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1.
Brief Bioinform ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31686106

RESUMO

Genes are unique in functional role and differ in their sensitivities to genetic defects, but with difficulties in pathogenicity prediction. This study attempted to improve the performance of existing in silico algorithms and find a common solution based on individualization strategy. We initiated the individualization with the epilepsy-related SCN1A variants by sub-regional stratification. SCN1A missense variants related to epilepsy were retrieved from mutation databases, and benign missense variants were collected from ExAC database. Predictions were performed by using 10 traditional tools with stepwise optimizations. Model predictive ability was evaluated using the five-fold cross-validations on variants of SCN1A, SCN2A, and KCNQ2. Additional validation was performed in SCN1A variants of damage-confirmed/familial epilepsy. The performance of commonly used predictors was less satisfactory for SCN1A with accuracy less than 80% and varied dramatically by functional domains of Nav1.1. Multistep individualized optimizations, including cutoff resetting, domain-based stratification, and combination of predicting algorithms, significantly increased predictive performance. Similar improvements were obtained for variants in SCN2A and KCNQ2. The predictive performance of the recently developed ensemble tools, such as Mendelian clinically applicable pathogenicity, combined annotation-dependent depletion and Eigen, was also improved dramatically by application of the strategy with molecular sub-regional stratification. The prediction scores of SCN1A variants showed linear correlations with the degree of functional defects and the severity of clinical phenotypes. This study highlights the need of individualized optimization with molecular sub-regional stratification for each gene in practice.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31668794

RESUMO

BACKGROUND: Tuberculosis (TB) is a serious opportunistic infection in liver transplant (LT) recipients with a high rate of morbidity and mortality. This study aims to clarify the frequency and risk factors for tuberculosis in LT recipients. METHODS: A total of 884 LT recipients were investigated retrospectively at China Medical University Hospital, Taichung, Taiwan. We performed a case-control study (1:2) to investigate the potential risk factors and disease onset of TB after LT. RESULTS: Among the 884 LT recipients, 25 of TB cases (2.8%) were reported from 2009 to 2016. The overall incidence of TB was 744 cases per 100,000 patient-year, which was 18-fold higher than the general population in Taiwan. The median time to develop TB after liver transplant was 20 months. Of the TB cases, 15 were pulmonary TB and 10 were extra-pulmonary TB. Five cases of those extra-pulmonary TB occurred in the first post-transplant year. Overall five-year survival rate was 63.3%. Multivariate analyses identified apical fibrotic change in pre-transplant computed tomographic (CT) finding and the exposure to mammalian target of rapamycin (mTOR) inhibitors before TB event as independent risk factors for TB development (Odd ratio (OR) 10.79, 95% confidence interval (CI), 1.73-67.49, p = 0.01; OR 3.847, 95% CI 0.80-18.51, P = 0.09, respectively). CONCLUSION: TB incidence in LT recipients is high in this study. Among those post-transplant recipients with long-term immunosuppression, abnormal CT finding and exposure to mTOR inhibitors before liver transplant might be the risk factors for TB.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31605158

RESUMO

Copper (Cu) bioavailability varies under water conditions. In the present study, the whole life of zebrafish was divided into three different life stages (larvae, juvenile and adult) based on the growth curve, then the influences of water hardness and dissolved organic carbon (DOC) concentration on the acute toxicity of zebrafish were respectively investigated. The results indicated that the life stages had significant effects on Cu toxicity. The larvae stage was less sensitive to Cu than both the juvenile and adult stages. With the increase of water hardness, the toxicity of Cu on zebrafish was decreased, a linear relationship was observed between water hardness and Cu toxicity, and the same was true for DOC concentration. The results showed that taking the 24 days juvenile zebrafish to study the water quality criteria of Cu was stable, sensitive and economical.

