Publications by authors named "Xiaochun Xie"

31 Publications

Mild traumatic brain injury induces microvascular injury and accelerates Alzheimer-like pathogenesis in mice.

Acta Neuropathol Commun 2021 Apr 23;9(1):74. Epub 2021 Apr 23.

Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.

Introduction: Traumatic brain injury (TBI) is considered as the most robust environmental risk factor for Alzheimer's disease (AD). Besides direct neuronal injury and neuroinflammation, vascular impairment is also a hallmark event of the pathological cascade after TBI. However, the vascular connection between TBI and subsequent AD pathogenesis remains underexplored.

Methods: In a closed-head mild TBI (mTBI) model in mice with controlled cortical impact, we examined the time courses of microvascular injury, blood-brain barrier (BBB) dysfunction, gliosis and motor function impairment in wild type C57BL/6 mice. We also evaluated the BBB integrity, amyloid pathology as well as cognitive functions after mTBI in the 5xFAD mouse model of AD.

Results: mTBI induced microvascular injury with BBB breakdown, pericyte loss, basement membrane alteration and cerebral blood flow reduction in mice, in which BBB breakdown preceded gliosis. More importantly, mTBI accelerated BBB leakage, amyloid pathology and cognitive impairment in the 5xFAD mice.

Discussion: Our data demonstrated that microvascular injury plays a key role in the pathogenesis of AD after mTBI. Therefore, restoring vascular functions might be beneficial for patients with mTBI, and potentially reduce the risk of developing AD.
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http://dx.doi.org/10.1186/s40478-021-01178-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063402PMC
April 2021

Functional Mapping of AGO-Associated Zika Virus-Derived Small Interfering RNAs in Neural Stem Cells.

Front Cell Infect Microbiol 2021 25;11:628887. Epub 2021 Feb 25.

Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.

Viral interfering RNA (viRNA) has been identified from several viral genomes directly deep RNA sequencing of the virus-infected cells, including zika virus (ZIKV). Once produced by endoribonuclease Dicer, viRNAs are loaded onto the Argonaute (AGO) family proteins of the RNA-induced silencing complexes (RISCs) to pair with their RNA targets and initiate the cleavage of target genes. However, the identities of functional ZIKV viRNAs and their viral RNA targets remain largely unknown. Our recent study has shown that ZIKV capsid protein interacted with Dicer and antagonized its endoribonuclease activity, which requires its histidine residue at the 41 amino acid. Accordingly, the engineered ZIKV-H41R loss-of-function (LOF) mutant virus no longer suppresses Dicer enzymatic activity nor inhibits miRNA biogenesis in NSCs. By combining AGO-associated RNA sequencing, deep sequencing analysis in ZIKV-infected human neural stem cells (NSCs), and miRanda target scanning, we defined 29 ZIKV derived viRNA profiles in NSCs, and established a complex interaction network between the viRNAs and their viral targets. More importantly, we found that viRNA production from the ZIKV mRNA is dependent on Dicer function and is a limiting factor for ZIKV virulence in NSCs. As a result, much higher levels of viRNAs generated from the ZIKV-H41R virus-infected NSCs. Therefore, our mapping of viRNAs to their RNA targets paves a way to further investigate how viRNAs play the role in anti-viral mechanisms, and perhaps other unknown biological functions.
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http://dx.doi.org/10.3389/fcimb.2021.628887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946837PMC
February 2021

Mother Phubbing and Adolescent Cyberbullying: The Mediating Role of Perceived Mother Acceptance and the Moderating Role of Emotional Stability.

J Interpers Violence 2020 Dec 28:886260520983905. Epub 2020 Dec 28.

Department of Psychology, Renmin University of China, Beijing, China.

Previous studies have found some risk factors of cyberbullying. However, little is known about how mother phubbing may influence adolescent cyberbullying, and the mediating and moderating mechanisms underlying this relationship. "Phubbing," which is a portmanteau of "phone" and "subbing," refers to snubbing other people and focus on smartphones in social interactions. This study examined whether mother phubbing, which refers to being phubbed by one's mother, would be positively related to adolescent cyberbullying, whether perceived mother acceptance would mediate the relationship between mother phubbing and adolescent cyberbullying, and whether emotional stability would moderate the pathways between mother phubbing and adolescent cyberbullying. The sample consisted of 4,213 Chinese senior high school students (mean age 16.41 years, = 0.77, 53% were female). Participants completed measurements regarding mother phubbing, cyberbullying, perceived mother acceptance, and emotional stability. The results indicated that mother phubbing was positively related to cyberbullying, which was mediated by perceived mother acceptance. Further, moderated mediation analyses showed that emotional stability moderated the direct path between mother phubbing and cyberbullying and the indirect path between mother phubbing and perceived mother acceptance. This study highlighted the harmful impact of mother phubbing on adolescents by showing a positive association between mother phubbing and adolescent cyberbullying, as well as the underlying mechanisms between mother phubbing and adolescent cyberbullying.
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http://dx.doi.org/10.1177/0886260520983905DOI Listing
December 2020

Effects and Moderators of Computer-Based Training on Children's Executive Functions: A Systematic Review and Meta-Analysis.

Front Psychol 2020 26;11:580329. Epub 2020 Nov 26.

School of Psychology, Northeast Normal University, Changchun, China.

