ZBTB20 Regulates SERCA2a Activity and Myocardial Contractility Through Phospholamban.

BACKGROUND: Intracellular Ca2+ cycling determines myocardial contraction and relaxation in response to physiological demands. SERCA2a (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a) is responsible for the sequestration of cytosolic Ca2+ into intracellular stores during cardiac relaxation, and its activity is reversibly inhibited by PLN (phospholamban). However, the regulatory hierarchy of SERCA2a activity remains unclear. METHODS: Cardiomyocyte-specific ZBTB20 knockout mice were generated by crossing ZBTB20flox mice with Myh6-Cre mice. Echocardiography, blood pressure measurements, Langendorff perfusion, histological analysis and immunohistochemistry, quantitative reverse transcription-PCR, Western blot analysis, electrophysiological measurements, and chromatin immunoprecipitation assay were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: Specific ablation of ZBTB20 in cardiomyocyte led to a significant increase in basal myocardial contractile parameters both in vivo and in vitro, accompanied by an impairment in cardiac reserve and exercise capacity. Moreover, the cardiomyocytes lacking ZBTB20 showed an increase in sarcoplasmic reticular Ca2+ content and exhibited a remarkable enhancement in both SERCA2a activity and electrically stimulated contraction. Mechanistically, PLN expression was dramatically reduced in cardiomyocytes at the mRNA and protein levels by ZBTB20 deletion or silencing, and PLN overexpression could largely restore the basal contractility in ZBTB20-deficient cardiomyocytes. CONCLUSIONS: These data point to ZBTB20 as a fine-tuning modulator of PLN expression and SERCA2a activity, thereby offering new perspective on the regulation of basal contractility in the mammalian heart.

ZBTB20 is essential for cochlear maturation and hearing in mice.

The mammalian cochlear epithelium undergoes substantial remodeling and maturation before the onset of hearing. However, very little is known about the transcriptional network governing cochlear late-stage maturation and particularly the differentiation of its lateral nonsensory region. Here, we establish ZBTB20 as an essential transcription factor required for cochlear terminal differentiation and maturation and hearing. ZBTB20 is abundantly expressed in the developing and mature cochlear nonsensory epithelial cells, with transient expression in immature hair cells and spiral ganglion neurons. Otocyst-specific deletion of Zbtb20 causes profound deafness with reduced endolymph potential in mice. The subtypes of cochlear epithelial cells are normally generated, but their postnatal development is arrested in the absence of ZBTB20, as manifested by an immature appearance of the organ of Corti, malformation of tectorial membrane (TM), a flattened spiral prominence (SP), and a lack of identifiable Boettcher cells. Furthermore, these defects are related with a failure in the terminal differentiation of the nonsensory epithelium covering the outer border Claudius cells, outer sulcus root cells, and SP epithelial cells. Transcriptome analysis shows that ZBTB20 regulates genes encoding for TM proteins in the greater epithelial ridge, and those preferentially expressed in root cells and SP epithelium. Our results point to ZBTB20 as an essential regulator for postnatal cochlear maturation and particularly for the terminal differentiation of cochlear lateral nonsensory domain.

The zinc finger and BTB domain containing protein ZBTB20 regulates plasma triglyceride metabolism by repressing lipoprotein lipase gene transcription in hepatocytes.

BACKGROUND AND AIMS: Lipoprotein lipase (LPL) is responsible for the lipolytic processing of triglyceride-rich lipoproteins, the deficiency of which causes severe hypertriglyceridemia. Liver LPL expression is high in suckling rodents but relatively low at adulthood. However, the regulatory mechanism and functional significance of liver LPL expression are incompletely understood. We have established the zinc finger protein ZBTB20 as a critical factor for hepatic lipogenesis. Here, we evaluated the role of ZBTB20 in regulating liver Lpl gene transcription and plasma triglyceride metabolism. APPROACH AND RESULTS: Hepatocyte-specific inactivation of ZBTB20 in mice led to a remarkable increase in LPL expression at the mRNA and protein levels in adult liver, in which LPL protein was mainly localized onto sinusoidal epithelial cells and Kupffer cells. As a result, the LPL activity in postheparin plasma was substantially increased, and postprandial plasma triglyceride clearance was significantly enhanced, whereas plasma triglyceride levels were decreased. The dysregulated liver LPL expression and low plasma triglyceride levels in ZBTB20-deficient mice were normalized by inactivating hepatic LPL expression. ZBTB20 deficiency protected the mice against high-fat diet-induced hyperlipidemia without causing excessive triglyceride accumulation in the liver. Chromatin immunoprecipitation and gel-shift assay studies revealed that ZBTB20 binds to the LPL promoter in the liver. A luciferase reporter assay revealed that ZBTB20 inhibits the transcriptional activity of LPL promoter. The regulation of LPL expression by ZBTB20 is liver-specific under physiological conditions. CONCLUSIONS: Liver ZBTB20 serves as a key regulator of LPL expression and plasma triglyceride metabolism and could be a therapeutic target for hypertriglyceridemia.

