Differentiation of glioma and solitary brain metastasis: a multi-parameter magnetic resonance imaging study using histogram analysis.

BACKGROUND: Differentiation of glioma and solitary brain metastasis (SBM), which requires biopsy or multi-disciplinary diagnosis, remains sophisticated clinically. Histogram analysis of MR diffusion or molecular imaging hasn't been fully investigated for the differentiation and may have the potential to improve it. METHODS: A total of 65 patients with newly diagnosed glioma or metastases were enrolled. All patients underwent DWI, IVIM, and APTW, as well as the T1W, T2W, T2FLAIR, and contrast-enhanced T1W imaging. The histogram features of apparent diffusion coefficient (ADC) from DWI, slow diffusion coefficient (Dslow), perfusion fraction (frac), fast diffusion coefficient (Dfast) from IVIM, and MTRasym@3.5ppm from APTWI were extracted from the tumor parenchyma and compared between glioma and SBM. Parameters with significant differences were analyzed with the logistics regression and receiver operator curves to explore the optimal model and compare the differentiation performance. RESULTS: Higher ADCkurtosis (P = 0.022), frackurtosis (P<0.001),and fracskewness (P<0.001) were found for glioma, while higher (MTRasym@3.5ppm)10 (P = 0.045), frac10 (P<0.001),frac90 (P = 0.001), fracmean (P<0.001), and fracentropy (P<0.001) were observed for SBM. frackurtosis (OR = 0.431, 95%CI 0.256-0.723, P = 0.002) was independent factor for SBM differentiation. The model combining (MTRasym@3.5ppm)10, frac10, and frackurtosis showed an AUC of 0.857 (sensitivity: 0.857, specificity: 0.750), while the model combined with frac10 and frackurtosis had an AUC of 0.824 (sensitivity: 0.952, specificity: 0.591). There was no statistically significant difference between AUCs from the two models. (Z = -1.14, P = 0.25). CONCLUSIONS: The frac10 and frackurtosis in enhanced tumor region could be used to differentiate glioma and SBM and (MTRasym@3.5ppm)10 helps improving the differentiation specificity.

Mutations of PsPALM1a and PsPALM1b associated with the afila phenotype in Pea.

Semi-leafless represents an advantageous plant architecture in pea breeding due to its ability to enhance resistance to lodging and potentially to powdery mildew. The introduction of semi-leafless pea varieties is considered a seminal advancement in pea breeding over the past half-century. The afila (af) mutation leads to the replacement of lateral leaflets by highly branched tendrils; combined with the semi-dwarfing le mutation, it forms the semi-leafless cultivated variety. In this study, we identified that mutations in two tandemly-arrayed genes encoding Cys(2)His(2) zinc finger transcription factors, PsPALM1a and PsPALM1b, were closely associated with the afila phenotype. These two genes may be deleted in the af mutant. In situ hybridization showed that both genes exhibit specific expression in early leaflet primordia. Furthermore, suppression of PsPALM1a/PsPALM1b resulted in a high frequency of conversion of lateral leaflets into tendrils. In conclusion, our study provides genetic evidence demonstrating that mutations in PsPALM1a and PsPALM1b are responsible for the af locus, contributing to a better understanding of compound leaf formation in peas and offering new insights for breeding applications related to afila.

Decreased circadian fluctuation in cognitive behaviors and synaptic plasticity in APP/PS1 transgenic mice.

Cognitive decline, memory impairment and circadian rhythm disturbance are iconic manifestations of Alzheimer's disease (AD). APPswe/PS1dE9 (APP/PS1) mice, a model of AD, show deficits in multiple learning and memory abilities, synaptic plasticity, and behavioral circadian rhythm, but whether circadian differences in cognitive performance and synaptic plasticity could be affected in AD remain unclear. Here, the cognitive behaviors of 6-month-old APP/PS1 mice were assessed by multiple behavior tests in the rest phase (light period) or active phase (dark period) of the day. The possible electrophysiological mechanism was subsequently investigated by in vivo hippocampal long-term potentiation (LTP) recording, and the locomotor activity rhythm of the mice was detected using wheel-running activities. Compared to wild-type (WT) mice, APP/PS1 mice exhibited long-term spatial memory impairment and in vivo hippocampal LTP suppression. In addition, in APP/PS1 mice, circadian differences in new object recognition memory and LTP were lost, and the circadian difference in long-term spatial memory was decreased, accompanied by a less robust locomotor activity rhythm. These results indicate that the loss of circadian differences in new object recognition memory and the decrease in the circadian difference in long-term spatial memory in APP/PS1 mice, which are closely associated with the loss of the circadian difference in LTP and less robust locomotor activity, might occur early in the course of AD.

