Brain network connectivity feature extraction using deep learning for Alzheimer's disease classification.

Early diagnosis and therapeutic intervention for Alzheimer's disease (AD) is currently the only viable option for improving clinical outcomes. Combining structural magnetic resonance imaging (sMRI) and resting-state functional magnetic resonance imaging (rs-fMRI) to diagnose AD has yielded promising results. Most studies assume fixed time lags when constructing functional networks. Since the propagation delays between brain signals are constantly changing, these methods cannot reflect more detailed relationships between brain regions. In this work, we use a deep learning-based Granger causality estimator for brain connectivity construction. It exploits the strength of long short-term memory in ever-changing time series processing. This research involves data analysis from sMRI and rs-fMRI. We use sMRI to analyze the cerebral cortex properties and use rs-fMRI to analyze the graph metrics of functional networks. We extract a small subset of optimal features from both types of data. A support vector machine (SVM) is trained and tested to classify AD (n = 27) from healthy controls (n = 20) using rs-fMRI and sMRI features. Using a subset of optimal features in SVM, we achieve a classification accuracy of 87.23% for sMRI, 78.72% for rs-fMRI, and 91.49% for combined sMRI with rs-fMRI. The results show the potential to identify AD from healthy controls by integrating rs-fMRI and sMRI. The integration of sMRI and rs-fMRI modalities can provide supplemental information to improve the diagnosis of AD relative to either the sMRI or fMRI modalities alone.

Alterations of white matter tracts and topological properties of structural networks in hemifacial spasm.

Hemifacial spasm (HFS) is characterized by involuntary and paroxysmal muscle contractions on the hemiface. It is generally believed that HFS is caused by neurovascular compression at the root exit zone of the facial nerve. In recent years, the structural alterations of brains with HFS have aroused growing concern. However, little attention has been directed towards the possible involvement of specific white matter (WM) tracts and the topological properties of structural networks in HFS. In the present study, diffusion magnetic resonance imaging tractography was utilized to construct structural networks and perform tractometric analysis. The diffusion tensor imaging scalar parameters along with the WM tracts, and the topological parameters of global networks and subnetworks, were assessed in 62 HFS patients and 57 demographically matched healthy controls (HCs). Moreover, we investigated the correlation of these parameters with disease-clinical-level (DCL) and disease-duration-time (DDT) of HFS patients. Compared with HCs, HFS patients had additional hub regions including the amygdala, ventromedial putamen, lateral occipital cortex, and rostral cuneus gyrus. Furthermore, HFS patients showed significant alternations with specific topological properties in some structural subnetworks, including the limbic, default mode, dorsal attention, somato-motor, and control networks, as well as diffusion properties in some WM tracts, including the superior longitudinal fasciculus, cingulum bundle, thalamo-frontal, and corpus callosum. These subnetworks and tracts were associated with the regulation of emotion, motor function, vision, and attention. Notably, we also found that the parameters with subnetworks and tracts exhibited correlations with DCL and DDT. In addition to corroborating previous findings in HFS, this study demonstrates the changed microstructures in specific locations along with the fiber tracts and changed topological properties in structural subnetworks.

New Measures for the Coronavirus Disease 2019 Response: A Lesson From the Wenzhou Experience.

As the outbreak of coronavirus disease 2019 (COVID-19) has spread globally, determining how to prevent the spread is of paramount importance. We reported the effectiveness of different responses of 4 affected cities in preventing the COVID-19 spread. We expect the Wenzhou anti-COVID-19 measures may provide information for cities around the world that are experiencing this epidemic.

Rno-miR-224-5p contributes to 2,2',4,4'-tetrabromodiphenyl ether-induced low triiodothyronine in rats by targeting deiodinases.

Hypothyroidism is commonly associated with substantial adverse impacts on human health, and polybrominated diphenyl ether (PBDE), a kind of classic thyroid hormone disruptor, was speculated to be a potential environmental factor, but its effect on thyroxine metabolism has received little attention. In the present study, we investigated the role and mechanism of rno-miR-224-5p in deiodinase-mediated thyroxine metabolism in rats treated with 2,2',4,4'-tetrabromodiphenyl ether (BDE47), a predominant PBDE congener in humans. BDE47 decreased plasma triiodothyronine (T3) and thyroxine (T4) and increased reverse T3 (rT3) in the rats, and the expression of type 1 deiodinase (DIO1) and type 3 deiodinase (DIO3) increased in both the rats and H4-II-E cells. Rno-miR-224-5p was predicted to target dio1 instead of dio3, according to the TargetScan, miRmap.org and microRNA.org databases. Experiments showed that the rno-miR-224-5p level was decreased by BDE47 in a dose-dependent manner and confirmed that rno-miR-224-5p downregulated both DIO1 and DIO3 in the H4-II-E cells and in the rats, as determined using mimics and an inhibitor of rno-miR-224-5p. Furthermore, DIO1 was observed to be a direct functional target of rno-miR-224-5p, whereas DIO3 was indirectly regulated by rno-miR-224-5p via the phosphorylation of the MAPK/ERK (but not p38 or JNK) pathway. Reportedly, DIO1 and DIO3 act principally as inner-ring deiodinases and are responsible for the conversion of T4 to rT3, but not to T3, and the final clearance of thyroxine (mainly in the form of T2). Our results demonstrated that BDE47 induced low levels of T3 conversion through DIO1 and DIO3, which were regulated by rno-miR-224-5p. The findings suggest a novel additional mechanism of PBDE-induced thyroxine metabolism disorder that differs from that of PBDEs as environmental thyroid disruptors.