4.
J Am Chem Soc ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31657909

RESUMO

Two-dimensional (2D) organic-inorganic perovskites (OIPs), with improved material stability over their 3D counterparts, are highly desirable for device applications. It is their considerable structural diversity that offers an unprecedented opportunity to engineer materials with fine-tuning functionalities. The isosteric substitution of hydrogen by an electronegative fluorine atom has been proposed as a useful route to improve the photovoltaic performance of 2D OIPs, whereas its valuable role in developing ferroelectricity is still waiting for further exploration. Herein, for the first time we applied fluorinated aromatic cations in extending the family of 2D OIP ferroelectrics, and successfully obtained [2-fluorobenzylammonium]2PbCl4 as a high-performance ferroelectric semiconductor. The failures in the nonferroelectric [4-fluorobenzylammonium]2PbCl4 and [3-fluorobenzylammonium]2PbCl4 demonstrate that the selective introduction of fluorine in correct structural positions is particularly essential. This work represents an unprecedented proof-of-concept in the use of fluorinated aromatic cations for the targeted design of excellent 2D OIP ferroelectrics, and is believed to inspire the future development of low-cost, high-efficiency, and stable device applications.

5.
Transl Psychiatry ; 9(1): 260, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624233

RESUMO

Chronic stressful occurrences are documented as a vital cause of both depression and anxiety disorders. However, the stress-induced molecular mechanisms underlying the common and distinct pathophysiology of these disorders remains largely unclear. We utilized a chronic mild stress (CMS) rat model to differentiate and subgroup depression-susceptible, anxiety-susceptible, and insusceptible rats. The hippocampus was analyzed for differential proteomes by combining mass spectrometry and the isobaric tags for relative and absolute quantitation (iTRAQ) labeling technique. Out of 2593 quantified proteins, 367 were aberrantly expressed. These hippocampal protein candidates might be associated with susceptibility to stress-induced depression or anxiety and stress resilience. They provide the potential protein systems involved in various metabolic pathways as novel investigative protein targets. Further, independent immunoblot analysis identified changes in Por, Idh2 and Esd; Glo1, G6pdx, Aldh2, and Dld; Dlat, Ogdhl, Anxal, Tpp2, and Sdha that were specifically associated to depression-susceptible, anxiety-susceptible, or insusceptible groups respectively, suggesting that identical CMS differently impacted the mitochondrial and metabolic processes in the hippocampus. Collectively, the observed alterations to protein abundance profiles of the hippocampus provided significant and novel insights into the stress regulation mechanism in a CMS rat model. This might serve as the molecular basis for further studies that would contributed to a better understanding of the similarities and differences in pathophysiologic mechanisms underlying stress-induced depression or anxiety, and stress resiliency.

7.
Atherosclerosis ; 290: 125-135, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31614249

RESUMO

BACKGROUND AND AIMS: Hyperlipidemia-induced atherosclerosis is the major cause of heart attack and stroke in humans. However, pathological details and molecular mechanisms underlying early atherogenesis remain incompletely characterized. This study explored the early events of atherogenesis in a hypercholesterolemic zebrafish model in vivo. METHODS: We used transparent transgenic zebrafish larvae Tg(lysc:EGFP), Tg(mpx:EGFP), Tg(mpeg1:EGFP), Tg(flk1:EGFP) or Tg(lysc:EGFP/flk1:mCherry), together with fluorescently labeled control and high cholesterol diets (HCD), to dynamically investigate the early development of atherosclerosis with confocal in vivo. Endothelial cells with green fluorescence were sorted by fluorescence-activated cell sorting (FACS) to detect gene expression. Moreover, we treated hypercholesterolemic zebrafish model in vivo or human umbilical vein endothelial cells (HUVEC) in vitro with rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ (PPARγ). RESULTS: We found that HCD-induced endothelial inflammation was an earlier pathological alteration than myeloid cells/neutrophils accumulation and lipid deposition in zebrafish vascular vessels of HCD-fed zebrafish. Endothelial inflammation was characterized by down-regulation of anti-inflammatory PPARγ and upregulation of pro-inflammatory tumor necrosis factor α (TNF-α) and interleukin-1ß (IL-1ß). Pharmacological treatment with rosiglitazone reversed the decrease in the expression of PPARγ and decreased expression of TNF-α and IL-1ß in HCD-fed zebrafish. Moreover, rosiglitazone ameliorated myeloid cells accumulation and lipid deposition in HCD-fed zebrafish in vivo. CONCLUSIONS: Hyperlipidemia-induced endothelial inflammation happens earlier than myeloid cell neutrophils accumulation in vascular vessels, and neutrophils accumulation is prior to lipid deposition during the initial stage of atherosclerosis. Early alleviation of inflammation induced by HCD would have a prophylactic effect for the initial development of atherosclerosis.

