Publications by authors named "Junchao Huang"

70 Publications

Using green alga Haematococcus pluvialis for astaxanthin and lipid co-production: Advances and outlook.

Bioresour Technol 2021 Nov 10;340:125736. Epub 2021 Aug 10.

Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Shenzhen 518060, China; Institute for Innovative Development of Food Industry, Shenzhen University, Shenzhen 518060, China. Electronic address:

Astaxanthin is one of the secondary carotenoids involved in mediating abiotic stress of microalgae. As an important antioxidant and nutraceutical compound, astaxanthin is widely applied in dietary supplements and cosmetic ingredients. However, most astaxanthin in the market is chemically synthesized, which are structurally heterogeneous and inefficient for biological uptake. Astaxanthin refinery from Haematococcus pluvialis is now a growing industrial sector. H. pluvialis can accumulate astaxanthin to ∼5% of dry weight. As productivity is a key metric to evaluate the production feasibility, understanding the biological mechanisms of astaxanthin accumulation is beneficial for further production optimization. In this review, the biosynthesis mechanism of astaxanthin and production strategies are summarized. The current research on enhancing astaxanthin accumulation and the potential joint-production of astaxanthin with lipids was also discussed. It is conceivable that with further improvement on the productivity of astaxanthin and by-products, the algal-derived astaxanthin would be more accessible to low-profit applications.
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http://dx.doi.org/10.1016/j.biortech.2021.125736DOI Listing
November 2021

N-methyl-D-aspartate receptor antibody and the choroid plexus in schizophrenia patients with tardive dyskinesia.

J Psychiatr Res 2021 Oct 13;142:290-298. Epub 2021 Aug 13.

Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, PR China. Electronic address:

Background: Immune disturbance has been postulated to be one of the mechanisms underlying the pathogenesis of tardive dyskinesia (TD). Recently, the role of autoimmune abnormality in TD has been increasingly recognized. Autoantibodies against neuronal N-methyl-D-aspartate receptor (NMDAR) may be cross-reactive in the brain in neuropsychiatric disorders, and the choroid plexus (CP) is a crucial immune barrier in the central nervous system (CNS). We supposed that NMDAR antibodies might underlie the pathophysiological process of TD through the mediation of CP.

Methods: Serum NMDAR antibody levels were assessed by enzyme-linked immunosorbent assay, CP and ventricle volumes were assessed by magnetic resonance imaging in schizophrenia patients with TD (n = 61), without TD (NTD, n = 61), and in healthy controls (n = 74). Psychopathology and TD severity were assessed by the Positive and Negative Syndrome Scale and Abnormal Involuntary Movement Scale (AIMS).

Results: NMDAR antibody levels were significantly higher, CP volumes were larger in the TD group than in the NTD group (p = 0.022; p = 0.019, respectively). In the TD group, higher NMDAR antibody level was correlated with larger CP volume (β = 0.406, p = 0.002). An elevated NMDAR antibody level and enlarged CP volume were correlated with orofacial AIMS score (β = 0.331, p = 0.011; β = 0.459, p = 3.34 × 10, respectively). In a mediation model, the effect of NMDAR antibody level on the orofacial AIMS score was mediated by the CP volume (indirect effect: β = 0.08, 95% confidence interval = 0.002-0.225; direct effect: β = 0.14, p = 0.154).

Conclusions: Our findings highlight a potential NMDAR antibody-associated mechanism in orofacial TD, which may be mediated by increased CP volume.
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http://dx.doi.org/10.1016/j.jpsychires.2021.08.010DOI Listing
October 2021

Hierarchical CNN-based occlusal surface morphology analysis for classifying posterior tooth type using augmented images from 3D dental surface models.

Comput Methods Programs Biomed 2021 Sep 21;208:106295. Epub 2021 Jul 21.

School of Automation, Hangzhou Dianzi University, 310018, Hangzhou, China.

Objective: 3D Digitization of dental model is growing in popularity for dental application. Classification of tooth type from single 3D point cloud model without assist of relative position among teeth is still a challenging task.

Methods: In this paper, 8-class posterior tooth type classification (first premolar, second premolar, first molar, second molar in maxilla and mandible respectively) was investigated by convolutional neural network (CNN)-based occlusal surface morphology analysis. 3D occlusal surface was transformed to depth image for basic CNN-based classification. Considering the logical hierarchy of tooth categories, a hierarchical classification structure was proposed to decompose 8-class classification task into two-stage cascaded classification subtasks. Image augmentations including traditional geometrical transformation and deep convolutional generative adversarial networks (DCGANs) were applied for each subnetworks and cascaded network.

Results: Results indicate that combing traditional and DCGAN-based augmented images to train CNN models can improve classification performance. In the paper, we achieve overall accuracy 91.35%, macro precision 91.49%, macro-recall 91.29%, and macro-F1 0.9139 for the 8-class posterior tooth type classification, which outperform other deep learning models. Meanwhile, Grad-cam results demonstrate that CNN model trained by our augmented images will focus on smaller important region for better generality. And anatomic landmarks of cusp, fossa, and groove work as important regions for cascaded classification model.

Conclusion: The reported work has proved that using basic CNN to construct two-stage hierarchical structure can achieve the best classification performance of posterior tooth type in 3D model without assistance of relative position information. The proposed method has advantages of easy training, great ability to learn discriminative features from small image region.
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http://dx.doi.org/10.1016/j.cmpb.2021.106295DOI Listing
September 2021

The mediating effect of brain-derived neurotrophic factor levels on childhood trauma and psychiatric symptoms in patients with first-episode schizophrenia.

Aust N Z J Psychiatry 2021 Jul 15:48674211031478. Epub 2021 Jul 15.

Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, P.R. China.

Background: Previous studies have implicated childhood trauma and abnormal brain-derived neurotrophic factor in the pathogenesis of schizophrenia. Here, we explored whether brain-derived neurotrophic factor levels mediated the relationship between childhood trauma and psychopathological symptoms in patients with first-episode schizophrenia.

Methods: Patients with first-episode schizophrenia ( = 192) and healthy controls ( = 136) were enrolled. Childhood traumatic experiences and psychopathology were assessed by Childhood Trauma Questionnaire and Positive and Negative Syndrome Scale, respectively. Enzyme-linked immunosorbent assay was used to quantify brain-derived neurotrophic factor levels.