Fenvalerate triggers Parkinson-like symptom during zebrafish development through initiation of autophagy and p38 MAPK/mTOR signaling pathway.

Fenvalerate (FEN), one of the most used synthetic pyrethroids, has the potential to interfere with human neural function. However, far too little attention was paid to the mechanism of FEN-induced neurotoxicity. Thus we exposed zebrafish to FEN from 4 to 120 h post fertilization (hpf), and analyzed the morphology and behavior of zebrafish. Our results showed that FEN decreased the survival rate of zebrafish, with increased malformation rates and abnormal behaviors. Furthermore, we found typical parkinson-like symptoms in FEN-exposed zebrafish with increases in parkinson's disease (PD), ubiquitin, and Lewy bodies-relevant genes. We also observed the loss of dopaminergic neurons in both FEN-exposed zebrafish and PC12 cells, which were all associated with PD-like symptoms. Besides, FEN activated autophagy by the enhanced expressions of p-mTOR, and LC3-II but the reduction of p62. Further, FEN initially activated p-p38 MAPK followed by p-mTOR, which triggered the transcription of genes responsible for autophagy process and prompted the Lewy bodies neuron generation leading to the PD-like symptoms. This process was inhibited by both 3-methyladenine (3-MA, an autophagy inhibitor) and SB203580 (a p38 MAPK selective inhibitor) in zebrafish and PC12 cells. These results suggest that FEN might cause parkinson-like symptom during zebrafish development through induction of autophagy and activation of p38 MAPK/mTOR signaling pathway. The study revealed the potential mechanism of FEN-induced neurotoxicity and should give new insights into a significant environmental risk factor of developing parkinson's disease.

Aquaporin 4 deficiency alleviates experimental colitis in mice.

Aquaporin (AQP) 4 is expressed in the basolateral membrane of colonic epithelial cells, and the purpose of this study was to explore the mechanistic role of AQP4 in experimental colitis. Experimental colitis was induced in AQP4 knockout (AQP4-/-) CD-1 mice and AQP4 wild-type (AQP4wt) mice by oral administration of dextran sulfate sodium (DSS). Experimental colitis was clinically established. Compared with AQP4wt mice, AQP4-/- mice showed increased tolerance to DSS-induced experimental colitis, including lesser degree of weight loss, diarrhea and bleeding, lower disease activity index scores, longer colon lengths, and lesser histologic scores. DSS-treated AQP4-/- mice had lower serum levels of IL-6 and TNF, higher IL-10 level, and lesser inflammatory cell infiltration. DSS-treated AQP4-/- mice also had lower immunostaining of NF-κB p65 as well as nuclear levels of p65 and phosphorylated p65. Sequencing of 16S rRNA indicated that DSS-treated AQP4-/- mice maintained intestinal microbial diversity and had higher Firmicutes/Bacteroidetes ratios and greater relative abundance of Erysipelotrichaceae species. These results suggested for the first time that AQP4 deficiency alleviates experimental colitis in mice. Our study helps to understand the pathogenesis of inflammatory bowel diseases, and blocking AQP4 may represent a novel therapeutic approach for ulcerative colitis.-Wang, L., Tang, H., Wang, C., Hu, Y., Wang, S., Shen, L. Aquaporin 4 deficiency alleviates experimental colitis in mice.

Emerging role of long non-coding RNA MALAT1 in predicting clinical outcomes of patients with digestive system malignancies: A meta-analysis.

Digestive system malignancies are the most common cancer types worldwide and exhibit an extremely low overall 5-year survival rate. Therefore, clinically applicable biomarkers for predicting clinical outcome are urgently required. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is abnormally expressed in several cancer types. However, to the best of our knowledge, the association between MALAT1 expression and the prognosis of digestive system malignancies remains unknown. Therefore, the current study performed a meta-analysis to comprehensively summarize the association between MALAT1 expression and digestive system malignancies. A total of 1,157 Asian patients from 12 eligible studies [eight studies that investigated overall survival (OS), two studies that investigated disease-free survival and two studies that investigated both indicators] were analyzed. The present results identified a significant association between MALAT1 abundance and poor OS in patients with digestive system malignancies, with a pooled hazard ratio (HR) of 1.62 [95% confidence interval (CI), 1.35-1.88; P<0.001]. The tumor type, region, sample size and analysis type did not alter the predictive value of MALAT1 as an independent factor for survival. Furthermore, MALAT1 overexpression was an unfavorable prognostic factor for the overall survival of patients with esophageal carcinoma, pancreatic cancer, hepatocellular carcinoma and gastric cancer, with HRs of 1.89 (95% CI, 1.29-2.49), 1.76 (95% CI, 0.89-2.63), 1.46 (95% CI, 0.76-2.17) and 1.41 (95% CI, 1.04-1.78), respectively. In particular, increased MALAT1 expression levels were significantly associated with decreased OS in patients with colorectal cancer (HR, 3.04; 95% CI, 1.77-4.31). In conclusion, lncRNA MALAT1 may be a potential prognostic factor for digestive system malignancies in Asian populations.