MiR-19b-3p Inhibits Hypoxia-Ischemia Encephalopathy by Inhibiting SOX6 Expression via Activating Wnt/ß-catenin Pathway.

Hypoxic-ischemic encephalopathy (HIE) is a detrimental factor in infant death and chronic disease. The specific pathogenesis is not entirely clear. Therefore, exploring the pathogenesis of HIE is critical. The expression of miR-19b-3p and SOX6 in umbilical blood of HIE patients was detected by qRT-PCR assay. HT22 cells were triggered with oxygen-glucose deprivation/reoxygenation (OGD/R) to construct the HIE cell model. Cell Counting Kit-8 (CCK-8) assay was used to estimate viability. SOD and MDA levels were detected by enzyme linked immunosorbent assay. Flow cytometry was implemented to ascertain neurocyte apoptosis. Cellular ß-catenin immunofluorescence staining was used to detect the expression and distribution of ß-catenin protein. Wnt signaling pathway activation was detected by TOPFlash/FOPFlash luciferase reporter assay. The targeting correlation of SOX6 and miR-19b-3p was corroborated by dual-luciferase reporter gene assay and RNA pull-down assay. MiR-19b-3p expression was once down-regulated, whilst SOX6 expression was up-regulated in HIE patients. MiR-19b-3p overexpression promoted cell proliferation, repressed cell apoptosis, oxidative stress response, and Wnt/ß-catenin pathway activation in OGD/R-triggered HT22 cells. MiR-19b-3p negatively regulated SOX6 expression. SOX6 knockdown improved OGD/R-triggered HT22 cells injury via Wnt/ß-catenin pathway activation. MiR-19b-3p overexpression suppressed OGD/R-triggered HT22 cell injury via inhibiting SOX6 expression via activating Wnt/ß-catenin pathway.

Zbtb20 deficiency causes cardiac contractile dysfunction in mice.

The zinc-finger protein ZBTB20 regulates development and metabolism in multiple systems, and is essential for postnatal survival in mice. However, its potential role in the cardiovascular system remains undefined. Here, we demonstrate that ZBTB20 is critically involved in the regulation of cardiac contractility and blood pressure in mice. At the age of 16 days, the relatively healthy Zbtb20-null mice exhibited hypotension without obvious change of heart rate or other evidence for heart failure. Moreover, Zbtb20 deletion led to a marked reduction in heart size, left ventricular wall thickness, and cell size of cardiomyocytes, which was largely proportional to the decreased body growth. Notably, echocardiographic and hemodynamic analyses showed that cardiac contractility was greatly impaired in the absence of ZBTB20. Mechanistically, ZBTB20 deficiency decreased cardiac ATP contents, and compromised the enzyme activity of mitochondrial complex I in heart as well as L-type calcium current density in cardiomyocytes. Furthermore, the developmental activation of some mitochondrial function-related genes was significantly attenuated in Zbtb20-null myocardium, which included Hspb8, Ckmt2, Cox7a1, Tfrc, and Ogdhl. Put together, these results suggest that ZBTB20 plays a crucial role in the regulation of heart development, energy metabolism, and contractility.

Roles of Psychosocial Factors on the Association Between Online Social Networking Use Intensity and Depressive Symptoms Among Adolescents: Prospective Cohort Study.