9.
Hum Brain Mapp ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571346

RESUMO

Schizophrenia has been conceptualized as a disorder arising from structurally pathological alterations to white-matter fibers in the brain. However, few studies have focused on white-matter functional changes in schizophrenia. Considering that converging evidence suggests that white-matter resting state functional MRI (rsfMRI) signals can effectively depict neuronal activity and psychopathological status, this study examined white-matter network-level interactions in antipsychotic-naive first-episode schizophrenia (FES) to facilitate the interpretation of the psychiatric pathological mechanisms in schizophrenia. We recruited 42 FES patients (FESs) and 38 healthy controls (HCs), all of whom underwent rsfMRI. We identified 11 white-matter functional networks, which could be further classified into deep, middle, and superficial layers of networks. We then examined network-level interactions among these 11 white-matter functional networks using coefficient Granger causality analysis. We employed group comparisons on the influences among 11 networks using network-based statistic. Excitatory influences from the middle superior corona radiate network to the superficial orbitofrontal and deep networks were disrupted in FESs compared with HCs. Additionally, an extra failure of suppression within superficial networks (including the frontoparietal network, temporofrontal network, and the orbitofrontal network) was observed in FESs. We additionally recruited an independent cohort (13 FESs and 13 HCs) from another center to examine the replicability of our findings across centers. Similar replication results further verified the white-matter functional network interaction model of schizophrenia. The novel findings of impaired interactions among white-matter functional networks in schizophrenia indicate that the pathophysiology of schizophrenia may also lie in white-matter functional abnormalities.

10.
Chemistry ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573724

RESUMO

Since the first perovskite CaTiO3 was discovered in 1839s, the development of perovskite has a history of 180 years. The emergence of solar cells-(CH3NH3)PbI3 has set off the trend of hybrid organic-inorganic perovskite (HOIP) materials. Since then, various HOIPs have sprung up and been widely used in various material devices. Among them, HOIP ferroelectrics have gained widespread attention. However, antiperovskite, as a twin brother of perovskite, has been neglected although it has similar structure with perovskite. Here, we successfully found that [C3H7FN]3[SnCl6]Cl (1) has a three-dimensional (3D) antiperovskite structure with the formula M3AB. Importantly, 1 exhibits obvious ferroelectric properties with an Aizu notation of 622F6 at 391 K. To the best of our knowledge, this is the first 3D hybrid organic-inorganic antiperovskite ferroelectric, which will greatly promote the development of antiperovskite families with more superior physical properties.

11.
Chem Asian J ; 14(21): 3863-3867, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31503382

RESUMO

Molecular optical-dielectric duple bistable switches are photoelectric (dielectric and fluorescent) multifunctional materials that can simultaneously convert optical and electrical signals in one device for seamless integration. However, exploring optical-dielectric duple channels of dielectric and photoluminescence is still a bigger challenge than single dielectric or photoluminescence bistable ones, which are hardly reported but probably will be heavily researched owing to the new generation artificial intelligence development needs in the future. Herein, a new optical-dielectric duple bistable switches material, [(CH3 )3 NCH2 CH3 ]2 MnCl4 (I), was obtained by a simple method for volatilization of solvents. Variable temperature single crystal X-ray analysis indicates that material I has a reversible bistable structure (order-disorder structure phase transition) corresponding to switching "ON'' and "OFF''. Unlike the single dielectric bistable structures that were previously reported, material I also own bistable features in terms of fluorescence property. This material enriches the specific examples of photoelectric duple function switch materials and facilitates the development of required devices.