Computer-based training has attracted increasing attention from researchers in recent years. Several studies have found that computer-based training resulted in improved executive functions (EFs) in adults. However, it remains controversial whether children can benefit from computer-based training and what moderator could influence the training effects. The focus of the present meta-analysis was to examine the effects of computer-based training on EFs in children: working memory, cognitive flexibility, and inhibitory control. A thorough search of published work yielded a sample of 36 studies with 216 effect sizes. The results indicated that computer-based training showed moderate training effects on improving EFs in children ( = 0.35, = 36, < 0.001), while training effects of working memory were significantly higher. Furthermore, we found near-transfer effects were marginally significantly higher than far-transfer effects. The standard training method was significantly more effective than training with game elements. In computer-based training, typically developing children had significantly better training effects than atypically developing children. Some additional factors, such as the number of training sessions and age, also modulated the training effects. In conclusion, the present study investigated the effects and moderators of computer-based training for children's EFs. The results provided evidence that computer-based training (especially standard training) may serve as an efficient way to improve EFs in children (especially typically developing individuals). We also discussed some directions for future computer-based training studies.
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http://dx.doi.org/10.3389/fpsyg.2020.580329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726355PMC
November 2020

Self-esteem and cultural worldview buffer mortality salience effects on responses to self-face: Distinct neural mediators.

Biol Psychol 2020 09 15;155:107944. Epub 2020 Aug 15.

Faculty of Psychology, Center for Studies of Education and Psychology of Minorities in Southwest China, Southwest University, Chongqing, 400715, China. Electronic address:

Terror management theory proposes cultural worldview and self-esteem as two buffers against death anxiety. The neural mediators of these buffering effects, however, have not been fully understood. The present work investigated neural mediation mechanisms between self-esteem/cultural trait (self-construal) and mortality salience (MS) effects on self-face processing. We found that MS (vs. NA) priming eliminated self-face advantage in behavioral judgments of face-orientation in low self-esteem individuals and reduced self-face advantage in behavioral judgments of facial-familiarity in individuals with high interdependent self-construals. Our functional magnetic resonance imaging (fMRI) results showed that, following MS priming, insular activities mediated the relationship between self-esteem and self-face advantage in face-orientation judgments, whereas dorsal medial prefrontal activity mediated the relationship between interdependent self-construal and self-face advantage in face-familiarity judgments. Our findings suggest that distinct neural mechanisms are engaged in mediating the relationships between self-esteem/cultural trait and MS effects on the emotional and cognitive processes of self-relevant information.
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http://dx.doi.org/10.1016/j.biopsycho.2020.107944DOI Listing
September 2020

The Zika Virus Capsid Disrupts Corticogenesis by Suppressing Dicer Activity and miRNA Biogenesis.

Cell Stem Cell 2020 10 6;27(4):618-632.e9. Epub 2020 Aug 6.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Zika virus (ZIKV) causes microcephaly and disrupts neurogenesis. Dicer-mediated miRNA biogenesis is required for embryonic brain development and has been suggested to be disrupted upon ZIKV infection. Here we mapped the ZIKV-host interactome in neural stem cells (NSCs) and found that Dicer is specifically targeted by the capsid from ZIKV, but not other flaviviruses, to facilitate ZIKV infection. We identified a capsid mutant (H41R) that loses this interaction and does not suppress Dicer activity. Consistently, ZIKV-H41R is less virulent and does not inhibit neurogenesis in vitro or corticogenesis in utero. Epidemic ZIKV strains contain capsid mutations that increase Dicer binding affinity and enhance pathogenicity. ZIKV-infected NSCs show global dampening of miRNA production, including key miRNAs linked to neurogenesis, which is not observed after ZIKV-H41R infection. Together these findings show that capsid-dependent suppression of Dicer is a major determinant of ZIKV immune evasion and pathogenesis and may underlie ZIKV-related microcephaly.
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http://dx.doi.org/10.1016/j.stem.2020.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541724PMC
October 2020

Increased circulating total bile acid levels were associated with organ failure in patients with acute pancreatitis.

BMC Gastroenterol 2020 Jul 13;20(1):222. Epub 2020 Jul 13.

Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, People's Republic of China.

Background: Recent studies have shown that bile acids (BAs) are closely related to metabolic and inflammatory diseases. Our study aimed to investigate whether circulating total bile acid (TBA) levels were associated with the severity of acute pancreatitis (AP).

Methods: We retrospectively collected data on patients diagnosed with AP in a tertiary center from 01 January 2014 to 31 December 2016. The highest TBA value during the first 1,2,3,5,7 days after admission was determined as D1, D2, D3, D5, D7 TBA. Patients were divided into the high TBA (HTBA) group and the normal TBA (NTBA) group according to whether the TBA was ≥10 μmol/L. The prognosis and complications, including death, organ failure (OF) and pancreatic necrosis, were compared between the two groups. Logistic regression analysis and receiving operating characteristic (ROC) curve were used to evaluate the relationship between circulating TBA and organ failure in AP patients.

Results: Through stratified analysis of each time period, we found that the incidence of OF in the HTBA group was significantly higher than that in the NTBA group, and the AP severity classification in the HTBA group was more serious than that in the NTBA group. In addition, according to the D7 TBA values, the pancreatic necrosis rate, percutaneous catheter drainage (PCD) rate and mortality in the HTBA group were higher than those in the NTBA group. Multivariate regression analysis showed that HTBA (odds ratio (OR), 4.894; P = 0.002) was an independent risk factor for AP complicated with OF, which was verified in the grouping based on D7 TBA. ROC analysis revealed that a circulating D7 TBA cutoff point of 6.450 umol/L had optimal predictive value for the development of OF in AP patients with an area under the curve of the ROC curve (AUCROC) of 0.777.