BACKGROUND: The potential mechanisms underlying the association between online social networking use intensity and depressive symptoms are unclear and underresearched. OBJECTIVE: We aimed to investigate the potential roles of interpersonal psychosocial factors on the association between online social networking use intensity and depressive symptoms among early adolescents. METHODS: A total of 4237 adolescents from a 9-month longitudinal study were included. Score changes (indicated as △) for the social function use intensity (SFUI) and entertainment function use intensity (EFUI) subscales of the Online Social Networking Activity Intensity Scale and for friendship quality, perceived family support, perceived friend support, parent-adolescent conflict, social nonconfidence, and depressive symptoms were analyzed. The potential mediation effects of unfavorable psychosocial factors and suppression effects of favorable psychosocial factors on the association of △SFUI with △CES-D and the association of △EFUI with △CES-D were tested using hierarchical regression models. RESULTS: The association between △SFUI and △CES-D was partially mediated by △mother-adolescent conflict (mediation effect size 5.11%, P=.02) and △social nonconfidence (mediation effect size 20.97%, P<.001) but partially suppressed by △friendship quality, △perceived family support, and △perceived friend support, with suppression effects of -0.011 (P=.003), -0.009 (P=.003), and -0.022 (P<.001), respectively. The association between △EFUI and △CES-D was partially mediated by △social nonconfidence (mediation effect size 30.65%, P<.001) but partially suppressed by △perceived family support and △perceived friend support, with suppression effects of -0.036 (P<.001) and -0.039 (P<.001), respectively. CONCLUSIONS: The association between online social networking use intensity and depressive symptoms was partially mediated through the indirect increase in social nonconfidence and mother-adolescent conflict; however, better perceived social support and friendship quality would partially compensate for the harmful impact of online social networking use intensity on depressive symptoms among early adolescents.

The Relationship Between Caregiver Reactions and Psychological Distress in Family Caregivers of Patients With Heart Failure.

BACKGROUND: Providing care often causes negative reactions and psychological distress in family caregivers of patients with heart failure. How these 2 constructs are related has not been fully explored. OBJECTIVE: The aims of this study were to describe caregiver reactions to caregiving and psychological distress and to determine the associations between caregiver reactions to caregiving and psychological distress in family caregivers of patients with heart failure. METHODS: In this secondary analysis of a cross-sectional study, the sample included 231 patients and their family caregivers. The Chinese version of the Hospital Anxiety and Depression Scale was used to assess psychological distress (ie, symptoms of anxiety and depression), and the Caregiver Reaction Assessment was used to measure both negative and positive caregiver reactions to caregiving, including financial problems, impact on schedule, health problems, lack of family support, and self-esteem. RESULTS: Of the participants, 15.2% and 25.5% of caregivers reported symptoms of depression and anxiety, respectively. Impact on schedule was the most common caregiver reaction, followed by financial problems. Impact on schedule was related to both the caregivers' symptoms of depression (odds ratio [OR], 1.705; P = .001) and anxiety (OR, 1.306; P = .035), whereas financial problems were only related to symptoms of anxiety (OR, 1.273; P = .011). CONCLUSIONS: The findings suggest that interventions for reducing the negative impact on schedule of caregiving and helping to solve the caregivers' financial concerns might help to relieve their symptoms of depression and anxiety.

[Effect of acupuncture on early cerebral palsy infants with parafunctional sitting position: a multi-centre, randomized, control research].

OBJECTIVE: To study the clinical effect of development theory based acupuncture on early cerebral palsy (CP) infants with parafunctional sitting position. METHODS: Totally 120 early CP infants were randomly assigned to two groups equally, the treatment group and the control group. All received acupuncture combined with training rehabilitation. Patients in the treatment group adopted acupuncture based on infants development theory, while those in the control group were treated by head acupuncture. Sitting functional points in Gross motor function measure (GMFM) 88 were observed in different groups and infant patients of various types before and after treatment. Root mean square (RMS) signals of sitting correlated muscles (latissimus dorsi, erector spinae, rectus abdominis) were recorded by surface electromyography (sEMG). The effective rate was evaluated by Nimodipine method. RESULTS: Compared with before treatment, sitting functional points were significantly improved in the two groups (P<0.01). After treatment, it was higher in the treatment group than in the control group (P<0.01). The advance amplitude was higher in CP infants of the spastic type and the hypotonic type than other types (P<0.01). Along with sitting process, latissimus dorsi RMS signals were gradually tapered, erector spinae RMS signals were gradually enhanced, and rectus abdominis RMS signals were slightly weakened. Compared with the control group, latissimus dorsi RMS signals obviously decreased, and erector spinae RMS signals obviously increased in the treatment group after treatment (all P<0.01). The total effective rate was higher in the treatment group than in the control group (89.29% vs. 77.78%, P<0.05). CONCLUSION: Infants development theory based acupuncture could effectively elevate dorsi-extensor muscles force, improve sitting position of 8 months to 1 year old CP infants with parafunctional sitting position.

