Publications by authors named "Xinqi Zhou"

35 Publications

Integrated Analysis of Long Non-Coding RNA and mRNA Expression Profiles in Testes of Calves and Sexually Mature Wandong Bulls ().

Animals (Basel) 2021 Jul 5;11(7). Epub 2021 Jul 5.

College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.

The mRNAs and long non-coding RNAs axes are playing a vital role in the regulating of post-transcriptional gene expression. Thereby, elucidating the expression pattern of mRNAs and long non-coding RNAs underlying testis development is crucial. In this study, mRNA and long non-coding RNAs expression profiles were investigated in 3-month-old calves and 3-year-old mature bulls' testes by total RNA sequencing. Additionally, during the gene level analysis, 21,250 mRNAs and 20,533 long non-coding RNAs were identified. As a result, 7908 long non-coding RNAs (-adjust 0.05) and 5122 mRNAs (-adjust 0.05) were significantly differentially expressed between the distinct age groups. In addition, gene ontology and biological pathway analyses revealed that the predicted target genes are enriched in the lysine degradation, cell cycle, propanoate metabolism, adherens junction and cell adhesion molecules pathways. Correspondingly, the RT-qPCR validation results showed a strong consistency with the sequencing data. The source genes for the mRNAs ( and ) and the long non-coding RNAs ( and ) were found to be actively associated with bull sexual maturity and spermatogenesis. This study provided a comprehensive catalog of long non-coding RNAs in the bovine testes and also offered useful resources for understanding the differences in sexual development caused by the changes in the mRNA and long non-coding RNA interaction expressions between the immature and mature stages.
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http://dx.doi.org/10.3390/ani11072006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300165PMC
July 2021

Origins of Ca Imaging with Fluorescent Indicators.

Biochemistry 2021 Jul 12. Epub 2021 Jul 12.

In 1980, Roger Tsien published a paper, in this journal [Tsien, R. Y. (1980) , (11), 2396], titled "New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures". These new buffers included 1,2-bis(-aminophenoxy)ethane-,,','-tetraacetic acid, or BAPTA, which is still widely used today. And so, the world was set alight with new ways in which to visualize Ca. The ability to watch fluctuations in intracellular Ca revolutionized the life sciences, although the fluorescent indicators used today, particularly in neurobiology, no longer rely exclusively on BAPTA but on genetically encoded fluorescent Ca indicators. In this Perspective, we reflect on the origins of Ca imaging with a special focus on the contributions made by Roger Tsien, from the early concept of selective Ca binding described in to optical Ca indicators based on chemically synthesized fluorophores to genetically encoded fluorescent Ca indicators.
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http://dx.doi.org/10.1021/acs.biochem.1c00350DOI Listing
July 2021

Segregating domain-general from emotional context-specific inhibitory control systems - ventral striatum and orbitofrontal cortex serve as emotion-cognition integration hubs.

Neuroimage 2021 09 15;238:118269. Epub 2021 Jun 15.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu, China. Electronic address:

Inhibitory control hierarchically regulates cognitive and emotional systems in the service of adaptive goal-directed behavior across changing task demands and environments. While previous studies convergently determined the contribution of prefrontal-striatal systems to general inhibitory control, findings on the specific circuits that mediate emotional context-specific impact on inhibitory control remained inconclusive. Against this background we combined an evaluated emotional Go/No Go task with fMRI in a large cohort of subjects (N=250) to segregate brain systems and circuits that mediate domain-general from emotion-specific inhibitory control. Particularly during a positive emotional context, behavioral results showed a lower accuracy for No Go trials and a faster response time for Go trials. While the dorsal striatum and lateral frontal regions were involved in inhibitory control irrespective of emotional context, activity in the ventral striatum (VS) and medial orbitofrontal cortex (mOFC) varied as a function of emotional context. On the voxel-wise whole-brain network level, limbic and striatal systems generally exhibited highest changes in global brain connectivity during inhibitory control, while global brain connectivity of the left mOFC was less decreased during emotional contexts. Functional connectivity analyses moreover revealed that negative coupling between the VS with inferior frontal gyrus (IFG)/insula and mOFC varied as a function of emotional context. Together these findings indicate separable domain- general as well as emotional context-specific inhibitory brain systems which specifically encompass the VS and its connections with frontal regions.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118269DOI Listing
September 2021

Common abnormality of gray matter integrity in substance use disorder and obsessive-compulsive disorder: A comparative voxel-based meta-analysis.

Hum Brain Mapp 2021 Aug 9;42(12):3871-3886. Epub 2021 Jun 9.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

The objective of the current study is to determine robust transdiagnostic brain structural markers for compulsivity by capitalizing on the increasing number of case-control studies examining gray matter volume (GMV) alterations in substance use disorders (SUD) and obsessive-compulsive disorder (OCD). Voxel-based meta-analysis within the individual disorders and conjunction analysis were employed to reveal common GMV alterations between SUDs and OCD. Meta-analytic coordinates and signed brain volumetric maps determining directed (reduced/increased) GMV alterations between the disorder groups and controls served as the primary outcome. The separate meta-analysis demonstrated that SUD and OCD patients exhibited widespread GMV reductions in frontocortical regions including prefrontal, cingulate, and insular. Conjunction analysis revealed that the left inferior frontal gyrus (IFG) consistently exhibited decreased GMV across all disorders. Functional characterization suggests that the IFG represents a core hub in the cognitive control network and exhibits bidirectional (Granger) causal interactions with the striatum. Only OCD showed increased GMV in the dorsal striatum with higher changes being associated with more severe OCD symptomatology. Together the findings demonstrate robustly decreased GMV across the disorders in the left IFG, suggesting a transdiagnostic brain structural marker. The functional characterization as a key hub in the cognitive control network and casual interactions with the striatum suggest that deficits in inhibitory control mechanisms may promote compulsivity and loss of control that characterize both disorders.
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http://dx.doi.org/10.1002/hbm.25471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288096PMC
August 2021

The effects of posture on mind wandering.