Indoor pollution control based on surrogate model for residential buildings.

Individuals typically spend most of their lives indoors, predominantly in spaces like offices and residences. Consequently, prolonged indoor exposure underscores the critical significance of maintaining optimal indoor air quality (IAQ) to safeguard one's health. The primary impediment to attaining efficient regulation of Indoor Air Quality (IAQ) is the challenge of monitoring the IAQ parameters, particularly within the immediate vicinity of an individual's breathing space. Current heating, ventilation, and air conditioning systems lack the ability to rapidly predict and optimize the quality of indoor air. The objective of this study is to acquire the distribution features of indoor pollutants and precise indoor environment data in order to efficiently forecast and enhance the IAQ. To achieve this objective, a proposed surrogate model was developed using computational fluid dynamics (CFD). Notably, the Kriging surrogate model can rapidly predict IAQ while using a limited number of CFD runs. CFD are widely used as numerical simulation methods to obtain the accurate information. Surrogate models can rapidly forecast indoor environmental conditions using CFD simulation data simultaneously. Optimization algorithms can efficiently achieve desirable indoor ambient conditions, offering highly effective and intelligent control techniques for indoor atmospheric ventilation.

Genome-Wide Identification and Expression Analysis of the PHD Finger Gene Family in Pea (Pisum sativum).

The plant homeodomain finger (PHD finger) protein, a type of zinc finger protein extensively distributed in eukaryotes, plays diverse roles in regulating plant growth and development. While PHD finger proteins have been identified in various species, their functions remain largely unexplored in pea (Pisum sativum). In this study, we identified 84 members of the PHD finger gene family in pea, which displayed an uneven distribution across seven chromosomes. Through a comprehensive analysis using data from Arabidopsis thaliana and Medicago truncatula, we categorized the PHD finger proteins into 20 subfamilies via phylogenetic tree analysis. Each subfamily exhibited distinct variations in terms of quantity, genetic structure, conserved domains, and physical and chemical properties. Collinearity analysis revealed conserved evolutionary relationships among the PHD finger genes across the three different species. Furthermore, we identified the conserved and important roles of the subfamily M members in anther development. RT-qPCR and in situ hybridization revealed high expression of the pea subfamily M members PsPHD11 and PsPHD16 in microspores and the tapetum layer. In conclusion, this analysis of the PHD finger family in pea provides valuable guidance for future research on the biological roles of PHD finger proteins in pea and other leguminous plants.

Selective Orexin 2 Receptor Blockade Alleviates Cognitive Impairments and the Pathological Progression of Alzheimer's Disease in 3xTg-AD Mice.

The orexin system is closely related to the pathogenesis of Alzheimer's disease (AD). Orexin-A aggravates cognitive dysfunction and increases amyloid ß (Aß) deposition in AD model mice, but studies of different dual orexin receptor (OXR) antagonists in AD have shown inconsistent results. Our previous study revealed that OX1R blockade aggravates cognitive deficits and pathological progression in 3xTg-AD mice, but the effects of OX2R and its potential mechanism in AD have not been reported. In the present study, OX2R was blocked by oral administration of the selective OX2R antagonist MK-1064, and the effects of OX2R blockade on cognitive dysfunction and neuropsychiatric symptoms in 3xTg-AD mice were evaluated via behavioral tests. Then, immunohistochemistry, western blotting, and ELISA were used to detect Aß deposition, tau phosphorylation, and neuroinflammation, and electrophysiological and wheel-running activity recording were recorded to observe hippocampal synaptic plasticity and circadian rhythm. The results showed that OX2R blockade ameliorated cognitive dysfunction, improved LTP depression, increased the expression of PSD-95, alleviated anxiety- and depression-like behaviors and circadian rhythm disturbances in 3xTg-AD mice, and reduced Aß pathology, tau phosphorylation, and neuroinflammation in the brains of 3xTg-AD mice. These results indicated that chronic OX2R blockade exerts neuroprotective effects in 3xTg-AD mice by reducing AD pathology at least partly through improving circadian rhythm disturbance and the sleep-wake cycle and that OX2R might be a potential target for the prevention and treatment of AD; however, the potential mechanism by which OX2R exerts neuroprotective effects on AD needs to be further investigated.