Conclusions: The increase of circulating TBA in early stage of AP is independently related to organ failure, which indicates the adverse prognosis of AP patients.
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http://dx.doi.org/10.1186/s12876-020-01243-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359019PMC
July 2020

Selective Adsorption of Cationic Dyes for Stable Metal-Organic Framework ZJU-48.

ACS Omega 2020 Jun 4;5(23):13595-13600. Epub 2020 Jun 4.

School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. China.

A cationic metal-organic framework (MOF) ZJU-48 with one-dimensional pores of about 9.1 × 9.1 Å has been prepared from zinc ions, adenine, and carboxyl ligands. ZJU-48 displays excellent water stability for about one week, exhibiting its potential application for adsorption and separation of dyes. Cationic and anionic dyes with similar sizes are adopted to study the adsorbing and separating properties of ZJU-48. Cationic dyes are adsorbed better than anionic dyes because of the negatively charged zeta potential of the material surface, implying its selective adsorption to cationic dyes, and it is charge-based adsorption. Meanwhile, the adsorption ability of the MOF to cationic dyes with different sizes is also investigated. We find that the adsorbed amount decreases with increase in the size of organics ,indicating that it is size-based adsorption. Furthermore, the cationic dye methylene blue (MB) is employed and focused on for its suitable charge and fitting size to evaluate the maximum adsorption capacity and desorption progress of ZJU-48. The results show that the maximum loaded amount of MOF toward MB reaches 582.44 mg/g, and about 90% of loaded dyes can be released from frameworks in ,-dimethylformamide with NaCl over 6 h, exhibiting satisfactory adsorptive property and possibility as a reusable adsorbent.
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http://dx.doi.org/10.1021/acsomega.0c00385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301382PMC
June 2020

Difficulties in Emotion Regulation and Cyberbullying Among Chinese Adolescents: A Mediation Model of Loneliness and Depression.

J Interpers Violence 2020 May 18:886260520917517. Epub 2020 May 18.

Renmin University of China, Beijing, China.

Recent research has ascertained some risk factors for cyberbullying. However, few studies have investigated the potential influence of difficulties in emotion regulation (DER) on cyberbullying, and there is little knowledge about the mediating mechanisms underlying this association. This study investigated whether DER would be significantly related to adolescent cyberbullying and whether loneliness and depression would sequentially mediate the link between DER and adolescent cyberbullying. A sample of 719 Chinese middle school students completed measures regarding demographics, DER, loneliness, depression, and cyberbullying. After controlling for the demographic covariates, the results showed that (a) DER was positively associated with adolescent cyberbullying; (b) loneliness and depression sequentially mediated the relation between DER and adolescent cyberbullying. This study emphasizes the underlying mediating mechanisms between DER and adolescent cyberbullying, which is of great significance for the prevention and intervention of adolescent cyberbullying in the digital age.
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http://dx.doi.org/10.1177/0886260520917517DOI Listing
May 2020

Parental phubbing accelerates depression in late childhood and adolescence:A two-path model.

J Adolesc 2020 01 9;78:43-52. Epub 2019 Dec 9.

School of Business, Central South University, Changsha, 410083, China. Electronic address:

Introduction: Phubbing is a social exclusion behavior related to mobile phone use. It undermines interpersonal relationships and mental health. This study aimed to test the connections between parental phubbing and depression in late childhood and adolescence, as well as the mediating roles of parental warmth, parental rejection, and relatedness need satisfaction.

Methods: We conducted two studies. Study 1 was a cross-sectional study of 530 Chinese students (268 boys and 262 girls, M = 13.15 ± 0.64 years) who completed self-report questionnaires. We conducted structural modeling to test the relationship between parental phubbing and depression. Study 2 used a short longitudinal design to validate the results of Study 1 and test the mediating roles of parental warmth, parental rejection, and relatedness need satisfaction. In Study 2, we recruited 293 Chinese students (151 boys, 141 girls, and one participant with no reported gender information, M = 12.87 ± 0.74 years) to complete the questionnaires and applied structural equation modeling to analyze the data.

Results: Two sequential mediation effects were found. The first was parental phubbing → parental warmth → relatedness need satisfaction → depression (protection-reduced effect). The second was parental phubbing → parental rejection → relatedness need satisfaction → depression (risk-increased effect). Gender differences were non-significant.

Conclusions: The study revealed that parental phubbing was associated with students' depression in late childhood and adolescence through two paths. The present study highlights the need to establish family norms regulating mobile phone use to reduce phubbing.
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http://dx.doi.org/10.1016/j.adolescence.2019.12.004DOI Listing
January 2020

Deviant Peer Affiliation and Bullying Perpetration in Adolescents: The Mediating Role of Moral Disengagement and the Moderating Role of Moral Identity.

J Psychol 2020 9;154(3):199-213. Epub 2019 Dec 9.

Renmin University of China.

Based on the integration of the group socialization theory and the individual-context interaction model, we examined whether moral disengagement mediated the association between deviant peer affiliation and bullying perpetration and whether this mediation model was moderated by moral identity. A total of 438 adolescents participated in the current study. They completed measures regarding deviant peer affiliation, bullying perpetration, moral disengagement, and moral identity. Deviant peer affiliation positively predicted adolescents' bullying perpetration at six months later and this relationship was partially mediated by moral disengagement. Moral identity did not moderate the direct relationship between deviant peer affiliation and adolescents' bullying perpetration. Moral identity moderated the relationship between moral disengagement and adolescents' bullying perpetration and in turn moderated the indirect relationship between deviant peer affiliation and bullying perpetration. Specifically, the relationship between moral disengagement and bullying perpetration and the indirect relationship between deviant peer affiliation and bullying perpetration moral disengagement both became nonsignificant for adolescents with high moral identity.
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http://dx.doi.org/10.1080/00223980.2019.1696733DOI Listing
July 2020

NQDI-1 protects against acinar cell necrosis in three experimental mouse models of acute pancreatitis.