12.
Mol Med Rep ; 20(5): 4393, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31485629

RESUMO

Following the publication of this paper, the authors have realized that the name of their institute, as presented in the affiliations, should have been changed from "Children's Hospital Affiliated to Nanjing Medical University" to "Children's Hospital of Nanjing Medical University". Therefore, the authors' affiliations, and the affliation address, should have appeared as follows: Hui Zhu*, Xinyue Qi*, Yuehe Liu*, Wei Liao, Xiangshui Sun and Yuping Tang. Department of Orthopedics, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China. *Contributed equally. The authors confirm that there are no further errors in the study, and all the authors agree to this correction. The authors regret this error in the affiliations, and apologize for any inconvenience caused. [the original article was published in Molecular Medicine Reports 20: 685­692, 2019; DOI: 10.3892/mmr.2019.10271].

13.
J Environ Manage ; 250: 109539, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31521040

RESUMO

Water quality criteria are the basis for formulating environmental water quality standards, and are also an important part of environmental water protection and environmental management programs. The current study focused on a systematic discussion of the current research progress of water quality criteria theories and methodology for aquatic organisms both in China and internationally. This study also successfully pointed out key scientific issues which should be considered in the determination of water quality criteria guidelines from the following perspectives for a national strategy: the selection of pollutants; data collection and screening; species selection; water quality criteria derivation methods, and so on. For the first time, this study systematically introduced technology for the determination of water quality criteria guidelines for protecting aquatic organisms which was suitable for China's regional characteristics and national conditions. Furthermore, this study pointed out the key research directions which should be considered in the future construction of China's environmental criteria and management systems, in order to provide technical support for environmental protection and management projects.


Assuntos
Poluentes Químicos da Água , Qualidade da Água , Organismos Aquáticos , China , Água Doce
14.
Artigo em Inglês | MEDLINE | ID: mdl-31499585

RESUMO

RATIONALE: Accumulating evidence has linked prolonged exposure to heavy metals to cancer occurrence in the urinary system. However, the specific biological mechanisms responsible for the association of heavy metals with the unusually high incidence of upper tract urothelial carcinoma in Taiwan are complex and incompletely understood. METHODS: To elucidate the specific biological mechanism and identify molecular indicators of the unusually high association of upper tract urothelial carcinoma with heavy metal exposure, protein expression following the treatment of T24 human bladder carcinoma and RT4 human bladder papilloma cell line models with arsenic (As) and cadmium (Cd) were studied. Proteomic changes in these cell models were integrated with data from a human bladder cancer (BLCA) tissue proteome to identify possible protein indicators of heavy metal exposure. RESULTS: After mass spectrometry-based proteomic analysis and verification by Western blotting procedures, we identified 66 proteins that were up-regulated and 92 proteins that were down-regulated in RT4 cell extracts after treatment with As or Cd. 52 proteins were up-regulated and 136 proteins were down-regulated in T24 cell extracts after treatment with Cd. We further confirmed that down-expression of PML (promyelocytic leukemia) protein was sustained for at least 75 days after exposure of bladder cells to As. Dysregulation of these cellular proteins by As were associated with three biological pathways. Immunohistochemical analyses of paraffin-embedded BLCA tissue slides confirmed that PML protein expression was decreased in BLCA tumor cells compared with adjacent noncancerous epithelial cells. CONCLUSIONS: These data suggest that PML may play an important role in the pathogenesis of BLCA and may be an indicator of heavy metal exposure in bladder cells.

15.
Mol Inform ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503423

RESUMO

Organic solar cells are an inexpensive, flexible alternative to traditional silicon-based solar cells but disadvantaged by low power conversion efficiency due to empirical design and complex manufacturing processes. This process can be accelerated by generating a comprehensive set of potential candidates. However, this would require a laborious trial and error method of modeling all possible polymer configurations. A machine learning model has the potential to accelerate the process of screening potential donor candidates by associating structural features of the compound using molecular fingerprints with their highest occupied molecular orbital energies. In this paper, extremely randomized tree learning models are employed for the prediction of HOMO values for donor compounds, and a web application is developed.1 The proposed models outperform neural networks trained on molecular fingerprints as well as SMILES, as well as other state-of-the-art architectures such as Chemception and Molecular Graph Convolution on two datasets of varying sizes.