Results: The patients with first-episode schizophrenia experienced more severe childhood trauma and had lower serum brain-derived neurotrophic factor levels than healthy controls. Emotional abuse and Childhood Trauma Questionnaire total score showed positive correlation with Positive and Negative Syndrome Scale positive, general psychopathological subscore and total score. Emotional neglect showed positive correlation with Positive and Negative Syndrome Scale positive subscore. Physical neglect was positively associated with Positive and Negative Syndrome Scale negative subscore. Emotional neglect and Childhood Trauma Questionnaire total score were negatively correlated with serum brain-derived neurotrophic factor levels. The serum brain-derived neurotrophic factor levels mediated the relationship between both Childhood Trauma Questionnaire total score and Positive and Negative Syndrome Scale total score and negative symptoms in the patients. The brain-derived neurotrophic factor levels also mediated the relationship between emotional neglect and Positive and Negative Syndrome Scale total score in the patients.

Conclusion: Childhood trauma might contribute to the clinical symptoms of schizophrenia by affecting brain-derived neurotrophic factor levels. Perhaps we can prevent schizophrenia by reducing childhood traumatic experiences.
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http://dx.doi.org/10.1177/00048674211031478DOI Listing
July 2021

Function and clinical significance of N6-methyladenosine in digestive system tumours.

Exp Hematol Oncol 2021 Jul 10;10(1):40. Epub 2021 Jul 10.

Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, China.

RNA modification, like DNA methylation, histone modification, non-coding RNA modification and chromatin rearrangement, plays an important role in tumours. N6-methyladenosine (m6A) is the most abundant RNA modification in cells, and it regulates RNA transcription, processing, splicing, degradation, and translation. m6A-associated proteins have been used as new biomarkers and therapeutic targets for tumour prediction and monitoring. There are three main types of proteins involved in m6A methylation: methyltransferases (METTL3, METTL14, WTAP, RBM15, ZC3H13 and KIAA1429), demethylases (FTO, ALKBH5 and ALKBH3) and RNA-binding proteins (YTHDF1-3, YTHDC1-2, IGF2BPs and HNRNPs). This article reviews the origins, characteristics and functions of m6A and its relationship with digestive system tumours based on recent research. The expression of m6A regulators can be used as an evaluation indicator of tumour growth and progression and as a prognostic indicator. In-depth research on m6A methylation in digestive system tumours may provide new directions for clinical prediction and further treatment.
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http://dx.doi.org/10.1186/s40164-021-00234-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272376PMC
July 2021

Investigation of the Effects of Electrode Geometry on the Performance of CD Sensor with Radial Configuration.

Sensors (Basel) 2021 Jun 29;21(13). Epub 2021 Jun 29.

State Key Laboratory of Industrial Control Technology, College of Control Science and Engineering, Zhejiang University, Hangzhou 310027, China.

Electrodes are basic components of CD (capacitively coupled contactless conductivity detection) sensors, and different electrode structures (the configuration pattern or the electrode geometry) can lead to different measurement results. In this work, the effects of electrode geometry of radial configuration on the measurement performance of CD sensors are investigated. Two geometrical parameters, the electrode length and the electrode angle, are considered. A FEM (finite element method) model based on the CD method is developed. With the FEM model, corresponding simulation results of conductivity measurement with different electrode geometry are obtained. Meanwhile, practical experiments of conductivity measurement are also conducted. According to the simulation results and experimental results, the optimal electrode geometry of the CD sensor with radial configuration is discussed and proposed. The recommended electrode length is 5-10 times of the pipe inner diameter and the recommended electrode angle is 120-160°.
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http://dx.doi.org/10.3390/s21134454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272098PMC
June 2021

Continuous Pilot-Scale Wet-Spinning of Biocompatible Chitin/Chitosan Multifilaments from an Aqueous KOH/Urea Solution.

Macromol Rapid Commun 2021 Aug 17;42(16):e2100252. Epub 2021 Jun 17.

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei, 430072, P. R. China.

Chitin is a promising natural polymer with great potential as a biomedical, hygiene, absorbent, and food-packing material. Producing chitin multifilament and assembling them into textiles is an efficient way of preparing these materials, with wet-spinning a major method used to produce man-made fibers. Unfortunately, dissolving chitin, producing a stable and suitable chitin dope, and ensuring filament strength are the main obstacles to the production of chitin multifilament. Based on recent research into chitin dissolution, solution properties, and high-strength chitin-based materials, chitin multifilament wet-spinning is no longer only a hypothetical strategy. Here, a pilot-scale wet-spinning method is introduced that overcomes the abovementioned limitations. A stable chitin spinning dope is prepared by dissolution and aging in an aqueous KOH/urea solution. A chitin multifilament is prepared by wet-spinning using a pilot-scale wet-spinning apparatus and aqueous alcohol/salt coagulation. After deacetylation, the chitosan multifilament possesses a dense structure and low crystallinity, but excellent mechanical properties. The chitin/chitosan multifilaments exhibit excellent cytocompatibilities and have promising prospects in biomedical applications. The method developed in this work provides a new approach for the pilot-scale wet-spinning of chitin/chitosan multifilaments.
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http://dx.doi.org/10.1002/marc.202100252DOI Listing
August 2021

Kynurenine metabolism and metabolic syndrome in patients with schizophrenia.

J Psychiatr Res 2021 07 8;139:54-61. Epub 2021 May 8.

Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, 100096, PR China. Electronic address:

Accumulating evidence indicates that a dysregulated kynurenine (KYN) pathway (KP) metabolism may play an important role in the pathogenesis of both schizophrenia and metabolic syndrome (MS). However, the underlying mechanisms remain poorly understood. Here, we aimed to evaluate the potential roles of KP in the pathogenesis of MS in schizophrenia. A total of 160 schizophrenia patients and 70 healthy controls were enrolled in this study. KP metabolites were quantified, and MS scores were calculated, for comparisons between patients and controls. Associations among the indices were explored in both groups. Multiple linear regression analyses were performed to investigate the effects of KP metabolites on MS factors. We observed a significantly higher MS score, lower levels of all KP metabolites, and higher nicotinamide adenine dinucleotide (NAD)/quinolinic acid (QUNA) in patients than in controls (all p < 0.01). Partial correlation analyses revealed that, in the patient group, QUNA and QUNA/KYN correlated positively with MS score (r = 0.24 and 0.27, respectively, both p < 0.025), and NAD/QUNA correlated negatively with MS score (r = -0.25, p = 0.002). Results of multiple regression analyses showed significant QUNA × group interactions in the model representing QUNA effects on MS score (β = 0.25) and a significant QUNA/KYN × group interaction in the model representing QUNA/KYN effects on MS score (β = 0.23) (both p < 0.001). Among all factors contributing to MS in schizophrenia, an interactive effect of schizophrenia itself and dysregulated KP plays a contributory role. Conceivably, modulation of the KP could theoretically lead to treating schizophrenia and MS simultaneously.
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http://dx.doi.org/10.1016/j.jpsychires.2021.05.004DOI Listing
July 2021

Effects of neuroactive metabolites of the tryptophan pathway on working memory and cortical thickness in schizophrenia.

Transl Psychiatry 2021 04 1;11(1):198. Epub 2021 Apr 1.

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.

A number of tryptophan metabolites known to be neuroactive have been examined for their potential associations with cognitive deficits in schizophrenia. Among these metabolites, kynurenic acid (KYNA), 5-hydroxyindole (5-HI), and quinolinic acid (QUIN) are documented in their diverse effects on α-7 nicotinic acetylcholine receptor (α7nAChR) and/or N-methyl-D-aspartate receptor (NMDAR), two of the receptor types thought to contribute to cognitive impairment in schizophrenia. In this study, serum levels of KYNA, 5-HI, and QUIN were measured in 195 patients with schizophrenia and in 70 healthy controls using liquid chromatography-tandem mass spectrometry; cognitive performance in MATRICS Consensus Cognitive Battery and cortical thickness measured by magnetic resonance imaging were obtained. Patients with schizophrenia had significantly lower serum KYNA (p < 0.001) and QUIN (p = 0.02) levels, and increased 5-HI/KYNA (p < 0.001) and QUIN/KYNA ratios (p < 0.001) compared with healthy controls. Multiple linear regression showed that working memory was positively correlated with serum 5-HI levels (t = 2.10, p = 0.04), but inversely correlated with KYNA concentrations (t = -2.01, p = 0.05) in patients. Patients with high 5-HI and low KYNA had better working memory than other subgroups (p = 0.01). Higher 5-HI levels were associated with thicker left lateral orbitofrontal cortex (t = 3.71, p = 2.94 × 10) in patients. The different effects of 5-HI and KYNA on working memory may appear consistent with their opposite receptor level mechanisms. Our findings appear to provide a new insight into the dynamic roles of tryptophan pathway metabolites on cognition, which may benefit novel therapeutic development that targets cognitive impairment in schizophrenia.
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http://dx.doi.org/10.1038/s41398-021-01311-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016899PMC
April 2021

Characterization of an algal phosphomannose isomerase gene and its application as a selectable marker for genetic manipulation of tomato.

Plant Divers 2021 Feb 15;43(1):63-70. Epub 2020 Jun 15.

Key Laboratory of Economic Plants and Biotechnology, Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China.

Establishing a transgenic plant largely relies on a selectable marker gene that can confer antibiotic or herbicide resistance to plant cells. The existence of such selectable marker genes in genetically modified foods has long been criticized. Plant cells generally exhibit too low an activity of phosphomannose isomerase (PMI) to grow with mannose as a sole carbon source. In this study, we characterized from the green microalga sp. and assessed its feasibility as a selectable marker for plant biotechnology. sp. () was shown to be closely related to higher plants but more distant to bacterial counterparts. Overexpression of in tomato induced callus and shoot formation in media containing mannose (6 g/L) and had an average transformation rate of 3.9%. Based on this transformation system, a polycistronic gene cluster containing , , and () was co-expressed in a different tomato cultivar. Six putative transformants were achieved with a transformation rate of 1.4%, which produced significant amounts of astaxanthin due to the expression of the genes. Taken together, these findings indicate that we have established an additional tool for plant biotechnology that may be suitable for genetically modifying foods safely.
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http://dx.doi.org/10.1016/j.pld.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987571PMC
February 2021

Effects of microRNA-181b-5p on cognitive deficits in first-episode patients with schizophrenia: Mediated by BCL-2.

J Psychiatr Res 2021 04 14;136:358-365. Epub 2021 Feb 14.

Institute of Biomedicine and Translational Medicine, Department of Physiology, Faculty of Medicine, University of Tartu, Tartu, Estonia.

MicroRNA (miR)-181b-5p is considered to be involved in the pathogenesis of schizophrenia, and one of its regulatory target genes BCL-2 (B-cell lymphoma 2) is suggested to associate with cognition of schizophrenia. Cognitive deficit is a core trait of schizophrenia. However, it remains unclear whether miR-181b-5p affects cognition and its possible pathway in schizophrenia. We hypothesized that miR-181b-5p affects cognition by targeting BCL-2 mRNA and downregulating BCL-2 protein expression in schizophrenia patients. In this study, first-episode patients with schizophrenia (FEPS, n = 123) and age- and gender-matched healthy controls (HCs, n = 50) were enrolled in Chinese populations. Expression levels of miR-181b-5p and BCL-2 mRNA in peripheral whole blood were measured with quantitative real-time PCR (Q-PCR) and BCL-2 protein in plasma were measured with Enzyme Linked Immunosorbent Assay (ELISA). Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS), cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Peripheral blood miR-181b-5p expression level was significantly upregulated (p = 0.001) whereas BCL-2 mRNA and BCL-2 protein levels were significantly downregulated (p = 0.002, p = 0.023 respectively) in the FEPS compared with those in the HCs. The miR-181b-5p level was negatively (p = 0.005), whereas the BCL-2 mRNA level was positively (p < 0.001), correlated with working memory in FEPS. Mediating effect analysis showed that the effect of miR-181b-5p on working memory in the FEPS was exerted via targeting BCL-2 mRNA. MiR-181b-5p in combination with BCL-2 mRNA might be suggested as potential biomarker for schizophrenia in our discovery sample. In conclusion, overexpressed miR-181b-5p may affect cognitive function in patients with schizophrenia.
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http://dx.doi.org/10.1016/j.jpsychires.2021.02.003DOI Listing
April 2021

The microRNA-195 - BDNF pathway and cognitive deficits in schizophrenia patients with minimal antipsychotic medication exposure.