Biochem Biophys Res Commun 2019 11 3;520(1):211-217. Epub 2019 Oct 3.

Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China. Electronic address:

NQDI-1, an inhibitor of ASK1, has been reported to have protective effects in several experimental human disease models. However, the role of NQDI-1 in acute pancreatitis (AP) has not been reported. In this study, we found that NQDI-1 could attenuate histological damage of pancreatic tissue as well as the levels of serum amylase and lipase in a mouse model of AP induced by caerulein. Moreover, the production of reactive oxygen species (ROS) and the expression of necrosis-related proteins (RIP3 and p-MLKL) were also reduced after NQDI-1 administration. Correspondingly, we elucidated the effect of NQDI-1 in vitro and found that NQDI-1 protected against pancreatic acinar cells necrosis via decreasing the ROS production and RIP3 and p-MLKL expression. In addition, we identified the protective effect of NQDI-1 on AP through two other mouse models induced by l-arginine and pancreatic duct ligation. Taken together, these findings showed that NQDI-1 could reduce the acinar cells necrosis and alleviate the severity of AP, which may afford a new therapeutic target on pancreatic necrosis in AP clinically.
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http://dx.doi.org/10.1016/j.bbrc.2019.09.125DOI Listing
November 2019

Electrochemical behavior of CoCrMo alloy for dental applications in acidic artificial saliva containing albumin.

Colloids Surf B Biointerfaces 2019 Dec 6;184:110492. Epub 2019 Sep 6.

Ministryof Education Key Laboratory of Green Preparation and Application for Functional Materials, Hubei University, Wuhan, 430062, PR China.

The electrochemical properties of CoCrMo alloy immersed in different artificial saliva with or without Ca and albumin were studied by open circuit potential (OCP), electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PP), and meanwhile the microstructures features, phase identification and chemical composition of the alloy were analyzed by SEM, EDS, XRD and RA-IR to further understand the electrochemical behavior of the alloy. The results indicated that the self-passivation behavior of the alloy occurred universally and was obviously distinct with each other in different acidic artificial saliva. No phase transformation was observed and the oxide layer and corrosion products exhibited amorphous nature. There was an obvious complexation of the adsorbed albumin with the alloy, and the adsorption capacity of albumin increased with the prolongation of immersion time. The adsorbed albumin presenting black stripped spots had a certain inhibition to the formation of passivation film, and Ca in saliva promoted the further adsorption of albumin as an intermediate bridge, going against the improvement of the corrosion resistance of passivation film/alloy system. In addition, the passivation state of the alloy surface was changed by different methods to investigate the adsorption behavior of albumin and its influence on the further passivation behavior in depth. Hitherto, we tried to propose a model to explain the dynamic adsorption process of albumin and its influencing mechanism on the growth behavior of passivation film.
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http://dx.doi.org/10.1016/j.colsurfb.2019.110492DOI Listing
December 2019

Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss.

Nat Neurosci 2019 07 24;22(7):1089-1098. Epub 2019 Jun 24.

Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Pericytes are positioned between brain capillary endothelial cells, astrocytes and neurons. They degenerate in multiple neurological disorders. However, their role in the pathogenesis of these disorders remains debatable. Here we generate an inducible pericyte-specific Cre line and cross pericyte-specific Cre mice with iDTR mice carrying Cre-dependent human diphtheria toxin receptor. After pericyte ablation with diphtheria toxin, mice showed acute blood-brain barrier breakdown, severe loss of blood flow, and a rapid neuron loss that was associated with loss of pericyte-derived pleiotrophin (PTN), a neurotrophic growth factor. Intracerebroventricular PTN infusions prevented neuron loss in pericyte-ablated mice despite persistent circulatory changes. Silencing of pericyte-derived Ptn rendered neurons vulnerable to ischemic and excitotoxic injury. Our data demonstrate a rapid neurodegeneration cascade that links pericyte loss to acute circulatory collapse and loss of PTN neurotrophic support. These findings may have implications for the pathogenesis and treatment of neurological disorders that are associated with pericyte loss and/or neurovascular dysfunction.
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http://dx.doi.org/10.1038/s41593-019-0434-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668719PMC
July 2019

Cyberbullying and depression among Chinese college students: A moderated mediation model of social anxiety and neuroticism.

J Affect Disord 2019 09 27;256:54-61. Epub 2019 May 27.

Department of Applied Psychology in College of Psychiatry, Wenzhou Medical University, Wenzhou 325035, China. Electronic address:

Background: Cyberbullying is a serious social issue that can cause a number of psychological and behavioral problems for perpetrators and victims. Previous studies have shown that adolescent victims of cyberbullying are more likely to exhibit depressive symptoms. However, few studies have investigated the relationship between the perpetration of cyberbullying and depression, or the mediating and moderating mechanisms underlying this relationship.

Methods: A questionnaire survey was conducted among 476 college students to investigate the relationships between cyberbullying perpetration and depression, the mediating role of social anxiety, and the moderating role of neuroticism.