Amyloid ß-protein suppressed nicotinic acetylcholine receptor-mediated currents in acutely isolated rat hippocampal CA1 pyramidal neurons.

Amyloid ß protein (Aß) is responsible for the deficits of learning and memory in Alzheimer's disease (AD). The high affinity between Aß and nicotinic acetylcholine receptors (nAChRs) suggests that the impairment of cognitive function in AD might be involved in the Aß-induced damage of nAChRs. This study investigated the effects of Aß fragments on nAChR-mediated membrane currents in acutely isolated rat hippocampal pyramidal neurons by using whole-cell patch clamp technique. The results showed that: (1) nonspecific nAChR agonist nicotine, selective α7 nAChR agonist choline, and α4ß2 nAChR agonist epibatidine all effectively evoked inward currents in CA1 neurons at normal resting membrane potential, with different desensitization characteristics; (2) acute application of different concentrations (pM-µM) of Aß25-35, Aß31-35, or Aß35-31 alone did not trigger any membrane current, but pretreatment with 1 µM Aß25-35 and Aß31-35 similarly and reversibly suppressed the nicotine-induced currents; (3) further, choline- and epibatidine-induced currents were also reversibly suppressed by the Aß pretreatment, but more prominent for the choline-induced response. These results demonstrate that the functional activity of both α7 and α4ß2 nAChRs in the membrane of acutely isolated hippocampal neurons was significantly downregulated by Aß treatment, suggesting that nAChRs, especially α7 nAChRs, in the brain may be the important biological targets of neurotoxic Aß in AD. In addition, the similar suppression of nAChR currents by Aß25-35 and Aß31-35 suggests that the sequence 31-35 in Aß molecule may be a shorter active center responsible for the neurotoxicity of Aß in AD.

[Influences of percutaneous coronary intervention on myocardial activity in myocardial infarction patients with different viable myocardium].

OBJECTIVE: To evaluate the effect of percutaneous coronary intervention (PCI) on left ventricular function in patients with different types of myocardial infarction and to explore the correlation factors for the left ventricular function. METHODS: A total of 43 patients diagnosed as acute myocardial infarction were enrolled in this study. The perfusion and delayed enhancement magnetic resonance imaging (DE-MRI) was applied to observe the following parameters before the PCI and at month 6 after the procedure: infarct mass, left ventricular ejection fraction (LVEF) and abnormal wall motion score. The subjects were divided into the following three groups by the transmural extent of myocardial infarction manifested in the DE-MRI: the transmural enhancement group, the nontransmural group and the mixed group. Laboratory test was done to detect the level of endothelin (ET), matrix metal enzyme 9 (MMP-9) and high sensitive C reactive protein (hsCRP) before PCI and at month 6 after the procedure. The t test was used to compare the differences among the groups and the multiple regression analysis was taken to explore the correlation factors for the left ventricular function. RESULTS: Compared with the parameters before PCI, the infarct mass after PCI significantly decreased in the nontransmural group and the mixed group [(4.0 ± 2.9) g/cm(3) vs (9.8 ± 5.6) g/cm(3) and (6.0 ± 3.5) g/cm(3) vs (11.8 ± 6.2)g/cm(3), all P < 0.05], while LVEF was significantly improved after PCI in both groups [(52.6 ± 15.4)% vs (41.9 ± 16.3)%,(45.6 ± 15.4)% vs (38.9 ± 16.3)%, all P < 0.05]. The infarct mass was an independent correlation factor for LVEF before PCI (RR = 0.318, P < 0.05) and LVEF after PCI (RR = 0.293, P < 0.05) . LVEF before PCI was independently correlated with the level of hsCRP (RR = 0.318, P < 0.05). CONCLUSION: The effect of PCI on the improvement of left ventricular function differs in patients with different extent of myocardial infarction, which is correlated with the amount of survival myocardium and the inflammatory factors.

