Targeting of KOR by famotidine promotes OPC maturation differentiation and CNS remyelination via STAT3 signaling pathway.

This study aims to identify FDA-approved drugs that can target the kappa-opioid receptor (KOR) for the treatment of demyelinating diseases. Demyelinating diseases are characterized by myelin sheath destruction or formation that results in severe neurological dysfunction. Remission of this disease is largely dependent on the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLGs) in demyelinating lesions. KOR is an important regulatory protein and drug target for the treatment of demyelinating diseases. However, no drug targeting KOR has been developed due to the long clinical trials for drug discovery. Here, a structure-based virtual screening was applied to identify drugs targeting KOR among 1843 drugs of FDA-approved drug libraries, and famotidine was screen out by its high affinity cooperation with KOR as well as the clinical safety. We discovered that famotidine directly promoted OPC maturation and remyelination using the complementary in vitro and in vivo models. Administration of famotidine was not only effectively enhanced CNS myelinogenesis, but also promoted remyelination. Mechanically speaking, famotidine promoted myelinogenesis or remyelination through KOR/STAT3 signaling pathway. In general, our study provided evidence of new clinical applicability of famotidine for the treatment of demyelinating diseases for which there is currently no effective therapy.

Experimental study on the effect of Coumarone resin on the performance of SBS-modified asphalt.

An inexpensive and high-performing solid Coumarone resin was added to Styrene-butadiene-styrene (SBS) copolymer-modified asphalt to enhance its storage stability and road performance. To assess the effect of Coumarone resin dosage on the SBS-modified asphalt, a series of laboratory tests were conducted. The composite modified asphalt's segregation test was used to evaluate its storage stability, Dynamic Shear Rheometer (DSR) and Multiple Stress Creep Recovery (MSCR) tests were employed to investigate its high-temperature performance and permanent deformation resistance, and the Bending Beam Rheology (BBR) test was utilized to measure its low-temperature performance. Fluorescence microscopy was used to observe the composite modified asphalt's microstructure, and Fourier Transform Infrared Spectroscopy (FTIR) was conducted to study the changes in chemical structure during the modification process. The results showed that Coumarone resin can improve the compatibility of SBS and asphalt, improve the high-temperature performance and deformation resistance of SBS-modified asphalt, and adding an appropriate amount of Coumarone resin can help enhance the low-temperature cracking resistance of modified asphalt. The optimal dosage of Coumarone resin recommended for SBS-modified asphalt performance enhancement is 2% under the test conditions, as determined by comparing the test results of samples with various dosages.

Abnormal degree centrality as a potential imaging biomarker for ischemic stroke: A resting-state functional magnetic resonance imaging study.

OBJECTIVE: To explore degree centrality (DC) abnormalities in ischemic stroke patients and determine whether these abnormalities have potential value in understanding the pathological mechanisms of ischemic stroke patients. METHODS: Sixteen ischemic stroke patients and 22 healthy controls (HCs) underwent resting state functional magnetic resonance imaging (rs-fMRI) scanning, and the resulting data were subjected to DC analysis. Then we conducted a correlation analysis between DC values and neuropsychological test scores, including Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Finally, extracted the abnormal DC values of brain regions and defined them as features for support vector machine (SVM) analysis. RESULTS: Compared with HCs, ischemic stroke patients showed increased DC in the bilateral supplementary motor area, and median cingulate and paracingulate gyri and decreased DC in the left postcentral gyrus, right calcarine fissure and surrounding cortex, lingual gyrus, and orbital parts of the right superior frontal gyrus and bilateral cuneus. Correlation analyses revealed that DC values in the right lingual gyrus, calcarine fissure and surrounding cortex, and orbital parts of the right superior frontal gyrus were positively correlated with the MMSE scores. The SVM classification of the DC values achieved an area under the curve (AUC) of 0.93, an accuracy of 89.47%. CONCLUSION: Our research results indicate that ischemic stroke patients exhibit abnormalities in the global connectivity mechanisms and patterns of the brain network. These abnormal changes may provide neuroimaging evidence for stroke-related motor, visual, and cognitive impairments, contribute to a deeper comprehension of the underlying pathophysiological mechanisms implicated in ischemic stroke.

