings revealed that low concentrations of PS-NPs stimulated strawberry growth, whereas high concentrations impeded it. Notably, diverse strawberry cultivars displayed considerable differences in their sensitivity to PS-NP exposure. Laser scanning confocal microscopy confirmed the absorption of PS-NPs by strawberry roots, with variations in PS-NP accumulation observed across different cultivars. Comparative transcriptomics analysis suggested that the differential expression of genes responsible for calcium ion transport played a significant role in the observed intervarietal differences in PS-NP accumulation among strawberry cultivars. Furthermore, distinct variations in endogenous oxidative responses were observed in different strawberry cultivars under PS-NP treatment. Further analysis indicated that the down-regulation of peroxidase (POD) gene expression and terpenoid compounds accumulation were responsible for heightened endogenous oxidative stress observed in certain strawberry cultivars under PS-NP treatment. Transcriptomic and metabolomic analyses were performed on six strawberry cultivars to investigate their response to PS-NPs in terms of endogenous gene expression and metabolite accumulation. The results identified one commonly up-regulated gene (wall-associated receptor kinase-like) and sixteen commonly down-regulated genes associated with lipid metabolism and carbohydrate metabolism. In addition, a significant reduction in fatty acid metabolite accumulation was observed in the six strawberry cultivars under PS-NP treatment. These findings have significant implications for understanding the effects of NPs on strawberry growth, metabolism, and antioxidant responses, as well as identifying marker genes for monitoring and evaluating the impact of NP pollution on strawberry.

Procoagulant effect of extracellular vesicles in patients after transcatheter aortic valve replacement or transcatheter aortic valve replacement with percutaneous coronary intervention.

Patients with severe aortic stenosis (AS) after replacement of the transcatheter aortic valve (TAVR) are more likely to develop thrombotic complications such as cerebral embolism and artificial valve thrombosis. However, the mechanism is not yet well defined. We aimed to explore the plasma extracellular vesicles (EVs) levels and their role in the induction of procoagulant activity (PCA) in patients receiving TAVR alone or TAVR with percutaneous coronary intervention (PCI). EVs were analyzed with flow cytometer. Markers of platelet and endothelial cell activation were quantified using selective enzyme-linked immunosorbent assay (ELISA) kits. Procoagulant activity (PCA) was assessed by clotting time, purified clotting complex assays, and fibrin production assays. Our results confirmed that EVs with positive phosphatedylserin (PS+EV), platelet EVs (PEVs) and positive tissue factor EVs (TF+EVs) were higher in patients following TAVR than before TAVR, particularly in TAVR with PCI. Furthermore, endothelial-derived EVs (EEVs) were also higher in patients after TAVR with PCI than pre-TAVR, however, the EEVs levels in TAVR alone patients were gradually reduce than pre-TAVR. In addition, we further proved that total EVs contributed to dramatically shortened coagulation time, increased intrinsic/extrinsic factor Xa and thrombin generation in patients after TAVR, especially in TAVR with PCI. The PCA was markedly attenuated by approximately 80% with lactucin. Our study reveals a previously unrecognized link between plasma EV levels and hypercoagulability in patients after TAVR, especially TAVR with PCI. Blockade of PS+EVs may improve the hypercoagulable state and prognosis of patients.

Aberrant brain entropy in posttraumatic stress disorder comorbid with major depressive disorder during the coronavirus disease 2019 pandemic.

Aim: Previously, neuroimaging studies on comorbid Posttraumatic-Major depression disorder (PTSD-MDD) comorbidity found abnormalities in multiple brain regions among patients. Recent neuroimaging studies have revealed dynamic nature on human brain activity during resting state, and entropy as an indicator of dynamic regularity may provide a new perspective for studying abnormalities of brain function among PTSD-MDD patients. During the COVID-19 pandemic, there has been a significant increase in the number of patients with PTSD-MDD. We have decided to conduct research on resting-state brain functional activity of patients who developed PTSD-MDD during this period using entropy. Methods: Thirty three patients with PTSD-MDD and 36 matched TCs were recruited. PTSD and depression symptoms were assessed using multiple clinical scales. All subjects underwent functional magnetic resonance imaging (fMRI) scans. And the brain entropy (BEN) maps were calculated using the BEN mapping toolbox. A two-sample t-test was used to compare the differences in the brain entropy between the PTSD-MDD comorbidity group and TC group. Furthermore, correlation analysis was conducted between the BEN changes in patients with PTSD-MDD and clinical scales. Results: Compared to the TCs, PTSD-MDD patients had a reduced BEN in the right middle frontal orbital gyrus (R_MFOG), left putamen, and right inferior frontal gyrus, opercular part (R_IFOG). Furthermore, a higher BEN in the R_MFOG was related to higher CAPS and HAMD-24 scores in the patients with PTSD-MDD. Conclusion: The results showed that the R_MFOG is a potential marker for showing the symptom severity of PTSD-MDD comorbidity. Consequently, PTSD-MDD may have reduced BEN in frontal and basal ganglia regions which are related to emotional dysregulation and cognitive deficits.