Results: The results showed that cyberbullying perpetration had a significant and positive predictive effect on depression. Social anxiety partially mediated this relationship. The direct predictive effect of cyberbullying perpetration on depression, and the relation between social anxiety and depression, were both moderated by neuroticism. Cyberbullying perpetration had a greater impact on depression for college students with lower levels of neuroticism and the predictive function of social anxiety on depression was stronger for individuals with low levels of neuroticism too. But neuroticism did not moderate the association between cyberbullying perpetration and social anxiety.

Limitations: This study focused only on the individual variables influencing the relationship between cyberbullying perpetration and depression, and did not examine interpersonal or environmental variables. Also, the cross-sectional research design means that causality cannot be deduced from the results.

Conclusions: Cyberbullying perpetration can predict depression directly, and also indirectly via the mediating role of social anxiety. Neuroticism moderates the relation both between cyberbullying and depression, and between social anxiety and depression. These findings provide new perspectives for the treatment and prevention of depression among college students.
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http://dx.doi.org/10.1016/j.jad.2019.05.061DOI Listing
September 2019

TRIM9-Mediated Resolution of Neuroinflammation Confers Neuroprotection upon Ischemic Stroke in Mice.

Cell Rep 2019 04;27(2):549-560.e6

Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address:

Excessive and unresolved neuroinflammation is a key component of the pathological cascade in brain injuries such as ischemic stroke. Here, we report that TRIM9, a brain-specific tripartite motif (TRIM) protein, was highly expressed in the peri-infarct areas shortly after ischemic insults in mice, but expression was decreased in aged mice, which are known to have increased neuroinflammation after stroke. Mechanistically, TRIM9 sequestered β-transducin repeat-containing protein (β-TrCP) from the Skp-Cullin-F-box ubiquitin ligase complex, blocking IκBα degradation and thereby dampening nuclear factor κB (NF-κB)-dependent proinflammatory mediator production and immune cell infiltration to limit neuroinflammation. Consequently, Trim9-deficient mice were highly vulnerable to ischemia, manifesting uncontrolled neuroinflammation and exacerbated neuropathological outcomes. Systemic administration of a recombinant TRIM9 adeno-associated virus that drove brain-wide TRIM9 expression effectively resolved neuroinflammation and alleviated neuronal death, especially in aged mice. These findings reveal that TRIM9 is essential for resolving NF-κB-dependent neuroinflammation to promote recovery and repair after brain injury and may represent an attractive therapeutic target.
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http://dx.doi.org/10.1016/j.celrep.2018.12.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485958PMC
April 2019

Universality vs. Cultural Specificity in the Relations Among Emotional Contagion, Emotion Regulation, and Mood State: An Emotion Process Perspective.

Front Psychol 2019 12;10:186. Epub 2019 Feb 12.

Department of Psychology, Renmin University of China, Beijing, China.

To investigate the universality and cultural specificity of emotion processing in children from three different ethnic groups (Han, Jingpo, and Dai), we administered three questionnaires, including the emotional contagion scale, emotion regulation scale, and the Chinese mood adjective check list, to 1,362 ethnic Han, Dai, and Jingpo participants ( = 13.78 years). Structural equation modeling was used to examine the universality and cultural specificity in the relations among emotional contagion, emotion regulation, and mood state. The results revealed that emotion regulation mediated the relation between emotional contagion and mood state: positive emotional contagion increased positive mood state and decreased negative mood state by the mediated role of reappraisal, negative emotional contagion decreased positive contagion and increased negative mood state by the inconsistent mediated role of reappraisal; negative contagion increased negative mood state by the mediated role of suppression. We found both universality and cultural specificity in the relations among emotional contagion, emotion regulation, and mood state. Regarding cultural specificity, among Dai and Jingpo participants, negative contagion positively predicted reappraisal, while for Han participants, it did not; Jingpo participants demonstrated a weaker negative relation between reappraisal and negative mood state, and a stronger positive relation between negative contagion and suppression; and Dai participants were the only ethnic group that showed a negative connection between negative contagion and positive mood state. Regarding emotion universality, the three ethnic groups all showed positive relations between negative contagion and negative mood, and between suppression and negative mood; additionally, positive contagion positively predicted positive mood state, mediated by reappraisal. Thus, some emotion processes are universal and others more specific. In this paper, we discuss universal emotion processes and ethnic cultural differences in these emotion processes.
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http://dx.doi.org/10.3389/fpsyg.2019.00186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379289PMC
February 2019

How are smartphones associated with adolescent materialism?

J Health Psychol 2020 Nov-Dec;25(13-14):2406-2417. Epub 2018 Sep 19.

Renmin University of China, China.

This study examined whether smartphone addiction predicted adolescent materialism and whether self-esteem mediated the relation between smartphone addiction and adolescent materialism. Moreover, this study tested whether this mediating process was moderated by student-student relationship. Our theoretical model was tested among 748 middle school students in China (mean age = 16.80, standard deviation = .73). The results indicated that smartphone addiction was positively related to adolescent materialism. Mediation analysis showed that self-esteem mediated this relation. Moderated mediation test further revealed that the mediated path was moderated by student-student relationship.
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http://dx.doi.org/10.1177/1359105318801069DOI Listing
April 2021

Corrigendum to "Naringenin Protects against Acute Pancreatitis in Two Experimental Models in Mice by NLRP3 and Nrf2/HO-1 Pathways".

Mediators Inflamm 2018 29;2018:8621908. Epub 2018 Jul 29.

Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Clinical Medical College of Nanjing Medical University, No. 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, China.