A bilevel data-driven method for sewer deposit prediction under uncertainty.

Deposit accumulation is one of the predominant causes of sewer blockage and overflow. Nevertheless, the traditional detection methods are costly and time-consuming, and the accuracy of the mathematical models for deposit prediction is usually affected by some uncertain factors (e.g., pipe properties and flow velocity of water). This paper proposes a framework of global sensitivity analysis (GSA) to identify the most sensitive indicators for sewer deposit prediction by (i) developing a data-driven bilevel (i.e., catchment level and segment level) model to map the relation between input and output indicators and (ii) employing three different GSA methods, namely, the Morris method, Sobol method, and Borgonovo index method to identify the indicators as important or unimportant (insensitive). The results show that the likelihood of combined sewer overflow occurrences (LCSOO), pipe age (PA), and pipe material (PM) are influential parameters for the thickness of deposits. Here, we pay close attention to the most influential parameters, which can help improve forecast prediction accuracy.

Control of compound leaf patterning by MULTI-PINNATE LEAF1 (MPL1) in chickpea.

Plant lateral organs are often elaborated through repetitive formation of developmental units, which progress robustly in predetermined patterns along their axes. Leaflets in compound leaves provide an example of such units that are generated sequentially along the longitudinal axis, in species-specific patterns. In this context, we explored the molecular mechanisms underlying an acropetal mode of leaflet initiation in chickpea pinnate compound leaf patterning. By analyzing naturally occurring mutants multi-pinnate leaf1 (mpl1) that develop higher-ordered pinnate leaves with more than forty leaflets, we show that MPL1 encoding a C2H2-zinc finger protein sculpts a morphogenetic gradient along the proximodistal axis of the early leaf primordium, thereby conferring the acropetal leaflet formation. This is achieved by defining the spatiotemporal expression pattern of CaLEAFY, a key regulator of leaflet initiation, and also perhaps by modulating the auxin signaling pathway. Our work provides novel molecular insights into the sequential progression of leaflet formation.

Multimodal MRI-Based Radiomic Nomogram for the Early Differentiation of Recurrence and Pseudoprogression of High-Grade Glioma.

Objective: To evaluate the diagnostic value of multimodal MRI radiomics based on T2-weighted fluid attenuated inversion recovery imaging (T2WI-FLAIR) combined with T1-weighted contrast enhanced imaging (T1WI-CE) in the early differentiation of high-grade glioma recurrence from pseudoprogression. Methods: A total of one hundred eighteen patients with brain gliomas who were diagnosed from March 2014 to April 2020 were retrospectively analyzed. According to the clinical characteristics, the patients were randomly split into a training group (n = 83) and a test group (n = 35) at a 7 : 3 ratio. The region of interest (ROI) was delineated, and 2632 radiomic features were extracted. We used multiple logistic regression to establish a classification model, including the T1 model, T2 model, and T1 + T2 model, to differentiate recurrence from pseudoprogression. The diagnostic efficiency of the model was evaluated by calculating the area under the receiver operating characteristic curve (AUC) and accuracy (ACC) and by analyzing the calibration curve of the nomogram and decision curve. Results: There were 75 cases of recurrence and 43 cases of pseudoprogression. The diagnostic efficacies of the multimodal MRI-based radiomic model were relatively high. The AUC values and ACC of the training group were 0.831 and 77.11%, respectively, and the AUC values and ACC of the test group were 0.829 and 88.57%, respectively. The calibration curve of the nomogram showed that the discrimination probability was consistent with the actual occurrence in the training group, and the discrimination probability was roughly the same as the actual occurrence in the test group. In the decision curve analysis, the T1 + T2 model showed greater overall net efficiency. Conclusion: The multimodal MRI radiomic model has relatively high efficiency in the early differentiation of recurrence from pseudoprogression, and it could be helpful for clinicians in devising correct treatment plans so that patients can be treated in a timely and accurate manner.

