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1.
Ecotoxicol Environ Saf ; 207: 111490, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33120278

RESUMO

Benzene is a ubiquitous, occupational, and environmental hematotoxic and leukemogen. Damage to hematopoietic stem cells (HSCs) induced by benzene and its metabolites is a key event in bone marrow (BM) depression and leukemogenesis. There are no reports on transcriptome profiles of HSCs following benzene exposure. Here, Smart-seq2 single-cell transcriptome sequencing was used to detect transcriptomic alternations in BM HSCs and peripheral blood HSCs (PBSCs) in male C57B/6 mice exposed to benzene. We found that benzene caused hematotoxicity which was confirmed by routine blood test, pathological examination, and HSCs percentage analysis. A total of 1514 differentially expressed genes (DEGs) in BM HSCs and 1703 DEGs in PBSCs were screened after treatment with benzene. Weighted gene correlation network analysis revealed that pathways in cancer, transcriptional misregulation in cancer, and hematopoietic cell lineage are vital pathways involved in benzene-induced toxicity in BM HSCs, whereas hematopoietic cell lineage and leukocyte transendothelial migration are critical pathways in PBSCs. Of note, there were 164 common DEGs in both HSCs, out of which 53 genes were co-regulated in both types of HSCs. Subsequent pathway analysis of these 53 genes indicated that the most relevant pathways involved neutrophil degranulation and CD93 localized in the core of the network of the 53 genes, which are known to regulate leukemia stem cell self-renewal and quiescence. Our results could enhance our understanding of HSC responses to benzene, facilitate the identification of potential molecular biomarkers and future studies on its mechanism of toxicity toward HSCs.

2.
J Hazard Mater ; 402: 123454, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32683159

RESUMO

For typical copper producing provinces of Heilongjiang, Henan, Inner Mongolia, Jiangxi, Shandong, Tibet, and Yunnan in China, 90 % of sampling sites were heavily polluted with multiple heavy metals. Soil heterogeneity and mutual interference of multimetals are obstacles to explore bacterial resistance pathways in contaminated field soils. Through analyses of contamination indices and bioindicators, combined with multivariate statistical models, the antioxidant enzyme activity, urease-induced precipitation of heavy metals, excretion of extracellular polymeric substances (EPS) were attributed to different types of heavy metals. Furthermore, through redundancy analysis combined with phylogenetic analysis of metal-resistant bacteria, we identified that Verrucomicrobia, Acidobacteria, and Planctomycetes secreted EPS-polysaccharides and EPS-proteins to detoxify Cr, a metal with lower concentrations and lower ecological risk as compared to other metals. The pathway was innovatively differentiated from the multimetal resistance pathways in urease and/or catalase-producing bacteria such as Proteobacteria, Firmicutes, BRC1, Bacteroidetes, Dadabacteria, Entotheonellaeota, Nitrospirae, and Gemmatimonadetes using field studies and high-throughput sequencing. Moreover, these metal-resistant bacteria were linked to C/N cycling processes of urea hydrolysis, nitrification, denitrification, EPS production, and calcite precipitation. It will provide new insight into soil bacterial resistance to multimetals in field studies.

3.
Diabetes Ther ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216280

RESUMO

INTRODUCTION: East Asians are more susceptible to early-onset diabetes than Europeans and exhibit reduced insulin secretion at earlier stages. PAX4 plays a critical role in the development of ß-cells. The dysfunction-missense variants PAX4 R192H and PAX4 R192S are common in East Asians but rare in Europeans. Therefore, we aim to investigate the diabetes-associated genes, including PAX4 R192H/S, in East Asians with early-onset diabetes. METHODS: Exome variants of 80 Chinese early-onset diabetes patients (onset age < 35 years) after the exclusion of type 1 diabetes (T1D) were detected by a customized gene panel covering 32 known diabetes-associated genes. Then, 229 subjects with early-onset diabetes (T1D excluded) and 1679 controls from the Chinese population were genotyped to validate the association of PAX4 R192H/S with early-onset diabetes and related phenotypes. RESULTS: The gene panel detected 11 monogenic diabetes patients with five novel mutations among the 80 early-onset diabetes patients. Asian-specifically enriched PAX4 R192H and R192S were associated with early-onset diabetes (R192H: OR 1.88, 95% CI 1.37-2.60, P = 8.41 × 10-5; R192S: OR 1.71, 95% CI 1.17-2.51, P = 0.005). In early-onset diabetes patients, PAX4 R192H carriers had higher haemoglobin A1c (HbA1c) levels (P = 0.030) and lower 2 h C-peptide levels in the oral glucose tolerance test (OGTT) (P = 0.040); R192S carriers had lower fasting C-peptide (FCP) (P = 0.011) and 2 h C-peptide levels (P = 0.033) in OGTT than non-variant carriers. CONCLUSIONS: The ethnic-specific enrichment of PAX4 R192H/S predisposing East Asians to early-onset diabetes with decreased C-peptide levels may be one explanation of the discrepancy of diabetes between East Asians and Europeans. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01938365).