[This corrects the article DOI: 10.1155/2018/3232491.].
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http://dx.doi.org/10.1155/2018/8621908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087586PMC
July 2018

Basic psychological needs satisfaction and fear of missing out: Friend support moderated the mediating effect of individual relative deprivation.

Psychiatry Res 2018 10 18;268:223-228. Epub 2018 Jul 18.

Department of Psychology & The Center of Internet + Social Psychology, Renmin University of China, Beijing 100872, China. Electronic address:

Fear of missing out (FOMO) is a new mental illness in digital era. Basing on the self-determination theory, the present study investigated how basic psychological needs satisfaction reducing FOMO. We tested a moderated mediating model that friend support moderated the mediating role of individual relative deprivation on the relation between basic psychological needs satisfaction and FOMO. A sample of 815 college students (mean age = 19.03 ± 1.13 years) participated our paper-and-pencil survey. Results showed that, basic psychological needs satisfaction negatively correlated with FOMO, and it reduced participants' FOMO via reducing individual relative deprivation. What's more, the mediating effect was moderated by friend support, comparing with low friend support participants, the indirect effect was larger among high friend support participants. The present study indicated that basic psychological needs satisfaction, and friend support were protective factors for college students' mental health. The limitations and implications were discussed.
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http://dx.doi.org/10.1016/j.psychres.2018.07.025DOI Listing
October 2018

Selfie posting and self-esteem among young adult women: A mediation model of positive feedback and body satisfaction.

J Health Psychol 2020 02 13;25(2):161-172. Epub 2018 Jul 13.

Department of Psychology, Renmin University of China, China.

This study examined whether selfie-posting was positively associated with women's self-esteem and whether this association was mediated by positive feedback and body satisfaction. A sample of 442 Chinese young adult women completed questionnaires on selfie-posting, positive feedback, body satisfaction, and self-esteem. Results indicated that selfie-posting was significantly and positively related to women's self-esteem. In addition, positive feedback mediated the relation between selfie-posting and women's self-esteem. Furthermore, the association between selfie-posting and self-esteem was sequentially mediated through positive feedback and body satisfaction. Findings from this study provide new insights into the relation between selfie-posting and self-esteem.
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http://dx.doi.org/10.1177/1359105318787624DOI Listing
February 2020

INT-777, a bile acid receptor agonist, extenuates pancreatic acinar cells necrosis in a mouse model of acute pancreatitis.

Biochem Biophys Res Commun 2018 09 7;503(1):38-44. Epub 2018 Jun 7.

Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address:

Bile acids receptor TGR5 and its agonist INT-777, which has been found to be involved in the NLRP3 inflammasome pathway, play an important role in inflammatory diseases. However, the role of INT-777 in acute pancreatitis (AP) has not been reported. In this present study, we found that TGR5 was expressed in pancreatic tissue and increased after AP onset induced by caerulein and further evaluated the impact of INT-777 on the severity of AP. The results showed that INT-777 could reduce the severity of AP in mice, which was manifested as decreased pancreatic tissue damage as well as the decrease of serum enzymes (amylase and lipase), pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and the expression of necrosis related proteins (RIP3 and p-MLKL). Furthermore, we found that INT-777 reduced the reactive oxygen species (ROS) production in pancreatic acinar cells and inhibited the activation of NLRP3 inflammasome pathway. In conclusion, our data showed that INT-777 could protect pancreatic acinar cell against necrosis and reduce the severity of AP, which may be mediated by inhibiting ROS/NLRP3 inflammasome pathway.
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http://dx.doi.org/10.1016/j.bbrc.2018.05.120DOI Listing
September 2018

Naringenin Protects against Acute Pancreatitis in Two Experimental Models in Mice by NLRP3 and Nrf2/HO-1 Pathways.

Mediators Inflamm 2018 8;2018:3232491. Epub 2018 Apr 8.

Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Clinical Medical College of Nanjing Medical University, No. 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, China.

Background: Naringenin (Nar) is a type of flavonoid and has been shown to have anti-inflammatory and antioxidative properties. However, the effects of Nar on acute pancreatitis (AP) have not been well studied. In this study, we aimed to investigate the function of Nar in a mouse model of AP.

Methods: Mild acute pancreatitis (MAP) was induced by caerulein (Cae), and severe acute pancreatitis (SAP) was induced by L-arginine in mice. Nar was administered intraperitoneally at doses of 25, 50, or 100 mg/kg following MAP induction and at a dose of 100 mg/kg following SAP induction. The serum levels of cytokines, lipase, and amylase were determined, and pancreatic and pulmonary tissues were harvested.

Results: The serum levels of amylase, lipase, and cytokines were significantly decreased in both MAP and SAP models after Nar treatment. The malondialdehyde (MDA) levels of the pancreatic tissue was significantly reduced in both MAP and SAP after Nar treatment. In contrast, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), total sulfhydryl (T-SH), and non-proteinsulthydryl (NP-SH) were markedly increased in both MAP and SAP after Nar treatment. The injury in pancreatic and pulmonary tissues was markedly improved as evidenced by the inhibited expression of myeloperoxidase, nod-like receptor protein 3, and interleukin 1 beta as well as the enhanced expression of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 in pancreatic tissues.

Conclusions: Nar exerted protective effects on Cae-induced MAP and L-arginine-induced SAP in mice, suggesting that Nar may be a potential therapeutic intervention for AP.
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http://dx.doi.org/10.1155/2018/3232491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911315PMC
October 2018

Sleep quality as a mediator of problematic smartphone use and clinical health symptoms.