Psychol Res 2021 May 21. Epub 2021 May 21.

Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, China.

Using a reading comprehension task, we explored whether body postures would influence mind wandering, a universal internally self-generated activity. Specifically, participants were instructed to perform a reading comprehension task under three postural conditions (lying supine, sitting, and standing upright). Probe-caught technique with prompts presented at irregular intervals was adapted to measure the frequency of mind wandering. Self-caught method was used to measure the meta-awareness of mind wandering by self-reports. Results indicated that the radio of mind wandering was significantly greater in lying than standing and sitting, but the meta-awareness of it was not different among three postures. Moreover, the reading performance, an indirect indicator of executive control, decreased in lying compared to standing and sitting. We suggested that the increase of mind wandering in lying posture may due to the dysfunction of executive control, which also results in the redistribution of cognitive resources. Suggestions for future research are proposed.
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http://dx.doi.org/10.1007/s00426-021-01531-4DOI Listing
May 2021

Oxytocinergic Modulation of Threat-Specific Amygdala Sensitization in Humans Is Critically Mediated by Serotonergic Mechanisms.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Apr 21. Epub 2021 Apr 21.

Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China. Electronic address:

Background: Overarching conceptualizations propose that the complex social-emotional effects of oxytocin (OXT) in humans are partly mediated by interactions with other neurotransmitter systems. Recent animal models suggest that the anxiolytic effects of OXT are critically mediated by the serotonin (5-HT) system, yet direct evidence in humans is lacking.

Methods: To determine the role of 5-HT in OXT-induced attenuation of amygdala threat reactivity and sensitization/desensitization, we conducted a parallel-group, randomized, placebo-controlled, double-blind experiment during which 121 healthy subjects underwent a transient decrease in 5-HT signaling via acute tryptophan depletion or the corresponding placebo-control protocol before the administration of intranasal OXT or placebo intranasal spray, respectively. Mean and repetition-dependent changes in threat-specific amygdala reactivity toward threatening stimuli (angry faces) as assessed by functional magnetic resonance imaging served as the primary outcome.

Results: No main or interaction effects of treatment on amygdala threat reactivity were observed, yet OXT switched bilateral amygdala threat sensitization to desensitization, and this effect was significantly attenuated during decreased central 5-HT signaling via pretreatment with acute tryptophan depletion.

Conclusions: The present findings provide the first evidence for a role of OXT in threat-specific amygdala desensitization in humans and suggest that these effects are critically mediated by the 5-HT system. OXT may have a therapeutic potential to facilitate amygdala desensitization, and adjunct upregulation of 5-HT neurotransmission may facilitate OXT's anxiolytic potential.
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http://dx.doi.org/10.1016/j.bpsc.2021.04.009DOI Listing
April 2021

Disorder- and emotional context-specific neurofunctional alterations during inhibitory control in generalized anxiety and major depressive disorder.

Neuroimage Clin 2021 3;30:102661. Epub 2021 Apr 3.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for NeuroInformation, High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China. Electronic address:

Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) are highly debilitating and often co-morbid disorders. The disorders exhibit partly overlapping dysregulations on the behavioral and neurofunctional level. The determination of disorder-specific behavioral and neurofunctional dysregulations may therefore promote neuro-mechanistic and diagnostic specificity. In order to determine disorder-specific alterations in the domain of emotion-cognition interactions the present study examined emotional context-specific inhibitory control in treatment-naïve MDD (n = 37) and GAD (n = 35) patients and healthy controls (n = 35). On the behavioral level MDD but not GAD exhibited impaired inhibitory control irrespective of emotional context. On the neural level, MDD-specific attenuated recruitment of inferior/medial parietal, posterior frontal, and mid-cingulate regions during inhibitory control were found during the negative context. GAD exhibited a stronger engagement of the left dorsolateral prefrontal cortex relative to MDD. Overall the findings from the present study suggest disorder- and emotional context-specific behavioral and neurofunctional inhibitory control dysregulations in major depression and may point to a depression-specific neuropathological and diagnostic marker.
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http://dx.doi.org/10.1016/j.nicl.2021.102661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060548PMC
July 2021

Common neurofunctional dysregulations characterize obsessive-compulsive, substance use, and gaming disorders-An activation likelihood meta-analysis of functional imaging studies.