4.
Clin Sci (Lond) ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201243

RESUMO

The AML1-ETO oncoprotein, which results from t(8;21) translocation, is considered an initial event of t(8;21) acute myeloid leukemia (AML). However, the precise mechanisms of the oncogenic activity of AML1-ETO has yet to be fully determined. This study demonstrates that AML1-ETO triggers the heterochromatic silencing of microRNA-564 (miR564) by binding at the AML1 binding site along the miR564 promoter region and recruiting chromatin-remodeling enzymes. Suppression of miR564 enhances the oncogenic activity of the AML1-ETO oncoprotein by directly inhibiting the expression of CCND1 and the DNMT3A gene. Ectopic expression of miR564 can induce retardation of G1/S transition, reperform differentiation, promote apoptosis, as well as inhibit the proliferation and colony formation of AML1-ETO+ leukemia cells in vitro. Enhanced miR564 levels can significantly inhibit the tumor proliferation of t(8;21)AML in vivo. We first identify an unexpected and important epigenetic circuitry of AML1-ETO/miR564/CCND1/DNMT3A that contributes to the leukemogenesis in vitro/vivo of AML1-ETO+ leukemia, indicating that miR564 enhancement could provide a potential therapeutic method for AML1-ETO+ leukemia.

5.
Medicine (Baltimore) ; 99(47): e23295, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217860

RESUMO

BACKGROUND: Temporomandibular disorders (TMD) is a common physical and psychological disease in dental department. Pain and mandibular limitation are the main reasons for patients to seek oral treatment. However, the presence of kinesiophobia, patients often catastrophize pain, so as to avoid mandibular movement, which seriously affects their quality of life. Cognitive behavioral therapy (CBT) has significant improvements in reducing kinesiophobia and quality of life in musculoskeletal disease, but has not been proved in TMD patients. The study aims to apply CBT on kinesiophobia and oral health related quality of life (OHRQOL) in TMD patients. METHODS: A total of 108 individuals between 18 and 65 years of age, who will be referred to the temporomandibular joint clinic of Stomatology Hospital of Tianjin Medical University in china will be randomized into 2 treatment arms. The control group will receive a conventional treatment, whereas the experiment group will receive CBT on the basis of the control group. The primary outcomes will be the kinesiophobia and OHRQOL, and will be measured by the Tampa scale for kinesiophobia for patients with Temporomandibular Disorders (TSK-TMD) and the Oral Health Impact Scale for patients with temporomandibular disorders (OHIP-TMDs), the secondary outcomes will be pain intensity measured by Numerical Rating Scale (NRS), pain catastrophizing measured by Pain Catastrophizing Scale (PCS), anxiety and depression measured by Hospital Anxiety and Depression Scale (HADS), and self-efficacy measured by General Self-Efficacy Scale (GSES). DISCUSSION: This study protocol reported a randomized controlled trial which aimed at assessing the effectiveness of the CBT versus conventional treatment with TMD. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registration Center with the number ChiCTR2000038573. Registered 24 September 2020.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33180916