J Behav Addict 2018 Jun 23;7(2):466-472. Epub 2018 May 23.

3 Faculty of Psychology, Southwest University , Chongqing, China.

Background and aims Although smartphone use brings many benefits for adolescents, it is also associated with many serious health problems. This study examined the relationship between problematic smartphone use (PSU) and clinical health symptoms (e.g., body dysfunction) and the mediating effects of sleep quality on this relationship in adolescents. Methods Participants in this cross-sectional survey were 686 middle- and high-school students (girls = 55.7%, M = 12.98 ± 1.38 years). Participants completed self-report measures of PSU, sleep quality, and physical symptoms. Correlation analyses and structural equation modeling between adolescents' PSU and the variables of interest were conducted. Results This study indicated that there was a significant positive correlation between PSU and health symptoms. Furthermore, sleep quality mediated the relationship between PSU and health symptoms. Discussion and conclusions Findings suggest that to promote health and wellness in adolescents, individuals should be encouraged to place boundaries on smartphone use, especially at bedtime. Reducing adolescents' exposure to smartphone use in this way may hold promise for improving the efficacy of PSU prevention efforts for adolescents.
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http://dx.doi.org/10.1556/2006.7.2018.40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174583PMC
June 2018

Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis by possible reduction of NLRP3 activation and up-regulation of NET expression.

Biochem Biophys Res Commun 2018 01 19;495(4):2439-2447. Epub 2017 Dec 19.

Surgical Intensive Care Unit, Department of General Surgery, Jinling Clinical Medical College of Nanjing Medical University, No. 305 Zhongshan East Road, Nanjing 210002, Jiangsu Province, China. Electronic address:

Objective: Previous studies have shown that acute inflammation is associated with increased sympathetic activity, which in turn increases the inflammatory response and leads to organ damage. The present study aimed to investigate whether dexmedetomidine administration during acute pancreatitis (AP) lessens pancreatic pathological and functional injury and the inflammatory response, and to explore the underlying mechanisms.

Methods: Mild pancreatitis was induced in mice with caerulein, and severe pancreatitis was induced with caerulein plus lipopolysaccharide (LPS). After pancreatitis induction, dexmedetomidine at 10 or 20 μg/kg was injected via the tail vein. Pancreatic pathological and functional injury was assessed by histology and serum levels of amylase and lipase, respectively. The inflammatory response was evaluated by determining serum levels of inflammatory factors. The expression of myeloperoxidase (MPO) was examined by immunohistochemistry. The expression of norepinephrine transporter (NET), NLRP3, pro-IL-1β, and interleukin (IL)-1β in pancreatic tissue was detected by Western blot and real-time PCR.

Results: Dexmedetomidine at 20 μg/kg significantly attenuated pancreatic pathological injury, reduced serum levels of amylase, lipase, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and decreased the expression of MPO in pancreatic tissue in both mouse models of pancreatitis. In addition, dexmedetomidine at 20 μg/kg significantly down-regulated the expression of NLRP3, pro-IL-1β, and IL-1β in pancreatic tissue, but up-regulated the expression of NET in both mouse models.

Conclusion: Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis possibly by reducing NLRP3 activation and up-regulating NET expression.
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http://dx.doi.org/10.1016/j.bbrc.2017.12.090DOI Listing
January 2018

Peer relationship and adolescent smartphone addiction: The mediating role of self-esteem and the moderating role of the need to belong.

J Behav Addict 2017 Dec 19;6(4):708-717. Epub 2017 Dec 19.

1 Department of Psychology, The Center of Internet + Social Psychology, Renmin University of China , Beijing, China.

Background and aims Adolescent smartphone addiction has received increased attention in recent years, and peer relationship has been found to be a protective factor in adolescent smartphone. However, little is known about the mediating and moderating mechanisms underlying this relation. The aim of this study was to investigate (a) the mediating role of self-esteem in the association between student-student relationship and smartphone addiction, and (b) the moderating role of the need to belong in the indirect relationship between student-student relationship and adolescent smartphone addiction. Methods This model was examined with 768 Chinese adolescents (mean age = 16.81 years, SD = 0.73); the participants completed measurements regarding student-student relationship, self-esteem, the need to belong, and smartphone addiction. Results The correlation analyses indicated that student-student relationship was significantly negatively associated with adolescent smartphone addiction, and the need to belong was significantly positively associated with adolescent smartphone addiction. Mediation analyses revealed that self-esteem partially mediated the link between student-student relationship and adolescent smartphone addiction. Moderated mediation further indicated that the mediated path was weaker for adolescents with lower levels of the need to belong. Discussion and conclusion High self-esteem could be a protective factor against smartphone addiction for adolescents with a strong need to belong as these students appeared to be at elevated risk of developing smartphone addiction.
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http://dx.doi.org/10.1556/2006.6.2017.079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034960PMC
December 2017

Viewing Fantastical Events Versus Touching Fantastical Events: Short-Term Effects on Children's Inhibitory Control.

Child Dev 2018 01 7;89(1):48-57. Epub 2017 May 7.

Zhejiang University.

Three pretest-posttest experiments were conducted to compare the effects of viewing versus interacting with either fantastical or real events on 4- and 6-year-old children's inhibitory control. Experiment 1 (N = 72) suggested that although viewing fantastical events had a negative effect on inhibitory control, interacting with them produced no such disruption. Experiment 2 (N = 17) also found that children's inhibitory control decreased after viewing fantastical events but not after interacting with them. In addition, functional near-infrared spectroscopy (fNIRS) data showed that viewing fantastical events resulted in greater activation in the dorsolateral prefrontal cortex. Experiment 3 (N = 72) showed that children's inhibitory control increased after viewing and interacting with real events. The implications for studying the effects of mobile devices are discussed.
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http://dx.doi.org/10.1111/cdev.12820DOI Listing
January 2018

Foot-and-mouth disease virus low-fidelity polymerase mutants are attenuated.