Addict Biol 2021 07 11;26(4):e12997. Epub 2021 Jan 11.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

Compulsivity and loss of behavioral control represent core symptoms in obsessive-compulsive disorder (OCD), substance use disorder (SUD), and internet gaming disorder (IGD). Despite elaborated animal models suggesting that compulsivity is mediated by cortico-striatal circuits and a growing number of neuroimaging case-control studies, common neurofunctional alterations in these disorders have not been systematically examined. The present activation likelihood estimation (ALE) meta-analysis capitalized on previous functional magnetic resonance imaging (fMRI) studies to determine shared neurofunctional alterations among the three disorders. Task-based fMRI studies of individuals with SUD, OCD, or IGD were obtained. ALE was performed within each disorder. Next, contrast and conjunction meta-analyses were performed to determine differential and common alterations. Task-paradigm classes were group according to Research Domain Criteria (RDoC) domains to determine contributions of underlying behavioral domains. One hundred forty-four articles were included representing data from n = 6897 individuals (SUD = 2418, controls = 2332; IGD = 361, controls = 360; OCD = 715, controls = 711) from case-control studies. Conjunction meta-analyses revealed shared alterations in the anterior insular cortex between OCD and SUDs. SUD exhibited additionally pronounced dorsal-striatal alterations compared with both, OCD and IGD. IGD shared frontal, particularly cingulate alterations with all SUDs, while IGD demonstrated pronounced temporal alterations compared with both, SUD and OCD. No robust overlap between IGD and OCD was observed. Across the disorders, neurofunctional alterations were mainly contributed by cognitive systems and positive valence RDoC domains. The present findings indicate that neurofunctional dysregulations in prefrontal regions engaged in regulatory-control represent shared neurofunctional alterations across substance and behavioral addictions, while shared neurofunctional dysregulations in the anterior insula may mediate compulsivity in substance addiction and OCD.
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http://dx.doi.org/10.1111/adb.12997DOI Listing
July 2021

Putamen volume predicts real-time fMRI neurofeedback learning success across paradigms and neurofeedback target regions.

Hum Brain Mapp 2021 04 5;42(6):1879-1887. Epub 2021 Jan 5.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, University of Electronic Science and Technology of China, Chengdu, China.

Real-time fMRI guided neurofeedback training has gained increasing interest as a noninvasive brain regulation technique with the potential to modulate functional brain alterations in therapeutic contexts. Individual variations in learning success and treatment response have been observed, yet the neural substrates underlying the learning of self-regulation remain unclear. Against this background, we explored potential brain structural predictors for learning success with pooled data from three real-time fMRI data sets. Our analysis revealed that gray matter volume of the right putamen could predict neurofeedback learning success across the three data sets (n = 66 in total). Importantly, the original studies employed different neurofeedback paradigms during which different brain regions were trained pointing to a general association with learning success independent of specific aspects of the experimental design. Given the role of the putamen in associative learning this finding may reflect an important role of instrumental learning processes and brain structural variations in associated brain regions for successful acquisition of fMRI neurofeedback-guided self-regulation.
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http://dx.doi.org/10.1002/hbm.25336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978128PMC
April 2021

Oxytocin-induced facilitation of learning in a probabilistic task is associated with reduced feedback- and error-related negativity potentials.

J Psychopharmacol 2021 01 4;35(1):40-49. Epub 2020 Dec 4.

MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China.

Background: Feedback evaluation of actions and error response detection are critical for optimizing behavioral adaptation. Oxytocin can facilitate learning following social feedback but whether its effects vary as a function of feedback valence remains unclear.

Aims: The present study aimed to investigate whether oxytocin would influence responses to positive and negative feedback differentially or equivalently.

Methods: The present study employed a randomized, double-blind, placebo controlled within-subject design to investigate whether intranasal oxytocin (24 IU) influenced behavioral and evoked electrophysiological potential responses to positive or negative feedback in a probabilistic learning task.

Results: Results showed that oxytocin facilitated learning and this effect was maintained in the absence of feedback. Using novel stimulus pairings, we found that oxytocin abolished bias towards learning more from negative feedback under placebo by increasing accuracy for positively reinforced stimuli. Oxytocin also decreased the feedback-related negativity difference (negative minus positive feedback) during learning, further suggesting that it rendered the evaluation of positive and negative feedback more equivalent. Additionally, post-learning oxytocin attenuated error-related negativity amplitudes but increased the late error positivity, suggesting that it may lower conflict detection between actual errors and expected correct responses at an early stage of processing but at a later stage increase error awareness and motivation for avoiding them.

Conclusions: Oxytocin facilitates learning and subsequent performance by rendering the impact of positive relative to negative feedback more equivalent and also by reducing conflict detection and increasing error awareness, which may be beneficial for behavioral adaption.
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http://dx.doi.org/10.1177/0269881120972347DOI Listing
January 2021

Higher levels of (Internet) Gaming Disorder symptoms according to the WHO and APA frameworks associate with lower striatal volume.

J Behav Addict 2020 Oct 2;9(3):598-605. Epub 2020 Oct 2.

1The Clinical Hospital of the Chengdu Brain Science Institute, Key Laboratory for NeuroInformation, University of Electronic Science and Technology of China, Chengdu, China.

Background And Aims: Growing concerns about the addictive nature of Internet and computer games led to the preliminary recognition of Internet Gaming Disorder (IGD) as an emerging disorder by the American Psychiatric Association (APA) and the official recognition of Gaming Disorder (GD) as a new diagnosis by the World Health Organization (WHO). While the definition of clear diagnostic criteria for (I)GD represents an important step for diagnosis and treatment of the disorder, potential neurobiological correlates of the criteria remain to be explored.

Methods: The present study employed a dimensional Magnetic Resonance Imaging (MRI) approach to determine associations between (I)GD symptom-load according to the APA and WHO diagnostic frameworks and brain structure in a comparably large sample of n = 82 healthy subjects.