RESUMO

CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors in which altered central metabolism appears to be a major driver of tumorigenesis, and many PPGL genes encode proteins involved in the tricarboxylic acid (TCA) cycle. OBJECTIVE/DESIGN: While around 40% of PPGL cases carry a variant in a known gene, many cases remain unexplained. In unexplained patients showing clear evidence of a familial burden or multiple tumors, we aimed to identify causative factors using genetic analysis of patient DNA and functional analyses of identified DNA variants in patient tumor material and engineered cell lines. PATIENTS AND SETTING: Patients with a likely familial cancer burden of pheochromocytomas and/or paragangliomas and under investigation in a clinical genetic and clinical research setting in university hospitals. RESULTS: While investigating unexplained PPGL cases, we identified a novel variant, c.1151C>T, p.(Pro384Leu), in exon 14 of the gene encoding dihydrolipoamide S-succinyltransferase (DLST), a component of the multi-enzyme complex 2-oxoglutarate dehydrogenase. Targeted sequence analysis of further unexplained cases identified a patient carrying a tumor with compound heterozygous variants in DLST, consisting of a germline variant, c.1121G>A, p.(Gly374Glu), together with a somatic missense variant identified in tumor DNA, c.1147A>G, p.(Thr383Ala), both located in exon 14. Using a range of in silico and functional assays we show that these variants are predicted to be pathogenic, profoundly impact enzyme activity and result in DNA hypermethylation. CONCLUSIONS: The identification and functional analysis of these DLST variants further validates DLST as an additional PPGL gene involved in the TCA cycle.

7.
Sci Total Environ ; : 143236, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33187716

RESUMO

Perchlorate (ClO4-) in water is an emerging contaminant that threatens human health by inhibiting the uptake of iodine in the thyroid gland. Biopolymer adsorbents including chitosan hydrogel beads (CSBs) have attracted increasing attentions in water treatment for their low costs, ease in preparation, and environmental friendliness. However, the adsorption capacity for ClO4- by several crosslinked CSBs has been shown to be low. To overcome this, epichlorohydrin (ECH) crosslinked CSBs (ECH-CSBs) that preserved -NH2 functional groups as potential sites for adsorption are synthesized and characterized, followed by batch adsorption experiments to evaluate adsorption and desorption reactions. The point of zero charge is determined to be 5.1 ± 0.1. Both XPS spectra and DFT calculations support that electrostatic interaction between ClO4- and protonated -NH3+ functional groups is responsible for adsorption that reaches a capacity of 63.4 to 76.3 mg/g between pH of 4.0-10.0 at 303.15 K that follows Langmuir isotherm. ECH crosslinking also enhances hydrophilicity of CSBs to allow for increased adsorption for ClO4-. Adsorption of ClO4- (10 and 100 mg/L) follows a pseudo-first order kinetics with equilibrium time of 2-6 h but is limited by intra-particle diffusion. Anions common in natural waters exhibit interference effects due to similar electrostatic attraction mechanism, thus HCO3- and SO42- with high abundance in natural waters need pre-treatment. Regeneration of the adsorbents to 100% of its adsorption capacity by rinsing with 0.1 M NaOH is demonstrated for 12 cycles due to complete desorption of ClO4- via electrostatic repulsion, assuring reusability.

8.
BMC Psychiatry ; 20(1): 545, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225936

RESUMO

BACKGROUND: With an estimated > 800,000 suicide-related deaths and potentially several attempts for each death in the world. The purpose of this study was to determine the epidemiological characteristics of self-poisoning with pesticides within the Jiangsu province in China. METHODS: Suicide rate was calculated the Routine Surveillance System by Jiangsu Provincial Center for Disease Control and Prevention, stratified by gender, age and region, combined with socioeconomic and agriculture-related factors to investigate trends in suicide over the study period. A logistic regression model was used to investigate the associations between pesticide types and pesticide-related deaths. RESULTS: In recent years, Jiangsu Province has witnessed a decrease in pesticide self-poisoning cases and consequent deaths. Among all suicides by deliberate ingestion of pesticides, the proportion of cases were mainly in the age 40, accounting for 3.43% of all cases with pesticide suicide. The proportion of suicide due to pesticide poisoning in females was markedly higher than that in males (p < 0.001). Suicide using organophosphate and carbamate insecticides was most common, with 10,303 reported cases accounting for 42.02% of all suicides. CONCLUSIONS: For national responses to be effective, the characteristics of pesticide suicides should be comprehensively investigated for the formulation of corresponding prevention strategies. At present, more pesticide suicide prevention policies for the elderly people and women should be implemented, and stronger pesticide management policies should be implemented for rural areas.