Transl Psychiatry 2021 02 8;11(1):117. Epub 2021 Feb 8.

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.

Cognitive impairment is a core characteristic of schizophrenia, but its underlying neural mechanisms remain poorly understood. Reduced brain-derived neurotrophic factor (BDNF), a protein critical for neural plasticity and synaptic signaling, is one of the few molecules consistently associated with cognitive deficits in schizophrenia although the etiological pathway leading to BDNF reduction in schizophrenia is unclear. We examined microRNA-195 (miR-195), a known modulator of BDNF protein expression, as a potential mechanistic component. One-hundred and eighteen first-episode patients with schizophrenia either antipsychotic medication-naïve or within two weeks of antipsychotic medication exposure and forty-seven age- and sex-matched healthy controls were enrolled. MiR-195 and BDNF mRNA and BDNF protein levels in peripheral blood were tested. Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB). MiR-195 was significantly higher (p = 0.01) whereas BDNF mRNA (p < 0.001) and protein (p = 0.016) levels were significantly lower in patients compared with controls. Higher miR-195 expression was significantly correlated to lower BDNF protein levels in patients (partial r = -0.28, p = 0.003) and lower BDNF protein levels were significantly associated with poorer overall cognitive performance by MCCB and also in speed of processing, working memory, and attention/vigilance domains composite score (p = 0.002-0.004). The subgroup of patients with high miR-195 and low BDNF protein showed the lowest level of cognitive functions, and miR-195 showed significant mediation effects on cognitive functions through BDNF protein. Elevated miR-195 may play a role in regulating BDNF protein expression thereby influencing cognitive impairments in schizophrenia, suggesting that development of cognition enhancing treatment for schizophrenia may consider a micro-RNA based strategy.
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http://dx.doi.org/10.1038/s41398-021-01240-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870897PMC
February 2021

N-methyl-D-aspartate Receptor Antibody and White Matter Deficits in Schizophrenia Treatment-Resistance.

Schizophr Bull 2021 Aug;47(5):1463-1472

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.

Insufficient or lack of response to antipsychotic medications in some patients with schizophrenia is a major challenge in psychiatry, but the underlying mechanisms remain unclear. Two seemingly unrelated observations, cerebral white matter and N-methyl-D-aspartate receptor (NMDAR) hypofunction, have been linked to treatment-resistant schizophrenia (TRS). As NMDARs are critical to axonal myelination and signal transduction, we hypothesized that NMDAR antibody (Ab), when present in schizophrenia, may impair NMDAR functions and white matter microstructures, contributing to TRS. In this study, 50 patients with TRS, 45 patients with nontreatment-resistant schizophrenia (NTRS), 53 patients with schizophrenia at treatment initiation schizophrenia (TIS), and 90 healthy controls were enrolled. Serum NMDAR Ab levels and white matter diffusion tensor imaging fractional anisotropy (FA) were assessed. The white matter specificity effects by NMDAR Ab were assessed by comparing with effects on cortical and subcortical gray matter. Serum NMDAR Ab levels of the TRS were significantly higher than those of the NTRS (P = .035). In patients with TRS, higher NMDAR Ab levels were significantly associated with reduced whole-brain average FA (r = -.37; P = .026), with the strongest effect at the genu of corpus callosum (r = -.50; P = .0021, significant after correction for multiple comparisons). Conversely, there was no significant correlation between whole-brain or regional cortical thickness or any subcortical gray matter structural volume and NMDAR Ab levels in TRS. Our finding highlights a potential NMDAR mechanism on white matter microstructure impairment in schizophrenia that may contribute to their treatment resistance to antipsychotic medications.
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http://dx.doi.org/10.1093/schbul/sbab003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379535PMC
August 2021

Allostatic Load Effects on Cortical and Cognitive Deficits in Essentially Normotensive, Normoweight Patients with Schizophrenia.

Schizophr Bull 2021 07;47(4):1048-1057

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD.

Reduced cortical gray matter integrity and cognitive abilities are among core deficits in schizophrenia. We hypothesized that higher allostatic load (AL) that accounts for exposure to chronic stress is a contributor to structural and cognitive deficits in schizophrenia. One hundred and sixty-seven schizophrenia patients who were on average with normal weight, normal systolic, and diastolic blood pressure and 72 healthy controls were enrolled in the study. Group differences in subclinical cardiovascular, metabolic, immune, and neuroendocrine biological markers as indexed by AL and contribution of AL components to the structural and cognitive deficits in schizophrenia were explored. Compared with controls, schizophrenia patients who were normotensive, normoweight, and had low total cholesterol levels still had significantly higher AL mainly due to lower high-density lipoprotein cholesterol and higher heart rate, waist-hip ratio, hemoglobinA1c, hypersensitive C-reactive protein, and overnight-urine cortisol levels. Patients also had decreased whole-brain mean cortical thickness, and lower cognition assessed by the MATRICS consensus cognitive battery. AL was inversely correlated with mean cortical thickness and cognition in schizophrenia, while none of these relationships existed in controls. Mediation analyses showed the effect of AL on cognitive deficits in schizophrenia was significantly mediated by cortical thinning, and the most significant mediating cortical area was the left superior frontal gyrus. Cortical thickness may act as a mediator between AL and cognitive deficits in schizophrenia. Early intervention strategies to reduce cortical thinning and cognitive dysfunction in schizophrenia should target specific aspects of their high AL in addition to weight gain, hypertension and high cholesterol levels.
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http://dx.doi.org/10.1093/schbul/sbaa196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266595PMC
July 2021

Direct Observation of β-Barrel Intermediates in the Self-Assembly of Toxic SOD1 and Absence in Nontoxic Glycine Mutants.

J Chem Inf Model 2021 02 14;61(2):966-975. Epub 2021 Jan 14.

Department of Physics and Astronomy, Clemson University, Clemson, South Carolina 29634, United States.