Results: Higher symptom-load on both, the APA and WHO diagnostic frameworks convergently associated with lower volumes of the striatum.

Discussion: The results from this exploratory study provide the first initial evidence for a neurobiological foundation of the proposed diagnostic criteria for (I)GD according to both diagnostic classification systems and suggest that the transition from non-disordered to disordered gaming may be accompanied by progressive neuroplastic changes in the striatum, thus resembling progressive changes in other addictive disorders.

Conclusions: The proposed (I)GD criteria in both diagnostic systems were associated with neurostructural alterations in the striatum, suggesting an association with progressive changes in the motivational systems of the brain.
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http://dx.doi.org/10.1556/2006.2020.00066DOI Listing
October 2020

Intrinsic connectivity of the prefrontal cortex and striato-limbic system respectively differentiate major depressive from generalized anxiety disorder.

Neuropsychopharmacology 2021 03 22;46(4):791-798. Epub 2020 Sep 22.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for NeuroInformation, University of Electronic Science and Technology of China, Chengdu, 610054, Sichuan, China.

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly prevalent and debilitating disorders. The high overlap on the symptomatic and neurobiological level led to ongoing debates about their diagnostic and neurobiological uniqueness. The present study aims to identify common and disorder-specific neuropathological mechanisms and treatment targets in MDD and GAD. To this end we combined categorical and dimensional disorder models with a fully data-driven intrinsic network-level analysis (intrinsic connectivity contrast, ICC) to resting-state fMRI data acquired in 108 individuals (n = 35 and n = 38 unmedicated patients with first-episode GAD, MDD, respectively, and n = 35 healthy controls). Convergent evidence from categorical and dimensional analyses revealed MDD-specific decreased whole-brain connectivity profiles of the medial prefrontal and dorsolateral prefrontal cortex while GAD was specifically characterized by decreased whole-brain connectivity profiles of the putamen and decreased communication of this region with the amygdala. Together, findings from the present data-driven analysis suggest that intrinsic communication of frontal regions engaged in executive functions and emotion regulation represent depression-specific neurofunctional markers and treatment targets whereas dysregulated intrinsic communication of the striato-amygdala system engaged in reinforcement-based and emotional learning processes represent GAD-specific markers.
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http://dx.doi.org/10.1038/s41386-020-00868-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027677PMC
March 2021

Prevalence and Psychosocial Correlates of Mental Health Outcomes Among Chinese College Students During the Coronavirus Disease (COVID-19) Pandemic.

Front Psychiatry 2020 7;11:803. Epub 2020 Aug 7.

Early Psychosis: Intervention and Clinical-detection (EPIC) lab, Department of Psychosis Studies, King's College London, London, United Kingdom.

Objectives: To investigate the prevalence and risk factors for poor mental health of Chinese university students during the Corona Virus Disease 2019 (COVID-19) pandemic.

Method: Chinese nation-wide on-line cross-sectional survey on university students, collected between February 12 and 17, 2020. Primary outcome was prevalence of clinically-relevant posttraumatic stress disorder symptoms. Secondary outcomes on poor mental health included prevalence of clinically-relevant anxiety and depressive symptoms, while posttraumatic growth was considered as indicator of effective coping reaction.

Results: Of 2,500 invited Chinese university students, 2,038 completed the survey. Prevalence of clinically-relevant PTSD, anxiety, and depressive symptoms, and post traumatic growth (PTG) was 30.8, 15.5, 23.3, and 66.9% respectively. Older age, knowing people who had been isolated, more ACEs, higher level of anxious attachment, and lower level of resilience all predicted primary outcome (all < 0.01).

Conclusions: A significant proportion of young adults exhibit clinically relevant posttraumatic stress disorder (PTSD), anxious or depressive symptoms, but a larger portion of individuals showed to effectively cope with COVID-19 pandemic. Interventions promoting resilience should be provided, even remotely, to those subjects with specific risk factors to develop poor mental health during COVID-19 or other pandemics with social isolation.
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http://dx.doi.org/10.3389/fpsyt.2020.00803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427603PMC
August 2020

Oxytocin Differentially Modulates Amygdala Responses during Top-Down and Bottom-Up Aversive Anticipation.

Adv Sci (Weinh) 2020 Aug 1;7(16):2001077. Epub 2020 Jul 1.

The Clinical Hospital of Chengdu Brain Science Institute MOE Key Laboratory for Neuroinformation University of Electronic Science and Technology of China Xiyuan Avenue 2006 Chengdu 611731 China.

The ability to successfully regulate negative emotions such as fear and anxiety is vital for mental health. Intranasal administration of the neuropeptide oxytocin (OXT) has been shown to reduce amygdala activity but to increase amygdala-prefrontal cortex connectivity during exposure to threatening stimuli suggesting that it may act as an important modulator of emotion regulation. The present randomized, between-subject, placebo-controlled pharmacological study combines the intranasal administration of OXT with functional magnetic resonance imaging (fMRI) during an explicit emotion regulation paradigm in 65 healthy male participants to investigate the modulatory effects of OXT on both bottom-up and top-down emotion regulation. OXT attenuates the activation in the posterior insular cortex and amygdala during anticipation of top-down regulation of predictable threat stimuli in participants with high trait anxiety. In contrast, OXT enhances amygdala activity during the bottom-up anticipation of unpredictable threat stimuli in participants with low trait anxiety. OXT may facilitate top-down goal-directed attention by attenuating amygdala activity in high anxiety individuals, while promoting bottom-up attention/vigilance to unexpected threats by enhancing amygdala activity in low anxiety individuals. OXT may thus have the potential to promote an adaptive balance between bottom-up and top-down attention systems depending on an individual's trait anxiety level.
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http://dx.doi.org/10.1002/advs.202001077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435249PMC
August 2020

Regulatory functions of gga-miR-218 in spermatogonial stem cells meiosis by targeting Stra8.