The effectiveness and safety of centralized early rehabilitation care for critically ill children with severe acquired brain injury: A retrospective cohort and implementation study.

BACKGROUND: Most children with neurocritical illness are at risk of physical, neurocognitive, and psychosocial sequelae and need centralized early rehabilitation care. OBJECTIVE: To identify the effectiveness and safety of centralized early rehabilitation care for children with severe acquired brain injury. METHODS: This is a mixed methods study-an implementation study and single-center retrospective cohort study with historical control. All children with severe acquired brain injury hospitalized in a specialized rehabilitation center in a comprehensive tertiary pediatric hospital between September 2016 and August 2020 were included. Patients treated in the centralized early rehabilitation unit were compared to historical controls dispersed in the normal inpatient rehabilitation ward. The effectiveness outcomes were measured by the Pediatric Cerebral Performance Category (PCPC) scale and the incidence of newly onset comorbidities. The safety outcomes were indicated by the mortality rate and the incidence of unexpected referrals. RESULTS: One hundred seventy-five patients were included. The delta PCPC scores of the first 4 weeks of inpatient rehabilitation in the intervention group were significantly lower than the control group (Z = -2.395, p = 0.017). The PCPC scores at 1 year in the intervention group were significantly reduced as compared to the control group (Z = -3.337, p = 0.001). The incidence of newly onset pneumonia/bronchitis was also decreased in the intervention group (χ2 = 4.517, p = 0.034). No death of patients was recorded, and there was no significant difference in unexpected referral rate between the two groups (χ2 = 0.374, p = 0.541). CONCLUSIONS: The centralized pediatrics early rehabilitation unit is effective and safe for children with severe acquired brain injury. Further multicenter prospective implementation studies on effectiveness, safety, and economic evaluation are needed.

[Construction and analysis of questionnaires on AIDS cough in traditional Chinese medicine diagnosis and treatment procedures].

OBJECTIVE: To norm the behavior of AIDS cough in traditional Chinese medicine diagnosis and treatment and improve the clinical level of cough treatment for HIV/AIDS, and build AIDS cough diagnosis and treatment procedures in traditional Chinese medicine. METHOD: Combined with clinical practice,to formulate questionnaire on AIDS cough in traditional Chinese medicine diagnosis and treatment by both English and Chinese literature research to expertise consultation and verify the results of the questionnaires on the statistics using the Delphi method. RESULT: Questionnaire contents consist of overview, pathogeny, diagnosis standard, dialectical medication (phlegm heat resistance pulmonary lung and kidney Yin deficiency lung spleen-deficiency), treating spleen-deficiency (lung), moxibustion treatment and aftercare care and diet and mental, average (2.93-3.00), full mark rate (93.10%-100%) ranks average (9.91-10.67) and (287.50-309.50) of which are the most high value, and the variation coefficient is 0.00, the Kendall coefficient (Kendalls W) is 0.049 which is statistical significance, the questionnaire reliability value of alpha was 0.788. CONCLUSION: Preliminary standarded concept, etiology and pathogenesis, diagnosis and syndrome differentiation treatment of AIDS cough, basically recognised by the experts in this field, and laid the foundation of traditional Chinese medicine diagnosis and treatment on develop the AIDS cough specifications.

Fructose overconsumption impairs hepatic manganese homeostasis and ammonia disposal.