Do the combination of multiparametric MRI-based radiomics and selected blood inflammatory markers predict the grade and proliferation in glioma patients?

PURPOSE: We aimed to explore whether multiparametric magnetic resonance imaging (MRI)-based radiomics combined with selected blood inflammatory markers could effectively predict the grade and proliferation in glioma patients. METHODS: This retrospective study included 152 patients histopathologically diagnosed with glioma. Stratified sampling was used to divide all patients into a training cohort (n=107) and a validation cohort (n=45) according to a ratio of 7:3, and five-fold repeat cross-validation was adopted in the training cohort. Multiparametric MRI and clinical parameters, including age, the neutrophil-lymphocyte ratio and red cell distribution width, were assessed. During image processing, image registration and gray normalization were conducted. A radiomics analysis was performed by extracting 1584 multiparametric MRI-based features, and the least absolute shrinkage and selection operator (LASSO) was applied to generate a radiomics signature for predicting grade and Ki-67 index in both training and validation cohorts. Statistical analysis included analysis of variance, Pearson correlation, intraclass correlation coefficient, multivariate logistic regression, Hosmer-Lemeshow test, and receiver operating characteristic (ROC) curve. RESULTS: The radiomics signature demonstrated good performance in both the training and validation cohorts, with areas under the ROC curve (AUCs) of 0.92, 0.91, and 0.94 and 0.94, 0.75, and 0.82 for differentiating between low and high grade gliomas, grade III and grade IV gliomas, and low Ki-67 and high Ki-67, respectively, and was better than the clinical model; the AUCs of the combined model were 0.93, 0.91, and 0.95 and 0.94, 0.76, and 0.80, respectively. CONCLUSION: Both the radiomics signature and combined model showed high diagnostic efficacy and outperformed the clinical model. The clinical factors did not provide additional improvement in the prediction of the grade and proliferation index in glioma patients, but the stability was improved.

Conventional MR and DW imaging findings of cerebellar primary CNS lymphoma: comparison with high-grade glioma.

Primary central nervous system lymphomas (PCNSLs) and high-grade gliomas (HGGs) arising in the cerebellum is extremely low, making the differential diagnosis difficult or even impossible. The purpose of this study was to define the MR features of cerebellar PCNSL in immunocompetent patients, and to determine whether a combination of conventional MR and DW imaging can assist in the differentiation of PCNSLs and HGGs. Twelve PCNSLs and 15 HGGs confirmed by pathological analysis were retrospectively identified. The apparent diffusion coefficient (ADC) and conventional MRI parameters were compared for differences between PCNSL and HGG groups using the independent sample t test or chi-square test. Both ADCmin and ADCtotal values were lower in the PCNSL group than those in the HGG group (ADCmin: 0.53 × 10-3 vs. 0.83 × 10-3 mm2/sec, P < 0.001; ADCtotal: 0.66 × 10-3 vs. 0.98 × 10-3 mm2/sec, P = 0.001). As for conventional MR features, there were significant difference in the tumor size, enhancement patterns, the presence of cystic changes, edema degree and streak-like edema (all P < 0.01); but there were no significant difference in lesion type, the presence of bleeding, and involvement of brain surface between two groups (P = 0.554, 0.657 and 0.157, respectively). The results revealed that several conventional MR features, including enhancement patterns, branch-like enhancement and streak-like edema may be useful for the differentiation of PCNSL and HGG in cerebellum and, when combined with ADC values, further improve the discriminating ability.

Suvorexant ameliorates cognitive impairments and pathology in APP/PS1 transgenic mice.