Soluble low-molecular-weight oligomers formed during the early stage of amyloid aggregation are considered the major toxic species in amyloidosis. The structure-function relationship between oligomeric assemblies and the cytotoxicity in amyloid diseases are still elusive due to the heterogeneous and transient nature of these aggregation intermediates. To uncover the structural characteristics of toxic oligomeric intermediates, we compared the self-assembly dynamics and structures of SOD1, a cytotoxic fragment of the superoxide dismutase 1 (SOD1) associated with the amyotrophic lateral sclerosis, with its two nontoxic mutants G33V and G33W using molecular dynamics simulations. Single-point glycine substitutions in SOD1 have been reported to abolish the amyloid toxicity. Our simulation results showed that the toxic SOD1 and its nontoxic mutants followed different aggregation pathways featuring distinct aggregation intermediates. Specifically, wild-type SOD1 initially self-assembled into random-coil-rich oligomers, among which fibrillar aggregates composed of well-defined curved single-layer β-sheets were nucleated via coil-to-sheet conversions and the formation of β-barrels as intermediates. In contrast, the nontoxic G33V/G33W mutants readily assembled into small β-sheet-rich oligomers and then coagulated with each other into cross-β fibrils formed by two-layer β-sheets without forming β-barrels as the intermediates. The direct observation of β-barrel oligomers during the assembly of toxic SOD1 fragments but not the nontoxic glycine-substitution mutants strongly supports β-barrels as the toxic oligomers in amyloidosis, probably via interactions with the cell membrane and forming amyloid pores. With well-defined structures, the β-barrel might serve as a novel therapeutic target against amyloid-related diseases.
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http://dx.doi.org/10.1021/acs.jcim.0c01319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902411PMC
February 2021

Single transition metal anchored CN sheets as an efficient catalyst for CO oxidation: a first-principles study.

Phys Chem Chem Phys 2021 Jan;23(3):1868-1873

School of Physical Science and Technology, Ningbo University, Ningbo, P. R. China.

Single-atom catalysts (SACs) often exhibit superb catalytic activity due to their high atom utilization. By comparing the adsorption energies of O2 and CO adsorbed on [email protected], we expect that Co and Ni anchored at the cavity of C9N4 exhibit a higher catalytic activity for CO oxidation. For the entire reaction, the Eley-Rideal, New Eley-Rideal, Ter-molecular Eley-Rideal and Langmuir-Hinshelwood mechanisms are all taken into account. Depending on the reaction mechanisms, the catalysts [email protected] and [email protected] show excellent activity, with a kinetic energy barrier ranging from 0.19 eV to 0.54 eV for the former, while the corresponding energy barrier is 0.26 eV to 0.44 eV for the latter. The superior stability and activity of Co/[email protected] can efficiently oxidize the large amounts of CO caused by inadequate combustion of coal and natural gas resources.
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http://dx.doi.org/10.1039/d0cp05306fDOI Listing
January 2021

CircNEIL3 promotes cervical cancer cell proliferation by adsorbing miR-137 and upregulating KLF12.

Cancer Cell Int 2021 Jan 7;21(1):34. Epub 2021 Jan 7.

Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, China.

Background: CircRNAs play crucial roles in multiple tumours. However, the functions of most circRNAs in cervical cancer remain unclear.

Methods: This study collected GSE113696 data from the GEO database to search for differentially expressed circRNAs in cervical cancer. Quantitative reverse transcription PCR was used to detect the expression level of circNEIL3 in cervical cancer cells and tissues. Then, functional experiments in vitro and in vivo were performed to evaluate the effects of circNEIL3 in cervical cancer.

Results: CircNEIL3 was highly expressed in cervical cancer. In vivo and in vitro experiments verified that circNEIL3 enhanced the proliferation capacity of cervical cancer cells. RNA immunoprecipitation, luciferase reporter assay, pull-down assay, and fluorescent in situ hybridization confirmed the interaction between circNEIL3 and miR-137 in cervical cancer. A luciferase reporter assay showed that circNEIL3 adsorbed miR-137 and upregulated KLF12 to regulate the proliferation of cervical cancer cells.

Conclusions: CircNEIL3 is an oncogene in cervical cancer and might serve as a ceRNA that competitively binds to miR-137, thereby indirectly upregulating the expression of KLF12 and promoting the proliferation of cervical cancer cells.
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http://dx.doi.org/10.1186/s12935-020-01736-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792354PMC
January 2021

Genome-wide DNA methylation analysis of peripheral blood cells derived from patients with first-episode schizophrenia in the Chinese Han population.

Mol Psychiatry 2020 Dec 5. Epub 2020 Dec 5.

Department of Biostatistics and Computational Biology, School of Life Sciences, Fudan University, Shanghai, 200438, PR China.

Schizophrenia is a severe neuropsychiatric disorder with core features including hallucinations, delusions, and cognition deficits. Accumulating evidence has implicated abnormal DNA methylation in the development of schizophrenia. However, the mechanisms by which DNA methylation changes alter the risk for schizophrenia remain largely unknown. We recently carried out a DNA methylome study of peripheral blood samples from 469 first-episode patients with schizophrenia and 476 age- and gender-matched healthy controls of Han Chinese origin. Genomic DNA methylation patterns were quantified using an Illumina Infinium Human MethylationEPIC BeadChip. We identified multiple differentially methylated positions (DMPs) and regions between patients and controls. The most significant DMPs were annotated to genes C17orf53, THAP1 and KCNQ4 (K7.4), with Bonferroni-adjusted P values of [Formula: see text], [Formula: see text], and [Formula: see text], respectively. In particular, KCNQ4 encodes a voltage-gated potassium channel of the K7 family, which is linked to neuronal excitability. The genes associated with top-ranked DMPs also included many genes involved in nervous system development, such as LIMK2 and TMOD2. Gene ontology analysis of the differentially methylated genes further identified strong enrichment of neuronal networks, including neuron projection extension, axonogenesis and neuron apoptotic process. Finally, we provided evidence that schizophrenia-associated epigenetic alterations co-localize with genetic susceptibility loci. By focusing on first-episode schizophrenia patients, our investigation lends particularly strong support for an important role of DNA methylation in schizophrenia pathogenesis unconfounded by the effects of long-term antipsychotic medication or disease progression. The observed DNA methylation aberrations in schizophrenia patients could potentially provide a valuable resource for identifying diagnostic biomarkers and developing novel therapeutic targets to benefit schizophrenia patients.
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http://dx.doi.org/10.1038/s41380-020-00968-0DOI Listing
December 2020

Abnormal functional connectivity of motor circuit in the schizophrenic patients with tardive dyskinesia: A resting-state fMRI study.