Arginase, a manganese (Mn)-dependent enzyme, is indispensable for urea generation and ammonia disposal in the liver. The potential role of fructose in Mn and ammonia metabolism is undefined. Here we demonstrate that fructose overconsumption impairs hepatic Mn homeostasis and ammonia disposal in male mice. Fructose overexposure reduces liver Mn content as well as its activity of arginase and Mn-SOD, and impairs the clearance of blood ammonia under liver dysfunction. Mechanistically, fructose activates the Mn exporter Slc30a10 gene transcription in the liver in a ChREBP-dependent manner. Hepatic overexpression of Slc30a10 can mimic the effect of fructose on liver Mn content and ammonia disposal. Hepatocyte-specific deletion of Slc30a10 or ChREBP increases liver Mn contents and arginase activity, and abolishes their responsiveness to fructose. Collectively, our data establish a role of fructose in hepatic Mn and ammonia metabolism through ChREBP/Slc30a10 pathway, and postulate fructose dietary restriction for the prevention and treatment of hyperammonemia.

Associations of intensity and emotional connection related to online social networking use on the risk of incident depression among Chinese adolescents: A prospective cohort study.

OBJECTIVE: To investigate the longitudinal prediction of intensity and emotional connection (EC) related to online social networking use at baseline on the risk of incident depression at nine-month follow-up among adolescents. METHODS: A total of 3196 secondary school students, who were online social networking users and free of depression at baseline, were included in this study. Multilevel logistic regression models were applied to investigate the longitudinal prediction of two dimensions of online social networking use intensity (social function use intensity (SFUI), entertainment function use intensity (EFUI)) and EC scores at baseline on incident depression at follow-up. RESULTS: The incidence of depression was 23.37 per 100-person-years during a nine-month follow-up period. Baseline SFUI and EFUI scores were significantly associated with higher level of incident depression (adjusted OR = 1.017, 95% CI: 1.004-1.029 for SFUI, p = 0.010; adjusted OR = 1.046, 95% CI: 1.012-1.080 for EFUI, p = 0.007), after adjustment of significant background factors and baseline depressive symptom score. The associations of EC at baseline and its interaction with SFUI and EFUI on incident depression were statistically non-significant. CONCLUSION: Online social networking use seems be a risk factor of depression among adolescents, regardless of its specific functions. Early intervention is recommended to reduce the level of online social networking use intensity as a means of preventing depression among adolescents.

Classification of probable online social networking addiction: A latent profile analysis from a large-scale survey among Chinese adolescents.

BACKGROUND AND AIMS: Problematic online social networking use is prevalent among adolescents, but consensus about the instruments and their optimal cut-off points is lacking. This study derived an optimal cut-off point for the validated Online Social Networking Addiction (OSNA) scale to identify probable OSNA cases among Chinese adolescents. METHODS: A survey recruited 4,951 adolescent online social networking users. Latent profile analysis (LPA) and receiver operating characteristic curve (ROC) analyses were applied to the validated 8-item OSNA scale to determine its optimal cut-off point. RESULTS: The 3-class model was selected by multiple criteria, and validated in a randomly split-half subsample. Accordingly, participants were categorized into the low risk (36.4%), average risk (50.4%), and high risk (13.2%) groups. The highest risk group was regarded as "cases" and the rest as "non-cases", serving as the reference standard in ROC analysis, which identified an optimal cut-off point of 23 (sensitivity: 97.2%, specificity: 95.2%). The cut-off point was used to classify participants into positive (probable case: 17:0%) and negative groups according to their OSNA scores. The positive group (probable cases) reported significantly longer duration and higher intensity of online social networking use, and higher prevalence of Internet addiction than the negative group. CONCLUSIONS: The classification strategy and results are potentially useful for future research that measure problematic online social networking use and its impact on health among adolescents. The approach can facilitate research that requires cut-off points of screening tools but gold standards are unavailable.

Liver ChREBP Protects Against Fructose-Induced Glycogenic Hepatotoxicity by Regulating L-Type Pyruvate Kinase.