Changes in Resting-State Networks in Children with Growth Hormone Deficiency.

Purpose: Growth hormone deficiency (GHD) refers to the partial or complete lack of growth hormone. Short stature and slow growth are characteristic of patients with GHD. Previous neuroimaging studies have suggested that GHD may cause cognitive and behavioral impairments in patients. Resting-state networks (RSNs) are regions of the brain that exhibit synchronous activity and are closely related to our cognition and behavior. Therefore, the purpose of the current study was to explore cognitive and behavioral abnormalities in children with GHD by investigating changes in RSNs. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data of 26 children with GHD and 15 healthy controls (HCs) were obtained. Independent component analysis was used to identify seven RSNs from rs-fMRI data. Group differences in RSNs were estimated using two-sample t-tests. Correlation analysis was employed to investigate the associations among the areas of difference and clinical measures. Results: Compared with HCs, children with GHD had significant differences in the salience network (SN), default mode network (DMN), language network (LN), and sensorimotor network (SMN). Moreover, within the SN, the functional connectivity (FC) value of the right posterior supramarginal gyrus was negatively correlated with the adrenocorticotropic hormone and the FC value of the left anterior inferior parietal gyrus was positively correlated with insulin-like growth factor 1. Conclusions: These results suggest that alterations in RSNs may account for abnormal cognition and behavior in children with GHD, such as decreased motor function, language withdrawal, anxiety, and social anxiety. These findings provide neuroimaging support for uncovering the pathophysiological mechanisms of GHD in children. Impact statement Children with growth hormone deficiency (GHD) generally experience cognitive and behavioral abnormalities. However, there are few neuroimaging studies on children with GHD. Moreover, prior research has not investigated the aberrant brain function in patients with GHD from the perspective of brain functional networks. Therefore, this study employed the independent component analysis method to investigate alterations within seven commonly observed resting-state networks due to GHD. The results showed that children with GHD had significant differences in the salience network, default mode network, language network, and sensorimotor network. This provides neuroimaging support for revealing the pathophysiological mechanisms of GHD in children.

Dynamic analysis of amplitude of low-frequency fluctuation in children with growth hormone deficiency.

OBJECTIVE: Growth hormone (GH) affects brain activities and promotes growth and development. GH is a peptide hormone secreted by the anterior pituitary gland and is tied to behavior and cognitive function. Growth hormone deficiency (GHD) is the most common type of pathological short stature in children. Existing studies provide evidence that GHD may impact functional brain activities. The aim of this study was to investigate dynamic local brain activity in GHD children. METHOD: In this study, we combined amplitude of low-frequency fluctuations (ALFF) and sliding-window techniques to examine the local brain activity of children with GHD. The resting-state functional magnetic resonance imaging (fMRI) data were collected from 26 children with GHD and 15 age- and sex-matched healthy controls (HC). RESULT: Our results showed significant abnormal temporal variability of dynamic ALFF in widespread regions in children with GHD, primarily in the frontal gyrus, temporal gyrus, and parietal lobule. CONCLUSION: The dALFF can capture dynamic changes in brain spontaneous activity, which are related to behavior and cognition. Based on this dynamic local brain activity, the results of this study provide a better understanding of the pathophysiological mechanism in children with GHD.

Frequency Dependent Changes of Regional Homogeneity in Children with Growth Hormone Deficiency.