Mech Dev 2020 12 13;164:103636. Epub 2020 Aug 13.

College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, Jiangsu province, PR China; Key Laboratory for Animal Genetics, Breeding, Reproduction, and Molecular Design of Jiangsu Province, Yangzhou 225009, Jiangsu province, PR China. Electronic address:

MicroRNAs play a crucial role in sperm formation, but its specific function remains unknown. Here, we found that gga-miR-218 regulates chicken sperm formation through in/ex vivo experiments. We constructed over-expression/interference carrier to overexpress and inhibit gga-miR-218 in chicken spermatogonial stem cells, separately, the detection of haploid and QRT-PCR of meiosis related genes revealed that gga-miR-218 inhibits meiosis. After injection of miR-218 in vivo, semen concentration and HE (Hematoxylin and Eosin staining) revealed that gga-miR-218 inhibits meiosis. Meanwhile, we discovered that gga-miR-218 could target Stra8 by prediction software which can inhibit the wild-type fluorescence activity by co-transfection of gga-miR-218 with the Stra8 3' untranslated regions fluorescent reporter vector (wild-type/mutant), QRT-PCR and Western blot showed that gga-miR-218 inhibits the expression level of Stra8 by targeting its 3' untranslated regions directly. Finally, we suggest that gga-miR-218 could target to srta8 directly and inhibit spermatogenesis.
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http://dx.doi.org/10.1016/j.mod.2020.103636DOI Listing
December 2020

An Evolutionary Strategy for Identification of Higher Order, Green Fluorescent Host-Guest Pairs Compatible with Living Systems.

Chemistry 2020 Dec 9;26(70):16721-16726. Epub 2020 Nov 9.

Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA.

Engineered miniprotein host-small-molecule guest pairs could be utilized to design new processes within cells as well as investigate fundamental aspects of cell signaling mechanisms. However, the development of host-guest pairs capable of functioning in living systems has proven challenging. Moreover, few examples of host-guest pairs with stoichiometries other than 2:1 exist, significantly hindering the ability to study the influence of oligomerization state on signaling fidelity. Herein, we present an approach to identify host-guest systems for relatively small green fluorescent guests by incorporation into cyclic peptides. The optimal host-guest pair produced a 10-fold increase in green fluorescence signal upon binding. Biophysical characterization clearly demonstrated higher order supramolecular assembly, which could be visualized on the surface of living yeast cells using a turn-on fluorescence readout. This work further defines evolutionary design principles to afford host-guest pairs with stoichiometries other than 2:1 and enables the identification of spectrally orthogonal host-guest pairs.
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http://dx.doi.org/10.1002/chem.202002423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744332PMC
December 2020

Synthesis and application of a ratiometric probe for hydrogen peroxide.

Methods Enzymol 2020 29;639:23-36. Epub 2020 Apr 29.

Department of Chemistry, University of Virginia, Charlottesville, VA, United States. Electronic address:

Molecular imaging of biological analytes provides detailed insights into signaling processes. Ratiometric probes are particularly attractive due to the ability to quantify analyte production. However, design strategies for ratiometric probes can be hindered by spectral overlap of the product and reactant species. In this chapter, we provide protocols for the synthesis and application of RF, a ratiometric probe for HO displaying dramatic changes in both excitation and emission wavelengths, designed using an approach we term chemoselective alteration of fluorophore scaffolds. The probe contains a chemoselective functional group within a fluorescent xanthene scaffold, resulting in the in situ synthesis of a new fluorophore upon reaction with HO. Under physiological conditions, RF exhibits far-red to near-infrared excitation and emission, and upon reaction with HO, RF is chemically converted into tetramethylrhodamine, producing a significant (~66nm) blue-shift in excitation and emission. RF can be used for ratiometric, molecular imaging of endogenous HO production in living cells.
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http://dx.doi.org/10.1016/bs.mie.2020.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266825PMC
June 2021

Effective Self-Management for Early Career Researchers in the Natural and Life Sciences.

Neuron 2020 04;106(2):212-217

Department of Psychology, Florida International University, 8th Street, DM 256 Miami, FL 33199, USA.

Early career researchers (ECRs) are faced with a range of competing pressures in academia, making self-management key to building a successful career. The Organization for Human Brain Mapping undertook a group effort to gather helpful advice for ECRs in self-management.
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http://dx.doi.org/10.1016/j.neuron.2020.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665085PMC
April 2020

Imaging GPCR internalization using near-infrared Nebraska red-based reagents.