Neurosci Lett 2021 01 3;742:135548. Epub 2020 Dec 3.

Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, PR China. Electronic address:

Background: Animal and neuroimaging studies suggest that the volume of the motor-circuit region decreases in tardive dyskinesia (TD). This study examined the differences in functional connectivity within the motor circuit of patients with schizophrenia with and without TD to further clarify how the dysfunction is related to the pathogenesis of TD.

Methods: Functional magnetic resonance images were taken of 56 schizophrenic patients with TD (TD group), 64 without TD (non-TD group), and 68 healthy controls (HC group). The motor-circuit area was selected as the seed region for a whole brain resting-state functional connectivity (rsFC) analysis. Psychopathological symptoms and TD severity were assessed with the Positive and Negative Syndrome Scale (PANSS) and Abnormal Involuntary Movement Scale (AIMS), respectively. Group differences and correlations among 18 brain regions of interest (e.g., the global strength of connectivity between two regions) were analyzed.

Results: The analysis of variance results were as follows: The three groups exhibited rsFC losses in the left primary motor cortex, bilateral parietal cortices, right postcentral gyrus, right putamen, right superior parietal lobule, right supplementary motor area and bilateral thalami (false discovery rate,p < 0.05). The TD group showed a significant rsFC loss between the right postcentral gyrus and the inferior frontal gyrus of the left triangular part when compared with the non-TD group (AlphaSim, p < 0.001), which was negatively correlated with the AIMS total score (r=-0.259, p = 0.03).

Conclusions: These findings may suggest dysfunction of the postcentral and inferior frontal gyri of the triangular part in patients with schizophrenia and TD.
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http://dx.doi.org/10.1016/j.neulet.2020.135548DOI Listing
January 2021

Functional disconnection between subsystems of the default mode network in schizophrenia.

Psychol Med 2020 Nov 13:1-11. Epub 2020 Nov 13.

Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing100096, China.

Background: A dysfunctional default mode network (DMN) has been reported in patients with schizophrenia. However, the stability of the deficits has not been determined across different stages of the disorder.

Methods: We examined the functional connectivity of the DMN subsystems of 125 patients with first-episode schizophrenia (FES) or recurrent schizophrenia (RES), compared to that of 82 healthy controls. We tested the robustness of the findings in an independent cohort of 158 patients and 39 healthy controls. We performed resting-state functional connectivity analysis, and examined the strength of the connections within and between the three subsystems of the DMN (core, dorsal medial prefrontal cortex [dMPFC], and medial temporal lobe [MTL]). We also analyzed the connectivity correlations to symptoms and illness duration.

Results: We found reduced connectivity strength between the core and MTL subsystems in schizophrenia patients compared to controls, with no differences between the FES and RES patient groups; these findings were validated in the second sample. Schizophrenia patients also showed a significant reduction in connectivity within the MTL and between the dMPFC-MTL subsystems, similarly between FES and RES groups. The connectivity strength within the core subsystem was negatively correlated with clinical symptoms in schizophrenia. There was no significant correlation between the DMN subsystem connectivity and illness duration.

Conclusions: DMN subsystem connectivity deficits are present in schizophrenia, and the homochronicity of their appearance indicates the trait-like nature of these alterations. The DMN deficit may be useful for early diagnosis, and MTL dysfunction may be a crucial mechanism underlying schizophrenia.
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http://dx.doi.org/10.1017/S003329172000416XDOI Listing
November 2020

Immature defense mechanisms mediate the relationship between childhood trauma and onset of bipolar disorder.

J Affect Disord 2021 01 15;278:672-677. Epub 2020 Oct 15.

Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, PR China. Electronic address:

Background: Accumulating evidence has converged to suggest that childhood trauma may contribute to bipolar disorder (BD). This study aimed to investigate the patterns of childhood trauma among patients with bipolar I (BD-I) and bipolar II (BD-II) disorders, according to DSM-IV and in contrast with healthy volunteers. We also explored whether the relationship between childhood trauma and onset of bipolar disorder is mediated by immature defense mechanisms.

Methods: Participants were patients with BD-I (n=44) and BD-II (n = 42), and healthy controls (HCs, n = 43). Childhood traumatic experiences and defense mechanisms were assessed by the Childhood Trauma Questionnaire (CTQ) and the Defense Style Questionnaire (DSQ), respectively.

Results: BD patients experienced more severe childhood trauma than HCs. Physical neglect sub-score and total score of the CTQ had both direct and indirect effects on the diagnosis of BD-I, and an immature defense style mediated the indirect effects. The diagnosis of BD-II was mainly related to the physical neglect and emotional abuse subs-core and total score of the CTQ, as mediated by the immature defense mechanisms. BD-I and BD-II significantly differed in the emotional abuse sub-score of the CTQ.

Conclusions: Physical neglect sub-score and total score of the CTQ were associated with the diagnosis of BD (both BD-I and BD-II), as mediated by an immature defense style. Furthermore, emotional abuse might be an important risk factor for BD-II compared to BD-I. These findings may inform risk reduction and psychosocial intervention strategies to prevent and treat patients with bipolar disorders.
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http://dx.doi.org/10.1016/j.jad.2020.10.029DOI Listing
January 2021

Immature defense mechanisms mediate the relationship between childhood trauma and onset of bipolar disorder.

J Affect Disord 2021 01 15;278:672-677. Epub 2020 Oct 15.

Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, PR China. Electronic address:

Background: Accumulating evidence has converged to suggest that childhood trauma may contribute to bipolar disorder (BD). This study aimed to investigate the patterns of childhood trauma among patients with bipolar I (BD-I) and bipolar II (BD-II) disorders, according to DSM-IV and in contrast with healthy volunteers. We also explored whether the relationship between childhood trauma and onset of bipolar disorder is mediated by immature defense mechanisms.

Methods: Participants were patients with BD-I (n=44) and BD-II (n = 42), and healthy controls (HCs, n = 43). Childhood traumatic experiences and defense mechanisms were assessed by the Childhood Trauma Questionnaire (CTQ) and the Defense Style Questionnaire (DSQ), respectively.

