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This three-wave longitudinal study aimed to investigate whether the relationship between self-control and academic achievement, through mastery goals, was conditional on the nature of the teacher-student relationships. A total of 852 junior school students in China completed questionnaires about self-control, mastery goals, and teacher-student relationships. Academic achievement was obtained from the school. The analyses of moderated mediation effects based on structural equation modeling showed that teacher-student emotional conflict increased the negative effect of students' low self-control on academic achievement via mastery goals, whereas teacher-student emotional support failed to moderate this link. Thus, both mediating and moderating effects exist in the association between self-control and adolescents' academic achievement.

Instant Messaging (IM) has become one of the most ubiquitous communication technologies worldwide. However, why IM has become popular and whether it is different for people with distinct interpersonal interaction characteristics remain unclear. This study attempts to explain the relations between adolescents' attachment styles and IM use by testing the mediating role of online interpersonal needs. Participants were 2245 adolescents from four Chinese junior high schools. Structural equation modeling results indicated that adolescents with higher attachment anxiety used IM more intensively, while those with higher attachment avoidance had lower levels of IM use intensity. Additionally, these links were mediated by online interpersonal needs that higher anxiously attached adolescents' more IM use was due to their more online interpersonal needs, and that higher avoidant adolescents' less IM use was accounted for by their less online interpersonal needs. These findings suggest that psychological needs offer an effective lens for understanding why IM has become popular and how it is different for people with distinct interpersonal interaction characteristics., Author(s): Caina Li [sup.1] , Jing Ma [sup.1] , Qingling Zhao [sup.1] , Hao Zhang [sup.1] [sup.2] , Ping Ren [sup.3] Author Affiliations: (1) grid.412498.2, 0000 0004 1759 8395, School [...]

The current two-wave longitudinal study sought to shed light on the well-established link between parental warm support and academic achievement by testing the potential mediating role of self-control and the moderating role of teacher emotional support among Chinese adolescents. 2569 Chinese students (45.22% girls; M.sub.age = 13.27, SD = 0.67 at baseline) completed self-reported measures at two time points, one year apart. The findings indicated that adolescents with higher parental warm support at baseline tended to have higher academic achievement one year later. Moreover, this link was mediated by self-control that parental warm support would heighten adolescents' self-control, and in turn increase their academic achievement one year later. Additionally, it was found that when teacher emotional support was higher, parental warmth support at baseline would heighten more academic achievement one year later through self-control. The findings illustrate the value of integrating parents and teachers' support in adolescent development, which helps them establish better personality traits as high self-control to improve academic achievement., Author(s): Maaza Saeed [sup.1] [sup.2] , Qingling Zhao [sup.1] [sup.2] , Bin Zhang [sup.1] [sup.2] , Caina Li [sup.1] [sup.2] Author Affiliations: (1) grid.412498.2, 0000 0004 1759 8395, School of [...]

Off-time pubertal timing has been linked to an increased risk of adolescent depressive symptoms, but the mechanisms underlying these associations are not well understood, particularly in a Chinese context. This three-wave longitudinal study investigated whether the relations between pubertal timing and depressive symptoms were through sadness rumination, and conditional on parental solicitation, for both Chinese girls and boys. Surveys were administered to adolescents and their parents across three measurement occasions, one year apart. Nine-hundred and fifty Chinese adolescents (56.63% boys; M.sub.age = 13.18, SD = 0.66 at baseline) reported their depressive symptoms and sadness rumination, and one of their parents (61.70% mothers) reported their children's pubertal timing and parental solicitation. Results indicated that early pubertal timing at baseline would increase girls' (but not boys') depressive symptoms two years later via elevated sadness rumination. Furthermore, it was found that when parental solicitation was higher, this indirect effect was no longer significant. These findings suggest that early maturation is a potential risk factor for adolescent girls' depressive symptoms, while high parental solicitation appears to buffer this pubertal risk through attenuating sadness rumination. Thus, early maturing girls would benefit from developing healthier cognitive strategies, parental initiative communications with them, or adequate sex education., Author(s): Caina Li [sup.1] [sup.2] , Qingling Zhao [sup.1] [sup.2] , Lijuan Zhang [sup.1] [sup.2] [sup.3] , Yunyun Zhang [sup.4] Author Affiliations: (1) grid.412498.2, 0000 0004 1759 8395, School of [...]

Aim: Non‐alcoholic fatty liver is the most common cause of chronic liver disease. GPR40 is a potential therapeutic target for energy metabolic disorders. GPR40 is a potential therapeutic target for energy metabolic disorders. SZZ15‐11 is a newly synthesized GPR40 agonist. In this study, we estimate the potency of SZZ15‐11 in fatty liver treatment. Methods: In vivo, diet‐induced obese (DIO) mice received SZZ15‐11 (50 mg/kg) and TAK875 (50 mg/kg) for 6 weeks. Blood glucose and lipid, hepatocyte lipid and liver morphology were analysed. In vitro, HepG2 cells and GPR40‐knockdown HepG2 cells induced with 0.3 mM oleic acid were treated with SZZ15‐11. Triglyceride and total cholesterol of cells were measured. At the same time, the AMPK pathway regulating triglycerides and cholesterol esters synthesis was investigated via western blot and quantitative polymerase chain reaction in both liver tissue and HepG2 cells. Results: SZZ15‐11 was found to not only attenuate hyperglycaemia and hyperlipidaemia but also ameliorate fatty liver disease in DIO mice. At the same time, SZZ15‐11 decreased triglyceride and total cholesterol content in HepG2 cells. Whether examined in the liver of DIO mice or in HepG2 cells, SZZ15‐11 upregulated AMPKα phosphorylation and then downregulated the expression of the cholesterogenic key enzyme 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase and inhibited acetyl‐CoA carboxylase activity. Furthermore, SZZ15‐11 promotes AMPK activity via [cAMP]i accumulation. Conclusion: This study confirmed that SZZ15‐11, a novel GPR40 agonist, improves hyperlipidaemia and fatty liver, partially via Gs signalling and the AMPK pathway in hepatocytes. [ABSTRACT FROM AUTHOR]