Org Biomol Chem 2020 04;18(13):2459-2467

Department of Chemistry, University of Nebraska - Lincoln, Lincoln, NE 68588, USA. and Department of Chemistry, University of Virginia, Charlottesville, VA 22904, USA and Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, NE 68588, USA and Cancer Genes and Molecular Regulation Program, Fred & Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Internalization of G protein-coupled receptor (GPCRs) represents a nearly universal pathway for receptor downregulation. Imaging this process provides a means for the identification of pharmaceutical agents as well as potential ligands for orphan receptors. However, there is a need for the further development of near-infrared (NIR) probes capable of monitoring internalization in order to enable multiplexing with existing green fluorescent GPCR activity assays. Our laboratory has recently described a series of near-infrared (NIR) fluorophores in which a phosphinate functionality is inserted at the bridging position of the xanthene scaffold. These fluorophores, termed Nebraska Red (NR) dyes, provide attractive reagents for imaging protein localization. Herein, we disclose the development of NR-based HaloTag ligands for imaging membrane proteins on living cells. These new probes are utilized to image membrane pools of the human orexin type 2 receptor, an established target for the treatment of insomnia. We demonstrate the ability of fetal bovine serum (FBS) to noncovalently associate with a spirolactonized NR probe, enabling no-wash imaging with a 45-fold enhancement of fluorescence. Furthermore, we characterize the utility of NR-based HaloTag ligands for real-time monitoring of receptor internalization upon agonist stimulation. These new reagents enable potential multiplexing with existing GPCR activity assays in order to identify new modulators of GPCR activity as well as ligands for orphan receptors.
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http://dx.doi.org/10.1039/d0ob00043dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261517PMC
April 2020

Common and Disorder-Specific Neurofunctional Markers of Dysregulated Empathic Reactivity in Major Depression and Generalized Anxiety Disorder.

Psychother Psychosom 2020 26;89(2):114-116. Epub 2019 Nov 26.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China,

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http://dx.doi.org/10.1159/000504180DOI Listing
February 2021

Impaired cognitive performance under psychosocial stress in cannabis-dependent men is associated with attenuated precuneus activity

J Psychiatry Neurosci 2020 03;45(2):88-97

From the Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China (Zhao, Zhou, Zhou, Fu, Kendrick, Becker); the Department of Psychiatry and Division of Medical Psychology, University of Bonn, Bonn, Germany (Zimmermann, Dernbach, Scheele, Hurlemann); the Center for Economics and Neuroscience, Department of Epileptology, University of Bonn, Bonn, Germany (Weber); the Department of NeuroCognition, Life and Brain Center, Bonn, Germany (Weber); and the Institute of Medical Psychology, Center for Psychosocial Medicine, University Hospital, Heidelberg University, Heidelberg, Germany (Eckstein).

Background: Deficient regulation of stress plays an important role in the escalation of substance use, addiction and relapse. Accumulating evidence suggests dysregulations in cognitive and reward-related processes and the underlying neural circuitry in cannabis dependence. However, despite the important regulatory role of the endocannabinoid system in the stress response, associations between chronic cannabis use and altered stress processing at the neural level have not been systematically examined.

Methods: Against this background, the present functional MRI study examined psychosocial stress processing in cannabis-dependent men (n = 28) and matched controls (n = 23) using an established stress-induction paradigm (Montreal Imaging Stress Task) that combines computerized (adaptive) mental arithmetic challenges with social evaluative threat.

Results: During psychosocial stress exposure, but not the no-stress condition, cannabis users demonstrated impaired performance relative to controls. In contrast, levels of experienced stress and cardiovascular stress responsivity did not differ from controls. Functional MRI data revealed that stress-induced performance deteriorations in cannabis users was accompanied by decreased precuneus activity and increased connectivity of this region with the superior frontal gyrus.

Limitations: Only male cannabis-dependent users were examined; the generalizability in female users remains to be determined.

Conclusion: Together, the present findings provide first evidence for exaggerated stress-induced cognitive performance deteriorations in cannabis users. The neural data suggest that deficient stress-related recruitment of the precuneus may be associated with the deterioration of performance at the behavioural level.
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http://dx.doi.org/10.1503/jpn.190039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828906PMC
March 2020

Hamartoma of mature cardiomyocytes in right atrium: A case report and literature review.

Medicine (Baltimore) 2019 Aug;98(31):e16640

Department of Cardiovascular Surgery.

Rationale: Tumors in the heart are rare. Myxomas, rhabdomyomas, and fibromas are the most common benign cardiac tumors. Hamartoma of mature cardiomyocytes (HMCM) is another benign cardiac tumor, are very rare and have only been reported in a few literatures.

Patient Concerns: We report a case of 41-year-old male who suffered short of breath for 3 years, and lower limbs edema for 2 years.

Diagnoses: Transthoracic echocardiogram (TTE) and cardiac magnetic resonance (CMR) showed a large amount of pericardial effusion and confirmed a mass of 18 × 14 mm on the superior vena cava near the outer edge of right atrium. The patient was first diagnosed as pleural mesothelioma. Surgery was performed to relieve the symptoms and confirm diagnoses. However, during surgery, we found the right atrium is apparently thicken with rough and uneven surface. Histology of right atrium mass indicated it as hamartoma of mature cardiomyocytes.

Intervention: We resected the thicken atrial wall completely, reconstructed right atrium with bovine pericardial patch, and resected the pericardium.

Outcomes: Patient was discharged 9 days after surgery, and remained asymptomatic during 9 months follow up.