Excessive fructose consumption is closely linked to the pathogenesis of metabolic disease. Carbohydrate response element-binding protein (ChREBP) is a transcription factor essential for fructose tolerance in mice. However, the functional significance of liver ChREBP in fructose metabolism remains unclear. Here, we show that liver ChREBP protects mice against fructose-induced hepatotoxicity by regulating liver glycogen metabolism and ATP homeostasis. Liver-specific ablation of ChREBP did not compromise fructose tolerance, but rather caused severe transaminitis and hepatomegaly with massive glycogen overload in mice fed a high-fructose diet, while no obvious inflammation, cell death, or fibrosis was detected in the liver. In addition, liver ATP contents were significantly decreased by ChREBP deficiency in the fed state, which was rendered more pronounced by fructose feeding. Mechanistically, liver contents of glucose-6-phosphate (G6P), an allosteric activator of glycogen synthase, were markedly increased in the absence of liver ChREBP, while fasting-induced glycogen breakdown was not compromised. Furthermore, hepatic overexpression of LPK, a ChREBP target gene in glycolysis, could effectively rescue glycogen overload and ATP reduction, as well as mitigate fructose-induced hepatotoxicity in ChREBP-deficient mice. Taken together, our findings establish a critical role of liver ChREBP in coping with hepatic fructose stress and protecting from hepatotoxicity by regulating LPK.

Analysis of two pheromone-responsive conjugative multiresistance plasmids carrying the novel mobile optrA locus from Enterococcus faecalis.

Background: The acquired optrA gene, which encodes a ribosomal protection protein of the ABC-F family, can confer cross-resistance to linezolid and florfenicol, posing a serious therapeutic challenge to both human and veterinary medicine. Purpose: The objective of this study was to investigate the two Enterococcus faecalis (E. faecalis) plasmids for their fine structure, their transferability and the presence of mobile antimicrobial resistance loci. Methods: To elucidate their fine structure, the two plasmids were completely sequenced and the sequences analysed. Besides conjugation experiments, inverse PCR assays were conducted to see whether minicircles are produced from the mobile antimicrobial resistance loci. Results: Two pheromone-responsive conjugative optrA-carrying plasmids from E. faecalis, pE211 and pE508 were identified, which can transfer with frequencies of 2.6 ×10-2 and 3.7 ×10-2 (transconjugant per donor), respectively. In both plasmids, optrA was located on the novel mobile optrA locus with different sizes (12,834 bp in pE211 and 7,561 bp in pE508, respectively), flanked by two copies of IS1216 genes in the same orientation. Inverse PCR revealed that circular forms can be generated, consisting of optrA and one copy of IS1216, indicating they are all active. The 77,562 bp plasmid pE211 also carried Tn558 and a mobile bcrABDR locus, and the 84,468 bp plasmid pE508 also harbored the genes fexA, tet(L), tet(O/W/32/O) and a mobile aac(A)-aph(D) locus. Conclusion: The presence of mobile genetic elements in these plasmids renders them flexible and these elements will aid to the persistence and dissemination of these plasmids among enterococci and potentially also other gram-positive bacteria.

Melatonin suppresses TLR9-triggered proinflammatory cytokine production in macrophages by inhibiting ERK1/2 and AKT activation.

Toll-like receptor (TLR) signaling plays major roles in innate immune response in macrophages. Melatonin regulates TLR3- and TLR4-mediated innate immune responses in macrophages. However, it remains unknown whether melatonin regulates TLR9-mediated innate immune responses in macrophages. Here we demonstrated that melatonin suppressed TLR9 ligand-induced proinflammatory cytokines mRNA and protein production in peritoneal macrophages without interrupting the viability of peritoneal macrophages. Using a melatonin membrane receptors MT1/MT2 antagonist luzindole, we found that MT1 and MT2 were dispensable for melatonin's inhibitory effects on TLR9-mediated proinflammatory cytokines production, even though melatonin upregulated mRNA expression of MT1 and MT2 in macrophages. Furthermore, melatonin did not affect mRNA expressions of TLR9 and MyD88 but attenuated TLR9 ligand-induced ERK1/2 and AKT phosphorylation without affecting p38 and NF-κB p65 phosphorylation. Also, melatonin inhibited TLR9-mediated proinflammatory cytokines production in vivo. Taken together, our results demonstrate that melatonin suppresses TLR9-triggered proinflammatory cytokines production in macrophages via melatonin membrane receptor-independent manners and probably through inhibiting ERK1/2 and AKT activation, which further elucidates the roles of melatonin in regulating TLR-mediated innate immune responses in macrophages.

Online social networking addiction and depression: The results from a large-scale prospective cohort study in Chinese adolescents.