Results: BD patients experienced more severe childhood trauma than HCs. Physical neglect sub-score and total score of the CTQ had both direct and indirect effects on the diagnosis of BD-I, and an immature defense style mediated the indirect effects. The diagnosis of BD-II was mainly related to the physical neglect and emotional abuse subs-core and total score of the CTQ, as mediated by the immature defense mechanisms. BD-I and BD-II significantly differed in the emotional abuse sub-score of the CTQ.

Conclusions: Physical neglect sub-score and total score of the CTQ were associated with the diagnosis of BD (both BD-I and BD-II), as mediated by an immature defense style. Furthermore, emotional abuse might be an important risk factor for BD-II compared to BD-I. These findings may inform risk reduction and psychosocial intervention strategies to prevent and treat patients with bipolar disorders.
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http://dx.doi.org/10.1016/j.jad.2020.10.029DOI Listing
January 2021

Chitin-Based Double-Network Hydrogel as Potential Superficial Soft-Tissue-Repairing Materials.

Biomacromolecules 2020 10 27;21(10):4220-4230. Epub 2020 Sep 27.

Laboratory of Soft and Wet Matter, Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810, Japan.

Chitin is a biopolymer, which has been proven to be a biomedical material candidate, yet the weak mechanical properties seriously limit their potentials. In this work, a chitin-based double-network (DN) hydrogel has been designed as a potential superficial repairing material. The hydrogel was synthesized through a double-network (DN) strategy composing hybrid regenerated chitin nanofiber (RCN)-poly (ethylene glycol diglycidyl ether) (PEGDE) as the first network and polyacrylamide (PAAm) as the second network. The hybrid RCN-PEGDE/PAAm DN hydrogel was strong and tough, possessing Young's modulus (elasticity) 0.097 ± 0.020 MPa, fracture stress σ 0.449 ± 0.025 MPa, and work of fracture 5.75 ± 0.35 MJ·m. The obtained DN hydrogel was strong enough for surgical requirements in the usage of soft tissue scaffolds. In addition, chitin endowed the DN hydrogel with good bacterial resistance and accelerated fibroblast proliferation, which increased the NIH3T3 cell number by nearly five times within 3 days. Subcutaneous implantation studies showed that the DN hydrogel did not induce inflammation after 4 weeks, suggesting a good biosafety in vivo. These results indicated that the hybrid RCN-PEGDE/PAAm DN hydrogel had great prospect as a rapid soft-tissue-repairing material.
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http://dx.doi.org/10.1021/acs.biomac.0c01003DOI Listing
October 2020

New method for bubble/slug velocity measurement in small channels.

Rev Sci Instrum 2020 May;91(5):055001

State Key Laboratory of Industrial Control Technology, College of Control Science and Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China.

Based on the CD technique and cross correlation velocity measurement technique, a new method for bubble/slug velocity measurement of the gas-liquid two-phase flow in small channels is proposed. A new CD sensor, which is suitable for the parameter measurement of the gas-liquid two-phase flow in small channels, is developed by introducing the principle of capacitive reactance elimination. With two new CD sensors, a bubble/slug velocity measurement system is developed, and the bubble/slug velocity is determined by the cross correlation velocity measurement technique. To verify the effectiveness of the proposed bubble/slug velocity measurement method, three prototypes of bubble/slug velocity measurement systems with different diameters (1.82 mm, 2.65 mm, and 2.96 mm, respectively) were established, and the bubble/slug measurement experiments were carried out. The research results show that the capacitive reactance elimination is an effective way to overcome the unfavorable influence of the coupled capacitances on measurement results. The experimental results indicate that the proposed method can successfully realize the bubble/slug velocity measurement in small channels, and the velocity measurement accuracy is satisfactory. For the three prototypes of the bubble/slug velocity measurement system, the maximum relative errors of the bubble/slug velocity measurement are all less than 5%.
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http://dx.doi.org/10.1063/1.5134548DOI Listing
May 2020

Translating ENIGMA schizophrenia findings using the regional vulnerability index: Association with cognition, symptoms, and disease trajectory.

Hum Brain Mapp 2020 May 28. Epub 2020 May 28.

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Patients with schizophrenia have patterns of brain deficits including reduced cortical thickness, subcortical gray matter volumes, and cerebral white matter integrity. We proposed the regional vulnerability index (RVI) to translate the results of Enhancing Neuro Imaging Genetics Meta-Analysis studies to the individual level. We calculated RVIs for cortical, subcortical, and white matter measurements and a multimodality RVI. We evaluated RVI as a measure sensitive to schizophrenia-specific neuroanatomical deficits and symptoms and studied the timeline of deficit formations in: early (≤5 years since diagnosis, N = 45, age = 28.8 ± 8.5); intermediate (6-20 years, N = 30, age 43.3 ± 8.6); and chronic (21+ years, N = 44, age = 52.5 ± 5.2) patients and healthy controls (N = 76, age = 38.6 ± 12.4). All RVIs were significantly elevated in patients compared to controls, with the multimodal RVI showing the largest effect size, followed by cortical, white matter and subcortical RVIs (d = 1.57, 1.23, 1.09, and 0.61, all p < 10 ). Multimodal RVI was significantly correlated with multiple cognitive variables including measures of visual learning, working memory and the total score of the MATRICS consensus cognitive battery, and with negative symptoms. The multimodality and white matter RVIs were significantly elevated in the intermediate and chronic versus early diagnosis group, consistent with ongoing progression. Cortical RVI was stable in the three disease-duration groups, suggesting neurodevelopmental origins of cortical deficits. In summary, neuroanatomical deficits in schizophrenia affect the entire brain; the heterochronicity of their appearance indicates both the neurodevelopmental and progressive nature of this illness. These deficit patterns may be useful for early diagnosis and as quantitative targets for more effective treatment strategies aiming to alter these neuroanatomical deficit patterns.
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http://dx.doi.org/10.1002/hbm.25045DOI Listing
May 2020

Mechanical robustness of monolayer nanoparticle-covered liquid marbles.

Soft Matter 2020 May 6;16(19):4632-4639. Epub 2020 May 6.

School of Physical Science and Technology, Shaanxi Key Laboratory of Condensed Matter Structures and Properties, Northwestern Polytechnical University, Xi'an, 710129, China.