Cognitive impairments and circadian rhythm disorders are the main clinical manifestations of Alzheimer's disease (AD). Orexin has been reported as abnormally elevated in the cerebrospinal fluid of AD patients, accompanied with cognitive impairments. Our recent research revealed that suvorexant, a dual orexin receptor antagonist, could improve behavioral circadian rhythm disorders in 9-month-old APP/PS1 mice. Here we further observed whether suvorexant could ameliorate the cognitive decline in APP/PS1 mice by using behavioral tests, and investigated the possible mechanisms by in vivo electrophysiological recording, western blot, and immunochemistry. The results showed that suvorexant treatment effectively ameliorated the cognitive impairments, alleviated in vivo hippocampal long-term potentiation suppression, restored the circadian phosphorylated CREB expression in the hippocampus, and reduced amyloid-ß protein deposition in the hippocampus and cortex in APP/PS1 mice. These results indicate that the neuroprotective effects of suvorexant against AD are involved in the reduction of amyloid-ß plaques, improvement of synaptic plasticity, and circadian expression of phosphorylated CREB, suggesting that suvorexant could be beneficial to the prevention and treatment of AD.

Co-injection of Aß1-40 and ApoE4 impaired spatial memory and hippocampal long-term potentiation in rats.

Apolipoprotein E4 (APOE4) allele located on chromosome 19 is a major genetic risk factor for developing Alzheimer's disease (AD). However, the direct effects of ApoE4 on the cognitive function and long-term synaptic plasticity have not fully investigated. At the same time, although amyloid beta protein (Aß)-ApoE complexes are principal components of AD-associated brain damage, there is still lack of in vivo study on the effects of co-existed Aß1-40 and ApoE4. In the present study, we examined the effects of ApoE4 on the spatial memory and hippocampal long term potentiation (LTP) by using Morris water maze test and in vivo field potential recording, compared the neurotoxicity of Aß1-40 and ApoE4, and investigated the effects of co-application of Aß1-40 and ApoE4 on cognitive behavior and synaptic plasticity. The results showed that intracerebrovenrticular (i.c.v.) injection of Aß1-40 or ApoE4 significantly and similarly impaired spatial learning and memory, and depressed the high-frequency stimulus (HFS) induced LTP. Importantly, compared to the effects of Aß1-40 or ApoE4 alone, co-injection of Aß1-40 and ApoE4 produced much heavier damages in cognitive behaviors and long term synaptic plasticity. These results demonstrated that ApoE4 not only exerted direct neurotoxicity but also enhanced the neurotoxicity of Aß1-40 on spatial cognitive function and hippocampal LTP, which maybe partly elucidates the mechanism by which APOE4 allele exerted negative effects as a major genetic risk factor for developing AD.

Colivelin Ameliorates Impairments in Cognitive Behaviors and Synaptic Plasticity in APP/PS1 Transgenic Mice.

Alzheimer's disease (AD) is the most common cause of dementia, and effective therapeutics are lacking. Colivelin (CLN), a novel, strong humanin derivative, is effective in vitro in preventing cell death induced by AD-causative genes and amyloid-ß protein (Aß) even at a low concentration. We recently demonstrated that intrahippocampal injection of CLN prevents Aß25-35-induced deficits in spatial memory and synaptic plasticity in normal rats. Here, we further observed the effects of chronically intranasally (i.n.) administered CLN on cognitive behaviors and pathological hallmarks in 9-month-old APPswe/PS1dE9 (APP/PS1) AD mice using multiple behavioral tests and immunochemistry. The electrophysiological mechanism of CLN neuroprotection was also investigated by recording in vivo hippocampal long-term potentiation (LTP). CLN pretreatment effectively prevented impairments in new object recognition, working memory, and long-term spatial memory and reversed the depression of in vivo hippocampal LTP in APP/PS1 mice. Additionally, chronic application of CLN obviously reduced Aß deposition in the hippocampus in APP/PS1 mice. These results indicate that CLN has strong neuroprotective effects on learning and memory behaviors in APP/PS1 mice and that this behavioral improvement is closely associated with the reduction of Aß deposition and alleviation of LTP suppression in the hippocampus, supporting the potential of CLN for the prevention and treatment of AD.