Lessons: Hamartoma of mature cardomyocytes is a rare benign cardiac tumor. There were 26 cases reported until now. The conclusive diagnosis depends on pathological sections. For patients with symptoms, surgery is an effective treatment for HMCM.
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http://dx.doi.org/10.1097/MD.0000000000016640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709070PMC
August 2019

Cue Reactivity in the Ventral Striatum Characterizes Heavy Cannabis Use, Whereas Reactivity in the Dorsal Striatum Mediates Dependent Use.

Biol Psychiatry Cogn Neurosci Neuroimaging 2019 08 22;4(8):751-762. Epub 2019 Apr 22.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China. Electronic address:

Background: Animal models of addiction suggest that the transition from incentive-driven drug use to habitual and ultimately compulsive drug use is mediated by a shift from ventral to dorsal striatal cue control over drug seeking. Previous studies in human cannabis users reported elevated trait impulsivity and neural cue reactivity in striatal circuits; however, these studies were not able to separate addiction-related from exposure-related adaptations.

Methods: To differentiate the adaptive changes, the current functional magnetic resonance imaging study examined behavioral and neural cue reactivity in dependent (n = 18) and nondependent (n = 20) heavy cannabis users and a nonusing reference group (n = 44).

Results: Irrespective of dependence status, cannabis users demonstrated elevated trait impulsivity as well as increased ventral striatal reactivity and striatal frontal coupling in response to drug cues. Dependent users selectively exhibited dorsal striatal reactivity and decreased striatal limbic coupling during cue exposure. An exploratory analysis revealed that higher ventral caudate neural cue reactivity was associated with stronger cue-induced arousal and craving in dependent users, whereas this pattern was reversed in nondependent users.

Conclusions: Taken together, the current findings suggest that exaggerated responses of the ventral striatal reward system may promote excessive drug use in humans, whereas adaptations in dorsal striatal systems engaged in habit formation may promote the transition to addictive use.
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http://dx.doi.org/10.1016/j.bpsc.2019.04.006DOI Listing
August 2019

Oxytocin Facilitates Self-Serving Rather Than Altruistic Tendencies in Competitive Social Interactions Via Orbitofrontal Cortex.

Int J Neuropsychopharmacol 2019 08;22(8):501-512

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for NeuroInformation, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

Background: While the neuropeptide oxytocin can facilitate empathy and altruistic behavior, it may also promote self-serving tendencies in some contexts, and it remains unclear if it would increase altruistic or self-interest behaviors when they compete within a social situation.

Methods: The current between-subject, double-blind, placebo-controlled fMRI study investigated the effect of intranasal oxytocin on empathy for social exclusion using a modified online ball-tossing game that incorporated monetary rewards and the potential to display both altruistic and self-interest behaviors.

Results: Results showed that when subjects in both oxytocin and placebo groups were observing a player being excluded (victim) by other players in the game, there was activation in the mentalizing network. When subjects then played both with the victim and the players who had excluded them, they threw more balls to the victim player, indicative of an altruistic response. However, subjects in the oxytocin group threw more balls to the excluder players indicative of greater self-interest, since the latter would be perceived as more likely to reciprocate to maximize financial gain. This behavioral effect of oxytocin was associated with greater medial orbitofrontal cortex activation when playing with the excluders and negatively correlated with trait-altruism scores.

Conclusions: Overall, our findings suggest that in the context of competing motivations for exhibiting altruistic or self-interest behavior, oxytocin enhanced self-interest and this was associated with greater activation in frontal reward areas.
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http://dx.doi.org/10.1093/ijnp/pyz028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672625PMC
August 2019

Phosphinate-containing rhodol and fluorescein scaffolds for the development of bioprobes.

Chem Commun (Camb) 2019 May 3;55(42):5962-5965. Epub 2019 May 3.

Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA. and Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, NE 68588, USA and Cancer Genes and Molecular Regulation Program, Fred & Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.

A series of phosphinate-containing rhodol and fluorescein dyes are disclosed. These new fluorophores increase the color palette of phosphinate-based xanthenes in the far-red spectral region. The new chemical functionality of these scaffolds is leveraged to produce a sensitive, no-wash imaging probe for cellular esterase activity. The reported phosphinate-containing dyes provide platforms for the further development of imaging probes and self-reporting delivery vehicles.
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http://dx.doi.org/10.1039/c9cc02492aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540752PMC
May 2019

A Phosphinate-Containing Fluorophore Capable of Selectively Inducing Apoptosis in Cancer Cells.

Chembiochem 2019 07 3;20(13):1712-1716. Epub 2019 May 3.

Department of Chemistry, University of Nebraska, Lincoln, NE, 68588, USA.

Chemotherapeutic agents generally suffer from off-target cytotoxicity in noncancerous cell types, leading to undesired side effects. As a result, significant effort has been put into identifying compounds that are selective for cancerous over noncancerous cell types. Our laboratory has recently developed a series of near-infrared (NIR) fluorophores containing a phosphinate functionality at the bridging position of a xanthene scaffold, termed Nebraska Red (NR) fluorophores. Herein, we report the selective cytotoxicity of one NR derivative, NR , against HeLa (cervical cancer) cells versus NIH-3T3 (noncancerous fibroblast) cells. Mechanistic studies based on the NIR fluorescence signal of NR showed distinct subcellular localization in HeLa (mitochondrial) versus NIH-3T3 (lysosomal) that resulted from the elevated mitochondrial potential in HeLa cells. This study provides a new, NIR scaffold for the further development of reagents for targeted cancer therapy.
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http://dx.doi.org/10.1002/cbic.201800811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663559PMC
July 2019

Oxytocin Modulates the Intrinsic Dynamics Between Attention-Related Large-Scale Networks.