9.
Immunol Res ; 68(6): 325-339, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33161557

RESUMO

Antibodies are considered as an excellent foundation to neutralize pathogens and as highly specific therapeutic agents. Antibodies are generated in response to a vaccine but little use as immunotherapy to combat virus infections. A new generation of broadly cross-reactive and highly potent antibodies has led to a unique chance for them to be used as a medical intervention. Neutralizing antibodies (monoclonal and polyclonal antibodies) are desirable for pharmaceutical products because of their ability to target specific epitopes with their variable domains by precise neutralization mechanisms. The isolation of neutralizing antiviral antibodies has been achieved by Phage displayed antibody libraries, transgenic mice, B cell approaches, and hybridoma technology. Antibody engineering technologies have led to efficacy improvements, to further boost antibody in vivo activities. "Although neutralizing antiviral antibodies have some limitations that hinder their full development as therapeutic agents, the potential for prevention and treatment of infections, including a range of viruses (HIV, Ebola, MERS-COV, CHIKV, SARS-CoV, and SARS-CoV2), are being actively pursued in human clinical trials."

10.
Exp Gerontol ; 142: 111114, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33132156

RESUMO

PURPOSE: To characterize the changes of retinal microvascular density and their relations to cognitive function in the healthy older people without known cognitive impairment after an 8-week high-speed circuit resistance training program (HSCT). METHODS: Twenty cognitively normal older people were recruited and randomly assigned to either the HSCT group or control group (CON). Twelve subjects (age 70.8 ± 5.8 yrs) in the HSCT group trained three times per week for 8 weeks. Eight subjects in the CON group (age 71.8 ± 4.8 yrs) did not perform formal training. Both eyes of each subject were imaged using optical coherence tomography angiography (OCTA) at baseline and at 8-week follow-up. The densities of the retinal vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP) were measured. In addition, their cognitive functions were tested using the NIH toolbox. RESULTS: There were significant increases in pattern comparison processing speed (PAT, P = 0.02) and fluid composite score (FCS, P = 0.005) at the follow-up in the HSCT group. Although the vessel densities did not differ between visits in either group, the variation (i.e., change) in retinal vessel density of SVP was negatively related to the changes of FCS (r = -0.54, P = 0.007) and the List Sorting Working Memory test (r = -0.43, P = 0.039) in the HSCT group. CONCLUSIONS: This is the first study to reveal that the individual response of the SVD was related to the improvement in the cognition in cognitively normal older people after HSCT.

11.
Medicine (Baltimore) ; 99(46): e23198, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181698

RESUMO

BACKGROUND: COVID-9 has become a global pandemic with severe health issues around the world. However, there is still no effective drug to treat the disease, and many studies have shown that moxibustion plays a positive role in adjuvant treatment of COVID-19. Therefore, this meta-analysis is designed to evaluate the efficacy of moxibustion for COVID-19. METHODS: The relevant randomized controlled trials will be systematically retrieved from the electronic database, including PubMed, Embase, Cochrane Clinical Trials Database, Web of Science, and China National Knowledge Infrastructure, without restrictions on publication status and language. Two reviewers will independently review all included studies and assess the risk of bias. Two reviewers will independently extract data from the included studies based on a pre-designed standardized form. Any disagreements will be resolved by consensus. The meta-analysis will be performed with RevMan (V5.3.5) software. RESULT: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This ongoing meta-analysis will provide up-to-date evidence of the efficacy of moxibustion for patients with COVID-19. REGISTRATION: The meta-analysis has been prospectively registered in PROSPERO (CRD42020211910).

12.
Commun Biol ; 3(1): 687, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33214666

RESUMO

Vascular leakage, or edema, is a serious complication of acute allergic reactions. Vascular leakage is triggered by the release of histamine and serotonin from granules within tissue-resident mast cells. Here, we show that expression of Neutrophil Serine Protease 4 (NSP4) during the early stages of mast cell development regulates mast cell-mediated vascular leakage. In myeloid precursors, the granulocyte-macrophage progenitors (GMPs), loss of NSP4 results in the decrease of cellular levels of histamine, serotonin and heparin/heparan sulfate. Mast cells that are derived from NSP4-deficient GMPs have abnormal secretory granule morphology and a sustained reduction in histamine and serotonin levels. Consequently, in passive cutaneous anaphylaxis and acute arthritis models, mast cell-mediated vascular leakage in the skin and joints is substantially reduced in NSP4-deficient mice. Our findings reveal that NSP4 is required for the proper storage of vasoactive amines in mast cell granules, which impacts mast cell-dependent vascular leakage in mouse models of immune complex-mediated diseases.