Isoliquiritigenin as an antioxidant phytochemical ameliorates the developmental anomalies of zebrafish induced by 2,2',4,4'-tetrabromodiphenyl ether.

2,2',4,4'-Tetrabromodiphenyl ether (BDE47) is the most abundant PBDE congeners in biological samples. It has strong tendencies to bioaccumulate and potentially endangers development of mammals through oxidative stress. Isoliquiritigenin (ISL), an emerging natural chalcone-type flavonoid, possesses various biological and pharmacological properties, including antioxidant, anti-allergic, anti-inflammatory, anti-tumor and estrogenic activities. The purpose of the study is to explore the antioxidant effect of ISL on the amelioration of developmental anomalies induced by BDE47. Zebrafish (Danio rerio) embryos were exposed to BDE47 (1 and 10 µM) and/or ISL (4 µM) for 4 to 120 hours post fertilization (hpf), and the morphology, development, behavior, oxidative stress status and related genes expression were assessed. The results showed that BDE47 contributed to dose-dependent growth retardation and deformities, including delayed hatching, spinal curvature, reduced body length, increased death rate, aberrant behaviors and impaired dark-adapted vision, which were significantly mitigated by ISL. Besides, ISL ameliorated excessive ROS accumulation, and exaggerated the expressions of apoptosis-related genes p53, Bcl-2, caspase 3 and caspase 9 induced by BDE47, suggesting that ISL protected zebrafish from the developmental toxicity of BDE47 by inactivation of programmed apoptosis and activation of antioxidant signaling pathways. Taken together, developing ISL as a dietary supplement might be a promising preventive strategy for the amelioration of developmental toxicity induced by environmental pollutants.

Fenvalerate induces oxidative hepatic lesions through an overload of intracellular calcium triggered by the ERK/IKK/NF-κB pathway.

Fenvalerate (FEN), a mainstream pyrethroid pesticide, was initially recommended as a low-toxicity agent for controlling agricultural and domestic pests. Despite the widespread use of FEN worldwide, little data are available on FEN-induced hepatic lesions and molecular mechanisms. In the present study, we first performed an occupational cross-sectional study on FEN factory workers and found that the levels of serum alanine aminotransferase (ALT) and total antioxidant capacity increased, whereas malondialdehyde decreased in laborers in the working areas where the levels of airborne FEN were much higher compared with the office area. The results were then confirmed by animal experiments that abnormal hepatic histology, increased ALT level, and compromised hepatic oxidative capability were observed in rats exposed to a high concentration of FEN. Furthermore, the bioinformatics analysis of gene microarray in rat liver tissue showed that FEN significantly changed the expressions of genes related to the regulation of intracellular calcium ion homeostasis and the calcium signal pathway. Finally, the functional experiments in Buffalo rat liver (BRL) cells demonstrated that FEN first activated ERK MAPK, followed by IKK and NF-κB, which triggered the transcription of genes responsible for accelerating an overload of intracellular calcium ions, prompted reactive oxygen species generation in the mitochondria, and finally, induced hepatic cellular apoptosis. The calcium signaling pathway and in particular, an overload of intracellular calcium play a critical role in this pathophysiological process via the ERK/IKK/NF-κB pathway. Our study furthers the understanding of the mechanism of FEN-induced hepatic injuries and may have implications in the prevention and control of liver diseases induced by environmental pesticides.-Qiu, L.-L., Wang, C., Yao, S., Li, N., Hu, Y., Yu, Y., Xia, R., Zhu, J., Ji, M., Zhang, Z., Wang S.-L. Fenvalerate induces oxidative hepatic lesions through an overload of intracellular calcium triggered by the ERK/IKK/NF-κB pathway.

Report from China social and ethical influence of some pain: the causes of lower incidences of some pain syndromes in Chinese people.

KIE: Western studies of national differences in pain have indicated that pain tolerance is higher in white than in Asian patients. The authors' clinical experiences in China seem to contradict this conclusion, and they have investigated the incidence or prevalence of some pain syndromes and have made comparisons with Western data. Their findings show that the incidence of most pain syndromes is lower in China than in Western countries. Hu and Fang argue that social and ethical factors have an important influence on pain tolerance. They identify four factors affecting pain tolerance in Chinese patients: (1) Chinese are less alienated from nature than are people in developed countries; (2) traditional teachings emphasize composure and rationality over emotion; (3) a state-provided health insurance system lessens anxiety; and (4) a different practice of medical ethics does not include disclosure and informed consent.^ieng