16.
J Thorac Oncol ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31557536

RESUMO

BACKGROUND: Osimertinib is the current recommended treatment for EGFR T790M-positive NSCLC following EGFR-TKI therapy. However, resistance to osimertinib therapy is inevitably acquired after a period of effective treatment. We had a patient suffering from EGFR L858R/T790M-positive NSCLC who initially responded to osimertinib therapy but eventually developed resistance. Plasma cell-free DNA analysis revealed the occurrence of exon-16-skipping HER2, which may resulted in the HER2 splice variant, HER2D16. HER2D16 has never been reported in lung cancer, and HER2D16-driven signaling was known to be regulated by Src-kinase in breast cancer. We investigated the role of HER2D16 as an osimertinib-resistant mechanism. METHODS: We constructed and established H1975 cells stably expressing HER2D16. The dimeric formation of HER2D16 was tested using non-reducing polyacrylamide gel electrophoresis (PAGE). The effects of drug on signaling transduction were examined using Western blot. The synergistic effect was assessed using Chou-Talalay method. RESULTS: We found HER2D16 can form homo-dimer in NSCLC cells. HER2D16-expressing H1975 cells were resistant to osimertinib treatment. We also found mutant EGFR and HER2D16 cooperated to activate downstream signaling for osimertinib-resistance. Besides, co-treatment with osimertinib and Src-kinase inhibitor failed to reverse resistance, indicating that HER2D16-driven signaling in NSCLC was not through canonical pathway. Finally, we revealed that the combination of osimertinib with the pan-HER small molecular inhibitor, afatinib, could synergistically repress cell growth and signaling in H1975-HER2D16 cells. CONCLUSION: HER2D16 can contribute to osimertinib resistance through Src independent pathway. HER2D16 should be included in the molecular diagnosis panel for lung cancer.

17.
Org Lett ; 21(19): 7692-7696, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31524406

RESUMO

An originally designed Rh-catalyzed [4 + 2] cycloaddition reaction of nitrogen-tethered 1,7-ene-dienes turned out to be a cycloisomerization reaction, which involves allylic C-H activation/alkene insertion into Rh-H bond/reductive elimination processes. Deuterium labeling experiments gave support to the proposed mechanism. This unexpected cycloisomerization reaction provides an efficient way to synthesize trans-divinylpiperidines from easily accessed linear 1,7-ene-dienes.

18.
Brain ; 142(10): 3028-3044, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31435640

RESUMO

GABRB3 is highly expressed early in the developing brain, and its encoded ß3 subunit is critical for GABAA receptor assembly and trafficking as well as stem cell differentiation in embryonic brain. To date, over 400 mutations or variants have been identified in GABRB3. Mutations in GABRB3 have been increasingly recognized as a major cause for severe paediatric epilepsy syndromes such as Lennox-Gastaut syndrome, Dravet syndrome and infantile spasms with intellectual disability as well as relatively mild epilepsy syndromes such as childhood absence epilepsy. There is no plausible molecular pathology for disease phenotypic heterogeneity. Here we used a very high-throughput flow cytometry assay to evaluate the impact of multiple human mutations in GABRB3 on receptor trafficking. In this study we found that surface expression of mutant ß3 subunits is variable. However, it was consistent that surface expression of partnering γ2 subunits was lower when co-expressed with mutant than with wild-type subunits. Because γ2 subunits are critical for synaptic GABAA receptor clustering, this provides an important clue for understanding the pathophysiology of GABRB3 mutations. To validate our findings further, we obtained an in-depth comparison of two novel mutations [GABRB3 (N328D) and GABRB3 (E357K)] associated with epilepsy with different severities of epilepsy phenotype. GABRB3 (N328D) is associated with the relatively severe Lennox-Gastaut syndrome, and GABRB3 (E357K) is associated with the relatively mild juvenile absence epilepsy syndrome. With functional characterizations in both heterologous cells and rodent cortical neurons by patch-clamp recordings, confocal microscopy and immunoblotting, we found that both the GABRB3 (N328D) and GABRB3 (E357K) mutations reduced total subunit expression in neurons but not in HEK293T cells. Both mutant subunits, however, were reduced on the cell surface and in synapses, but the Lennox-Gastaut syndrome mutant ß3 (N328D) subunit was more reduced than the juvenile absence epilepsy mutant ß3 (E357K) subunit. Interestingly, both mutant ß3 subunits impaired postsynaptic clustering of wild-type GABAA receptor γ2 subunits and prevented γ2 subunits from incorporating into GABAA receptors at synapses, although by different cellular mechanisms. Importantly, wild-type γ2 subunits were reduced and less clustered at inhibitory synapses in Gabrb3+/- knockout mice. This suggests that impaired receptor localization to synapses is a common pathophysiological mechanism for GABRB3 mutations, although the extent of impairment may be different among mutant subunits. The study thus identifies the novel mechanism of impaired targeting of receptors containing mutant ß3 subunits and provides critical insights into understanding how GABRB3 mutations produce severe epilepsy syndromes and epilepsy phenotypic heterogeneity.