13.
Crit Rev Food Sci Nutr ; : 1-17, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146022

RESUMO

With the continuous improvements in human diet, there is an ever-increasing demand for high-quality chicken, so it is particularly important for poultry breeders to carry out the breeding of high-quality broilers in a timely fashion. Inosine monophosphate (IMP) is a flavor-enhancing substance, which plays a critical role in the umami taste of the muscle, making the content of IMP an important umami taste indicator. Currently, research on the deposition mechanism of IMP in chicken is not only necessary for chicken breeders to promote the production of high-quality meat and poultry but also to meet the human demand for chicken meat. In this paper, the research history of IMP, its structure and taste mechanisms, the pathway and influencing factors of de novo IMP synthesis, and the key genes regulating IMP synthesis and metabolism are briefly summarized. Our aim was to lay a theoretical foundation and provide scientific background and research directions for further research on high-quality broiler breeding.

14.
Sci Adv ; 6(43)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33087359

RESUMO

Growing evidence suggests that autism spectrum disorder (ASD) is strongly associated with dysbiosis in the gut microbiome, with the exact mechanisms still unclear. We have proposed a novel analytic strategy-quasi-paired cohort-and applied it to a metagenomic study of the ASD microbiome. By comparing paired samples of ASD and neurotypical subjects, we have identified significant deficiencies in ASD children in detoxifying enzymes and pathways, which show a strong correlation with biomarkers of mitochondrial dysfunction. Diagnostic models based on these detoxifying enzymes accurately distinguished ASD individuals from controls, and the dysfunction score inferred from the model increased with the clinical rating scores of ASD. In summary, our results suggest a previously undiscovered potential role of impaired intestinal microbial detoxification in toxin accumulation and mitochondrial dysfunction, a core component of ASD pathogenesis. These findings pave the way for designing future therapeutic strategies to restore microbial detoxification capabilities for patients with ASD.

15.
PLoS One ; 15(10): e0241310, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33119648

RESUMO

Silicosis is a systemic disease characterized by chronic persistent inflammation and incurable pulmonary fibrosis with the underlying molecular mechanisms to be fully elucidated. In this study, we employed tandem mass tag (TMT) based on quantitative proteomics technology to detect differentially expressed proteins (DEPs) in lung tissues of silica-exposed rats. A total of 285 DEPs (145 upregulated and 140 downregulated) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the biological pathway and functional classification of the proteins. Results showed that these DEPs were mainly enriched in the phagosome, lysosome function, complement and the coagulation cascade, glutathione metabolism, focal adhesion and ECM-receptor interactions. To validate the proteomics data, we selected and analyzed the expression trends of six proteins including CD14, PSAP, GM2A, COL1A1, ITGA8 and CLDN5 using parallel reaction monitoring (PRM). The consistent result between PRM and TMT indicated the reliability of our proteomic data. These findings will help to reveal the pathogenesis of silicosis and provide potential therapeutic targets. Data are available via ProteomeXchange with identifier PXD020625.

16.
Acta Biochim Biophys Sin (Shanghai) ; 52(10): 1156-1165, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33083831

RESUMO

The central nervous system (CNS) diseases are still a major cause of morbidity and mortality throughout the world, which imposes heavy burden on the development of society. Ethionine is a non-proteinogenic amino acid having similar chemical structure and activity to that of methionine, with which it competes. Previous studies have confirmed that ethionine affects various cellular functions by inhibiting the biosynthesis of proteins, RNA, DNA, and phospholipids, or all of them. The relationship of ethionine with some CNS diseases, including neural tube defects, has been investigated recently. However, the detailed effects of ethionine on the nerve cell bioactivities and the underlying mechanisms have not been fully explored. Herein, we systematically investigated the influences of ethionine on the proliferation, differentiation, and apoptosis of neural stem cells (NSCs) and post-mitotic nerve cells. We demonstrated that ethionine inhibited cell viability by disrupting the balance between proliferation and apoptosis, prevented NSCs from differentiating into neurons and astrocytes, and blocked cell progression from G1 to S phase via reducing cyclin D1 function in nerve cells including NSCs, a mouse hippocampal neuron cell line (HT-22), and a mouse brain neuroma cell line (Neuro-2a). We speculated that the inhibitory effect of ethionine on cell viability and differentiation are associated with increased reactive oxygen species production. Our results also supported the concept that ethionine may be an underlying cause of abnormal folate metabolism-induced CNS diseases. Our findings may provide important direction for the application of abnormal folate metabolism-induced CNS diseases in future NSC-based therapies.