Powder-derived liquid marbles (LMs) are versatile nonwetting systems but are confronted with many limitations in application, as their surface particles are usually large and agglomerated. Recently, sol-gel film-derived LMs have come on the scene that are termed monolayer nanoparticle-covered (mNPc) LMs based on their unique characteristics, revealing great application potential but also generating many questions. Here, mechanical robustness, a very important yet to be addressed property, of mNPc LMs was systematically studied. Rolling, pendant contact, and compression experiments were designed using bare and coated glasses with water contact angles (WCAs) ranging from 23° to 157°. With rupture as a quality criteria, the mechanical robustness of mNPc LMs enhanced with the hydrophobicity of solid surfaces that exerted pressure on them, but maintained much weaker than typical powder LMs until the solid surface was superhydrophobic. In particular, when contacting hydrophilic surfaces of WCAs ≤53°, an mNPc LM did not have the capacity for nonwetting and ruptured immediately, even if the pressure approached zero. This was distinct from powder LMs and indicated that a particle shell as thin as ∼20 nm could not prevent intermolecular attractions between the internal liquid and external solid surface. An interface scenario consisting of solid surface microroughness was proposed to address this issue. On the other hand, mNPc LMs remained unruptured on superhydrophobic surfaces but presented degraded elasticity under extreme compression. Uncovering these properties could be of much help for developments of mNPc LMs and their counterparts, the mNPc liquid plasticines.
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http://dx.doi.org/10.1039/d0sm00496kDOI Listing
May 2020

Liquid marbles from soot films.

Soft Matter 2020 May 30;16(18):4512-4519. Epub 2020 Apr 30.

School of Physics Science and Technology, Shaanxi Key Laboratory of Condensed Matter Structures and Properties, Northwestern Polytechnical University, Xi'an 710129, China.

Soot films are the most easily available superhydrophobic surfaces. However, their cohesive forces are very weak such that they have been considered not suitable for direct use. Here we show that the seemingly undesirable mechanical weakness is actually an important property which allows a soot film to work as a superhydrophobic platform and tool, producing liquid marbles with fascinating properties and performances. A soot film is weak enough to lose component carbon nanoparticles (CNPs) on contact with water, but can adhere to a substrate stably on overturning or shaking the substrate. On this basis, we demonstrate that a liquid marble consisting of a liquid core and a CNP shell can be obtained by either rolling or an imprinting process. In addition, it is found that large-volume liquid puddles are easy to produce and manipulate with soot films by arbitrary shaking and pouring operations, without worrying about particles flying off that would occur in conventional powder-based liquid puddle production. The multifunctionality of CNPs endows soot liquid marbles/puddles with great potential in light shielding, electrical conduction, etc. This study reveals a direct application of soot films' superhydrophobicity, provides an alternative route for liquid marble production, and highlights the concept of disadvantage reversion.
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http://dx.doi.org/10.1039/c9sm02199jDOI Listing
May 2020

Pyrosequencing analysis of IRS1 methylation levels in schizophrenia with tardive dyskinesia.

Mol Med Rep 2020 Apr 12;21(4):1702-1708. Epub 2020 Feb 12.

Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, P.R. China.

Tardive dyskinesia (TD) is a serious side effect of certain antipsychotic medications that are used to treat schizophrenia (SCZ) and other mental illnesses. The methylation status of the insulin receptor substrate 1 (IRS1) gene is reportedly associated with SCZ; however, no study, to the best of the authors' knowledge, has focused on the quantitative DNA methylation levels of the IRS1 gene using pyrosequencing in SCZ with or without TD. The present study aimed to quantify DNA methylation levels of 4 CpG sites in the IRS1 gene using a Chinese sample including SCZ patients with TD and without TD (NTD) and healthy controls (HCs). The general linear model (GLM) was used to detect DNA methylation levels among the 3 proposed groups (TD vs. NTD vs. HC). Mean DNA methylation levels of 4 CpG sites demonstrated normal distribution. Pearson's correlation analysis did not reveal any significant correlations between the DNA methylation levels of the 4 CpG sites and the severity of SCZ. GLM revealed significant differences between the 3 groups for CpG site 1 and the average of the 4 CpG sites (P=0.0001 and P=0.0126, respectively). Furthermore, the TD, NTD and TD + NTD groups demonstrated lower methylation levels in CpG site 1 (P=0.0003, P<0.0001 and P<0.0001, respectively) and the average of 4 CpG sites (P=0.0176, P=0.0063 and P=0.003, respectively) compared with the HC group. The results revealed that both NTD and TD patients had significantly decreased DNA methylation levels compared with healthy controls, which indicated a significant association between the DNA methylation levels of the IRS1 gene with SCZ and TD.
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http://dx.doi.org/10.3892/mmr.2020.10984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057828PMC
April 2020

Hippocampus and cognitive domain deficits in treatment-resistant schizophrenia: A comparison with matched treatment-responsive patients and healthy controls.

Psychiatry Res Neuroimaging 2020 Feb 4;297:111043. Epub 2020 Feb 4.

Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, P. R. China. Electronic address:

Some patients with schizophrenia do not respond to pharmacotherapy. More severe cognitive dysfunctions have been associated with treatment-resistant schizophrenia (TRS). This study examines cognitive functions and hippocampal volumes in 43 patients with TRS and compared them to 43 treatment-responsive patients (NTRS), matched on age, sex and education, as well as 53 healthy controls (HC). The results showed that there were significant deficits in all domains of cognition and hippocampal volumes in TRS as compared to HC group. However, TRS specific deficits, as indicated by comparisons with matched NTRS, were limited to poorer performance in working memory (p = 0.003) and smaller total hippocampal volume (p = 0.01). Logistic regression analysis showed that working memory deficits [OR 0.94 (95% CI 0.89-0.98), p = 0.005] and smaller hippocampal volume [OR 0.89 (95% CI 0.81-0.97), p = 0.01], but not their interactions (p = 0.68), contributed to higher risk of treatment resistance. The findings suggest that treatment-resistance to currently available antipsychotic medications may not be due to global cognitive deficits in these patients, but be associated with specific deficits in working memory and hippocampus deficits in the subgroup of schizophrenia.
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http://dx.doi.org/10.1016/j.pscychresns.2020.111043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490244PMC
February 2020
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