19.
World Neurosurg ; 131: e402-e407, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31376559

RESUMO

BACKGROUND: Spontaneous intracerebral hemorrhage (SICH) is of high mortality and morbidity. SICH in the basal ganglia is usually attributed to chronic hypertension. Postoperative rehemorrhage is a severe complication, and it is relative to surgical techniques. METHODS: A retrospective survey was conducted on 123 patients with basal ganglia SICH who received surgery from January 2015 to January 2019. Postoperative rehemorrhage within 24 hours was recorded. Preoperative clinical parameters, surgeon experience (<10 and >20 years), operation time, surgical approach, and hemostasis technique were recorded and analyzed. RESULTS: The total postoperative rehemorrhage rate was 12.2% (15/123). The univariable analysis showed general surgeons had a higher postoperative rehemorrhage rate than experienced surgeons (30.4% vs. 8.6%, respectively; P = 0.068). The operation time (minutes) in experienced surgeons was significantly longer (164.9 ± 53.5 vs. 137.7 ± 30.8, P = 0.016), but they had a higher chance to locate the responsible vessel (74.2% vs. 40.0%, P = 0.001), respectively. Logistic analysis indicated that experienced surgeons significantly reduced the risk of rehemorrhage (odds ratio [OR], 0.242; P = 0.021). Transsylvian approach was a protective factor for postoperative rehemorrhage (OR, 0.291; P = 0.045). CONCLUSIONS: Surgeons' experience plays the most important role in postoperative rehemorrhage. Surgeons with rich experience were willing to spend more time to achieve definitive hemostasis in operation. The use of a transsylvian approach can significantly reduce the rehemorrhage rate. Packing hemostasis with gelatin sponge may increase complications.

20.
Mol Psychiatry ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409883

RESUMO

Disturbance of glucose metabolism may be implicated in cognitive deficits of schizophrenia in its early phases. Many studies have reported the important role of widespread disruption of white matter (WM) connectivity in pathogenesis, cognitive deficit and psychopathology of schizophrenia. However, no study has investigated their inter-relationships in drug-naive first episode (DNFE) patients with schizophrenia. Glucose metabolism parameters including fasting glucose, insulin and homeostasis model of assessment-insulin resistance (HOMA-IR) index, cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB) and the voxel-wised WM fractional anisotropy (FA) values were examined using DTI in 39 DNFE schizophrenia and 31 control subjects. The Positive and Negative Syndrome Scale was utilized for clinical symptoms. The patients showed significantly greater fasting plasma levels of glucose and insulin and HOMA-IR, and poorer cognitive scores, together with widespread reduced FA values in five brain areas, including left and right corpus callosum, superior longitudinal fasciculus, posterior thalamic radiation, and corona radiata (all p < 0.05). Association analysis showed that glucose level was positively associated with Digital Sequence Test and Continuous Performance Test, but negatively with FA values in posterior thalamic radiation and left corpus callosum in patients (all p < 0.05). Furthermore, multiple regression analysis revealed that the interactions of glucose × FA in left corpus callosum, longitudinal fasciculus and corona radiata were independent contributors to the Brief Visuospatial Memory Test (BVMT) of MCCB, while the interaction of glucose × FA in left corpus callosum, or in longitudinal fasciculus was associated with MCCB mazes and Trail Making A Test, respectively. Therefore, abnormal glucose metabolism, cognitive impairment and widespread disruption of WM structure occur in an early course of schizophrenia onset. An interaction between glucose metabolism abnormality and the WM dysconnectivity may lead to cognitive impairment.

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