BACKGROUND AND AIMS: The aim of this study is to estimate the longitudinal associations between online social networking addiction (OSNA) and depression, whether OSNA predicts development of depression, and reversely, whether depression predicts development of OSNA. METHODS: A total of 5,365 students from nine secondary schools in Guangzhou, Southern China were surveyed at baseline in March 2014, and followed up 9 months later. Level of OSNA and depression were measured using the validated OSNA scale and CES-D, respectively. Multilevel logistic regression models were applied to estimate the longitudinal associations between OSNA and depression. RESULTS: Adolescents who were depressed but free of OSNA at baseline had 1.48 times more likely to develop OSNA at follow-up compared with those non-depressed at baseline [adjusted OR (AOR): 1.48, 95% confidence interval (CI): 1.14-1.93]. In addition, compared with those who were not depressed during the follow-up period, adolescents who were persistently depressed or emerging depressed during the follow-up period had increased risk of developing OSNA at follow-up (AOR: 3.45, 95% CI: 2.51-4.75 for persistent depression; AOR: 4.47, 95% CI: 3.33-5.99 for emerging depression). Reversely, among those without depression at baseline, adolescents who were classified as persistent OSNA or emerging OSNA had higher risk of developing depression compared with those who were no OSNA (AOR: 1.65, 95% CI: 1.01-2.69 for persistent OSNA; AOR: 4.29; 95% CI: 3.17-5.81 for emerging OSNA). CONCLUSION: The findings indicate a bidirectional association between OSNA and depression, meaning that addictive online social networking use is accompanied by increased level of depressive symptoms.

ZBTB20 regulates EGFR expression and hepatocyte proliferation in mouse liver regeneration.

Liver has a unique regenerative capacity, however, its regulatory mechanism is not fully defined. We have established the zinc-finger protein ZBTB20 as a key transcriptional repressor for alpha-fetoprotein (AFP) gene in liver. As a marker of hepatic differentiation, AFP expression is closely associated with hepatocyte proliferation. Unexpectedly, here we showed that ZBTB20 acts as a positive regulator of hepatic replication and is required for efficient liver regeneration. The mice specifically lacking ZBTB20 in hepatocytes exhibited a remarkable defect in liver regeneration after partial hepatectomy, which was characterized by impaired hepatocyte proliferation along with delayed cyclin D1 induction and diminished AKT activation. Furthermore, we found that epithelial growth factor receptor (EGFR) expression was dramatically reduced in the liver in the absence of ZBTB20, thereby substantially attenuating the activation of EGFR signaling pathway in regenerating liver. Adenovirus-mediated EGFR overexpression in ZBTB20-deficient hepatocytes could largely restore AKT activation in response to EGFR ligands in vitro, as well as hepatocyte replication in liver regeneration. Furthermore, ZBTB20 overexpression could significantly restore hepatic EGFR expression and cell proliferation after hepatectomy in ZBTB20-deficient liver. Taken together, our data point to ZBTB20 as a critical regulator of EGFR expression and hepatocyte proliferation in mouse liver regeneration, and may serve as a potential therapeutic target in clinical settings of liver regeneration.

Involvement of small G protein RhoB in the regulation of proliferation, adhesion and migration by dexamethasone in osteoblastic cells.

Long-term exposure to therapeutic doses of glucocorticoids (GCs) results in bone remodeling, which frequently causes osteoporosis and fracture healing retardation because of the abnormality of osteoblastic proliferation and differentiation. The mechanisms of GCs' effect on osteoblasts are largely unknown. In this present study, we found that dexamethasone (Dex) could induce the expression of the small G protein, RhoB, in mRNA and protein levels in the osteoblast-derived osteosarcoma cell lines MG-63. The up-regulation of RhoB mRNA by Dex mainly occurs at posttranscriptional level by increasing its mRNA stability through PI-3K/Akt and p38 mitogen-activated protein kinase signaling pathways. Over-expression of RhoB in MG-63 cells magnified while down-regulation of RhoB level by RNA interference impaired Dex-induced growth inhibition but not differentiation. What's more, over-expression of RhoB mimicked the effect of Dex on cell adhesion and migration. And interfering RhoB expression partially suppressed Dex-induced pro-adhesion and anti-migration in MG-63 cells. In conclusion, these results indicate that RhoB plays an important role in the pathological effect of Dex on osteoblastic growth and migration, which is a part of the mechanisms of GCs' adverse effect on bone remodeling.