Arch Virol 2014 Oct 3;159(10):2641-50. Epub 2014 Jun 3.

Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin, 150001, P. R. China.

Previous studies have shown that RNA viruses can be attenuated by either increased or decreased viral polymerase replication fidelity. Although foot-and-mouth disease virus (FMDV) high-fidelity RNA-dependent RNA polymerase (RdRp) variants with an attenuated phenotype have been isolated using mutagens, no FMDV mutant with a low-fidelity polymerase has been documented to date. Here, we describe the generation of several FMDV RdRp mutants using site-directed mutagenesis via a reverse genetic system. Mutation frequency assays confirmed that five rescued FMDV RdRp mutant populations had lower replication fidelity than the wild-type virus population, which allowed us to assess the effects of the change in replication fidelity on the virus phenotype. These low-fidelity FMDV RdRp mutants showed increased sensitivity to ribavirin or 5-fluorouracil (5-FU) treatment without a loss of growth capacity in cell cultures. In addition, decreased fitness and attenuated virulence were observed for the RdRp mutants with lower fidelity. Importantly, based on a quantitative analysis for fidelity and virulence, we concluded that lower replication fidelity is associated with a more attenuated virus phenotype. These results further contribute to our understanding of the replication fidelity of polymerases of RNA viruses and its relationship to virulence attenuation.
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http://dx.doi.org/10.1007/s00705-014-2126-zDOI Listing
October 2014

Ribavirin-resistant variants of foot-and-mouth disease virus: the effect of restricted quasispecies diversity on viral virulence.

J Virol 2014 Apr 22;88(8):4008-20. Epub 2014 Jan 22.

Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.

Unlabelled: Mutagenic nucleoside analogues can be used to isolate RNA virus high-fidelity RNA-dependent RNA polymerase (RdRp) variants, the majority of which are attenuated in vivo. However, attenuated foot-and-mouth disease virus (FMDV) high-fidelity RdRp variants have not been isolated, and the correlations between RdRp fidelity and virulence remain unclear. Here, the mutagen ribavirin was used to select a ribavirin-resistant population of FMDV, and 4 amino acid substitutions (D5N, A38V, M194I, and M296V) were identified in the RdRp-coding region of the population. Through single or combined mutagenesis using a reverse genetics system, we generated direct experimental evidence that the rescued D5N, A38V, and DAMM mutants but not the M194I and M296V mutants are high-fidelity RdRp variants. Mutagen resistance assays revealed that the higher replication fidelity was associated with higher-level resistance to ribavirin. In addition, significantly attenuated fitness and virulence phenotypes were observed for the D5N, A38V, and DAMM mutants. Based on a systematic quantitative analysis of fidelity and virulence, we concluded that higher replication fidelity is associated with a more attenuated virus. These data suggest that the resulting restricted quasispecies diversity compromises the adaptability and virulence of an RNA virus population. The modulation of replication fidelity to attenuate virulence may represent a general strategy for the rational design of new types of live, attenuated vaccine strains.

Importance: The ribavirin-isolated poliovirus (PV) RdRp G64S variant, the polymerases of which were of high replication fidelity, was attenuated in vivo. It has been proposed (M. Vignuzzi, E. Wendt, and R. Andino, Nat. Med. 14:154-161, http://dx.doi.org/10.1038/nm1726) that modulation of replication fidelity is a promising approach for engineering attenuated virus vaccines. The subsequently mutagen-isolated RdRp variants also expressed the high-fidelity polymerase, but not all of them were attenuated. Few studies have shown the exact correlation between fidelity and virulence. The present study investigates the effect of restricted quasispecies diversity on viral virulence via several attenuated FMDV high-fidelity RdRp variants. Our findings may aid in the rational design of a new type of vaccine strain.
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http://dx.doi.org/10.1128/JVI.03594-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993757PMC
April 2014

An increased replication fidelity mutant of foot-and-mouth disease virus retains fitness in vitro and virulence in vivo.

Antiviral Res 2013 Oct 20;100(1):1-7. Epub 2013 Jul 20.

Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin 150001, PR China.

In a screen for RNA mutagen-resistant foot-and-mouth disease virus (FMDV) strains, we isolated an FMDV mutant with RNA-dependent RNA polymerase (RdRp) R84H substitution. This mutant, selected under the mutagenic pressure of 5-fluorouracil (5-FU), is resistant not only to 5-FU but also to other two RNA mutagens, 5-azacytidine and ribavirin, suggesting that the RdRp R84H mutant is a high fidelity variant. Subsequently, the increased fidelity of this mutant was verified through analysis of mutation frequency, which revealed a 1.4-fold enhancement in RdRp fidelity compared with the wild-type virus. Further studies indicated that the R84H mutant exhibited slightly increased fitness in vitro, and its virulence was not reduced in suckling mice. These results indicated that an increase in RdRp fidelity does not always correlate with reduced virus fitness and virus attenuation. Thus, this isolated R84H mutant provides a new platform to examine the evolutionary dynamics of fidelity-changing RNA viruses, such as mutagen resistance, fitness and virulence.
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http://dx.doi.org/10.1016/j.antiviral.2013.07.008DOI Listing
October 2013