Abnormal spontaneous neural activity in children with growth hormone deficiency (GHD) has been found in previous resting-state functional magnetic resonance imaging (rs-fMRI) studies. Nevertheless, the spontaneous neural activity of GHD in different frequency bands is still unclear. Here, we combined rs-fMRI and regional homogeneity (ReHo) methods to analyze the spontaneous neural activity of 26 GHD children and 15 healthy controls (HCs) with age- and sex-matching in four frequency bands: slow-5 (0.014-0.031 Hz), slow-4 (0.031-0.081 Hz), slow-3 (0.081-0.224 Hz), and slow-2 (0.224-0.25 Hz). In the slow-5 band, GHD children compared with HCs displayed higher ReHo in the left dorsolateral part of the superior frontal gyrus, triangular part of the inferior frontal gyrus, precentral gyrus and middle frontal gyrus, and right angular gyrus, while lower ReHo in the right precentral gyrus, and several medial orbitofrontal regions. In the slow-4 band, GHD children relative to HCs revealed increased ReHo in the right middle temporal gyrus, whereas reduced ReHo in the left superior parietal gyrus, right middle occipital gyrus, and bilateral medial parts of the superior frontal gyrus. In the slow-2 band, compared with HCs, GHD children showed increased ReHo in the right anterior cingulate gyrus, and several prefrontal regions, while decreased ReHo in the left middle occipital gyrus, and right fusiform gyrus and anterior cingulate gyrus. Our findings demonstrate that regional brain activity in GHD children exhibits extensive abnormalities, and these abnormalities are related to specific frequency bands, which may provide bases for understanding its pathophysiology significance.

Frequency specificity in the amplitude of low frequency oscillations in patients with white matter lesions.

Previous studies have reported that patients with white matter lesions (WMLs) have abnormal spontaneous brain activity in the resting state. However, the spontaneous neuronal activity of specific frequency bands in WMLs patients is unknown. Here, we included 16 WMLs patients and 13 gender and age-matched healthy controls (HCs) underwent resting-state magnetic resonance imaging (rs-fMRI) scan and studied the specificity of the amplitude of low-frequency fluctuations (ALFF) in WMLs patients in the slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), and typical (0.01-0.08 Hz) frequency bands. In addition, ALFF values of different frequency bands were extracted as classification features and support vector machines (SVM) were used to classify WMLs patients. In all three frequency bands, significant increases in ALFF values in WMLs patients were observed in the cerebellum. In the slow-5 band, the ALFF values of the left anterior cingulate and paracingulate gyri (ACG), and the right precentral gyrus, rolandic operculum and inferior temporal gyrus in WMLs patients were lower than those in HCs. In the slow-4 band, ALFF values were lower in WMLs patients than in HCs at the left ACG, the right median cingulate and paracingulate gyri, parahippocampal gyrus, caudate nucleus, and the bilateral lenticular nucleus, putamen. In the SVM classification model, the classification accuracy of slow-5, slow-4 and typical frequency bands is 75.86%, 86.21% and 72.41%, respectively. The results indicate that the ALFF abnormalities in WMLs patients have frequency specificity, and the ALFF abnormalities in the slow-4 frequency band may serve as imaging markers for WMLs.

Synthesis of biochar@α-Fe2O3@Shewanella loihica complex for remediation of soil contaminated by hexavalent chromium: Optimization of conditions and mechanism.

The reduction of hexavalent chromium combined with the process of dissimilatory iron reduction is an important strategy for microbial remediation of chromium-contaminated soil. However, its applicability is limited by the slow speed of bacterial bioreduction and the toxic effect of heavy metals on bacteria. Here, biochar (BC) was used as a substrate and was loaded with iron oxide in the form of hematite and Shewanella loihica to synthesize a BC@α-Fe2O3@S. loihica complex and thus achieve combined microbial-chemical remediation. After optimization by a Box-Behnken design, the optimal dosages of the complex, humic acid (as an electron shuttle), and sodium lactate (as an electron donor) were found to be 1.38 mL/g, 33.94 mg/g, and 12.95%, respectively. The Cr(VI) reduction rate in soil contaminated with 1000 mg/kg Cr(VI) reached 98.26%, and remediation could be achieved within 7 days. Characterization of the BC@α-Fe2O3@S. loihica complex before and after it was used for remediation by energy-dispersive X-ray spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy proved that the oxygen-containing functional groups and aromatic compounds on the surface of the BC participated in the adsorption and reduction of Cr(VI) and that the loaded hematite particles were fully utilized by microorganisms. Therefore, the BC@α-Fe2O3@S. loihica complex has great potential for the remediation of Cr(VI)-contaminated soil.