Cereb Cortex 2021 02;31(3):1848-1860

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, 611731 Chengdu, China.

Attention and salience processing have been linked to the intrinsic between- and within-network dynamics of large-scale networks engaged in internal (default network [DN]) and external attention allocation (dorsal attention network [DAN] and salience network [SN]). The central oxytocin (OXT) system appears ideally organized to modulate widely distributed neural systems and to regulate the switch between internal attention and salient stimuli in the environment. The current randomized placebo (PLC)-controlled between-subject pharmacological resting-state fMRI study in N = 187 (OXT, n = 94; PLC, n = 93; single-dose intranasal administration) healthy male and female participants employed an independent component analysis approach to determine the modulatory effects of OXT on the within- and between-network dynamics of the DAN-SN-DN triple network system. OXT increased the functional integration between subsystems within SN and DN and increased functional segregation of the DN with both attentional control networks (SN and DAN). Whereas no sex differences were observed, OXT effects on the DN-SN interaction were modulated by autistic traits. Together, the findings suggest that OXT may facilitate efficient attention allocation by modulating the intrinsic functional dynamics between DN components and large-scale networks involved in external attentional demands (SN and DAN).
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http://dx.doi.org/10.1093/cercor/bhy295DOI Listing
February 2021

Wandering Minds with Wandering Brain Networks.

Authors:
Xinqi Zhou Xu Lei

Neurosci Bull 2018 Dec 22;34(6):1017-1028. Epub 2018 Aug 22.

Sleep and NeuroImaging Center, Faculty of Psychology, Southwest University, Chongqing, 400715, China.

The default mode network (DMN) is associated with the occurrence of mind-wandering or task-unrelated thought. In contrast, the frontal-parietal network (FPN) and visual network (VS) are involved in tasks with external stimuli. However, it is not clear how these functional network interactions support these two different processes - mind-wandering and on-task - especially with regard to individual variation in the mind-wandering experience. In this study, we investigated the functional connectivity and modular structure among the DMN, FPN, and VS. Our results showed that, compared to the on-task period, mind-wandering was associated with increased DMN activity and increased DMN-VS connectivity. Moreover, mind-wandering was accompanied by a large number of transitional nodes, which expressed a diversity of brain regions. Intriguingly, the functional connectivity of the FPN and VS was strongly correlated with individual behavioral performance. Our findings highlight the individual variation of mind-wandering, which implies the importance of other complementary large-scale brain networks.
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http://dx.doi.org/10.1007/s12264-018-0278-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246840PMC
December 2018

Chemoselective Alteration of Fluorophore Scaffolds as a Strategy for the Development of Ratiometric Chemodosimeters.

Angew Chem Int Ed Engl 2017 04 20;56(15):4197-4200. Epub 2017 Mar 20.

Department of Chemistry, University of Nebraska - Lincoln, Lincoln, NE, 68588, USA.

Ratiometric sensors generally couple binding events or chemical reactions at a distal site to changes in the fluorescence of a core fluorophore scaffold. However, such approaches are often hindered by spectral overlap of the product and reactant species. We provide a strategy to design ratiometric sensors that display dramatic spectral shifts by leveraging the chemoselective reactivity of novel functional groups inserted within fluorophore scaffolds. As a proof-of-principle, fluorophores containing a borinate (RF ) or silanediol (SiOH2R) functionality at the bridging position of the xanthene ring system are developed as endogenous H O sensors. Both these fluorophores display far-red to near-infrared excitation and emission prior to reaction. Upon oxidation by H O both sensors are chemically converted to tetramethylrhodamine, producing significant (≥66 nm) blue-shifts in excitation and emission maxima. This work provides a new concept for the development of ratiometric probes.
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http://dx.doi.org/10.1002/anie.201612628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453638PMC
April 2017

Sleep Deprivation Makes the Young Brain Resemble the Elderly Brain: A Large-Scale Brain Networks Study.

Brain Connect 2017 02;7(1):58-68

1 Sleep and NeuroImaging Center, Faculty of Psychology, Southwest University , Chongqing, China .

Decreased cognition performance and impaired brain function are similar results of sleep deprivation (SD) and aging, according to mounted supporting evidence. Some investigators even proposed SD as a model of aging. However, few direct comparisons were ever explored between the effects of SD and aging by network module analysis with the resting-state functional magnetic resonance imaging. In this study, both within-module and between-module (BT) connectivities were calculated in the whole brain to describe a complete picture of brain networks' functional connectivity among three groups (young normal sleep, young SD, and old group). The results showed that the BT connectivities in subcortical and cerebellar networks were significantly declined in both the young SD group and old group. There were six other networks, that is, ventral attention, dorsal attention, default mode, auditory, cingulo-opercular, and memory retrieval networks, significantly influenced by aging. Therefore, we speculated that the effects of SD on the young group can be regarded as a simplified model of aging. Moreover, this provided a possible explanation, that is, the old were more tolerable for SD than the young. However, SD may not be a considerable model for aging when discussing the brain regions related to those SD-uninfluenced networks.
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http://dx.doi.org/10.1089/brain.2016.0452DOI Listing
February 2017
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