17.
FASEB J ; 34(12): 15822-15836, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33103304

RESUMO

Retinopathy of prematurity (ROP) is a vision-threatening disorder characterized with retinal vaso-obliteration in phase 1 and pathological neovascularization (NV) in phase 2. However, there has been no effective and safe treatment for ROP. Current management is mainly focused on the reduction of abnormal NV in phase 2, and anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment, yet, with great risks of late recurrence and systemic side effects. It has been reported that the severity of vaso-obliteration in phase 1 largely influences subsequent NV, suggesting that it may be a promising target to develop novel treatments for ROP. Here, we investigated the therapeutic potential and safety of early rapamycin intervention in treating phase 1 ROP and possible underlying mechanisms using the mouse model of oxygen-induced retinopathy (OIR). We found that intravitreal injection of rapamycin at postnatal day 7 (P7) significantly reduced retinal avascular area, increased vascular density, and reversed the suppression of deep capillaries development in phase 1 of OIR mice. Rapamycin treatment not only reduced vascular apoptosis, but also promoted proliferation and tip cell functions. Additionally, rapamycin did not interfere with normal retinal vascular development. Further investigation showed that Ang1/Tie2 pathway might be involved in rapamycin's vascular protection in phase 1 OIR retinas. Moreover, early rapamycin treatment at P7 had long-term protective effects of reducing retinal NV and avascular area, as well as enhancing vascular maturity in phase 2 of OIR mice. Together, our data suggest that rapamycin may be a safe and promising strategy for early intervention of ROP.

18.
Neural Plast ; 2020: 8882207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082780

RESUMO

The current study is aimed at establishing links between brain network examination and neural plasticity studies measured by optical neuroimaging. Sixteen healthy subjects were recruited from the University of Macau to test the Granger Prediction Estimation (GPE) method to investigate brain network connectivity during figurative language comprehension. The method is aimed at mapping significant causal relationships across language brain networks, captured by functional near-infrared spectroscopy measurements (fNIRS): (i) definition of regions of interest (ROIs) based on significant channels extracted from spatial activation maps; (ii) inspection of significant causal relationships in temporal resolution, exploring the experimental task agreement; and (iii) early identification of stronger causal relationships that guide neuromodulation intervention, targeting impaired connectivity pathways. Our results propose top-down mechanisms responsible for perceptive-attention engagement in the left anterior frontal cortex and bottom-up mechanism in the right hemispheres during the semantic integration of figurative language. Moreover, the interhemispheric directional flow suggests a right hemisphere engagement in decoding unfamiliar literal sentences and fine-grained integration guided by the left hemisphere to reduce ambiguity in meaningless words. Finally, bottom-up mechanisms seem activated by logographic-semantic processing in literal meanings and memory storage centres in meaningless comprehension. To sum up, our main findings reveal that the Granger Prediction Estimation (GPE) integrated strategy proposes an effective link between assessment and intervention, capable of enhancing the efficiency of the treatment in language disorders and reducing the neuromodulation side effects.

20.
Dis Markers ; 2020: 2032056, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101541

RESUMO

Substantial advance supports that CMTM2 serve as an important performer in physiological and pathological processes. However, very little is clear about the relationship between CMTM2 and HBV-related disorders. Here, for the first time, we explore that whether or not serum CMTM2 is involved in HBV-related diseases. We found that CMTM2 values were significantly lower in patients compared to healthy control (p <0.001), using ELISA assay. Furthermore, serum CMTM2 levels were negatively correlated with HBV DNA levels in CHB patients but not correlated with the serum levels of ALT and AST. Serum CMTM2 concentrations were not correlated with the serum levels of ALT, AST and HBV DNA load in HBLC and HCC patients. In addition, analysis of the ROC curve indicated that CMTM2 levels were significantly associated with the diagnostic value of HBV-related disorders. Finally, downregulation of CMTM2 was observed in HBV-infected cell model. CMTM2 degradation could be attributed to HBx-activated Lys48 (K48)-linked polyubiquitination, which was abolished by treatment with the proteasome inhibitor MG132. HBV infection suppresses CMTM2 expression by activating ubiquitin-proteasome system. Serum CMTM2 levels can be adopted as an effective indicator of the pathogenesis of HBV-related disorders.

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