Reciprocal self‐disclosure has reportedly been associated with increased interpersonal trust. However, existing research mainly focuses on online disclosure between acquaintances and overlooks the types of reciprocal disclosure, especially in the initial interactions between strangers communicating online. This study aimed to investigate how three types of reciprocal self‐disclosure (turn‐taking reciprocity, extended reciprocity and non‐reciprocity) contribute to trust and the mechanism of positive interpersonal liking, and whether any effect was instant and stable or increased across two interactions during computer‐mediated communication (CMC). Participants were assigned to one of the three reciprocal disclosure conditions and engaged in online interactions. Self‐reported and behavioural results demonstrated higher levels of interpersonal trust and liking in the second interaction phase than in the first across all conditions. The turn‐taking reciprocity condition showed higher interpersonal trust than did the extended condition, and higher interpersonal liking than did the extended and non‐reciprocity conditions; this effect was apparent in both interactions. These findings help us understand the relationship between online self‐disclosure and interpersonal trust, suggesting that certain patterns of communication with strangers (e.g., turn‐taking reciprocity) may foster more positive social outcomes during CMC over time, while demonstrating the importance of immediacy in synchronous conversations. [ABSTRACT FROM AUTHOR]

The current three-wave longitudinal study investigated whether peer victimization would activate adolescents' rumination and rejection sensitivity, and therefore exacerbate subsequent loneliness. Surveys were administered to adolescents across three measurements, one year apart. Eight hundred and fifty-seven Chinese adolescents (56.62% males; Mage = 14.73, SD = 0.43) completed self-reported and peer-nominated measures of victimization, rumination, rejection sensitivity and loneliness. Results revealed that self-reported, but not peer-nominated victimization at baseline directly predicted adolescent loneliness one year later. Moreover, both rumination and rejection sensitivity exerted mediating effects on the relationship between self-reported victimization and loneliness. Additionally, this parallel mediation model was robust across gender. These findings suggest that self-perceived peer victimization would increase Chinese adolescents' loneliness since they employ rumination and rejection sensitivity to cope with peer victimization. [ABSTRACT FROM AUTHOR]

Voglibose is an α-glycosidase inhibitor that improves postprandial hyperglycemia and increases glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes. Recently, there has been increasing interest in the anti-inflammatory effects of voglibose on the intestine, but the underlying mechanism is not clear. This study evaluated the effects and mechanisms of voglibose on glycemic control and intestinal inflammation. Type 2 diabetic KKAy mice were treated with voglibose (1 mg/kg) by oral gavage once daily. After 8 weeks, glucose metabolism, levels of short-chain fatty acids (SCFAs), systematic inflammatory factors, intestinal integrity and inflammation were evaluated using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and Western blot analysis. Voglibose ameliorated glucose metabolism by enhancing basal- and glucose-dependent GLP-1 secretion. Several beneficial SCFAs, such as acetic acid and propionic acid, were increased by voglibose in the fecal sample. Additionally, voglibose notably decreased the proportion of pro-inflammatory macrophages and the expression of nuclear factor kappa B but increased the expression of tight junction proteins in the ileum, thus markedly improving intestinal inflammatory damage and reducing the systematic inflammatory factors. Ileal genomics and protein validation suggested that voglibose attenuated inositol-requiring protein 1α-X-box binding protein 1-mediated endoplasmic reticulum stress (ERS). Together, these results showed that voglibose enhanced the secretion of GLP-1, which contributed to the glycemic control in KKAy mice at least in part by regulating intestinal inflammation and the expression of ERS factors. [ABSTRACT FROM AUTHOR]

This three-wave longitudinal study aimed to investigate whether the relationship between self-control and academic achievement, through mastery goals, was conditional on the nature of the teacher-student relationships. A total of 852 junior school students in China completed questionnaires about self-control, mastery goals, and teacher-student relationships. Academic achievement was obtained from the school. The analyses of moderated mediation effects based on structural equation modeling showed that teacher-student emotional conflict increased the negative effect of students' low self-control on academic achievement via mastery goals, whereas teacher-student emotional support failed to moderate this link. Thus, both mediating and moderating effects exist in the association between self-control and adolescents' academic achievement. [ABSTRACT FROM AUTHOR]

Hyperglycemia, oxidative stress, and inflammation play key roles in the onset and development of diabetic complications such as diabetic nephropathy (DN). Diphenyl diselenide (DPDS) is a stable and simple organic selenium compound with anti-hyperglycemic, anti-inflammatory, and anti-oxidative activities. Nevertheless, in vitro, the role and molecular mechanism of DPDS on DN remains unknown. Therefore, we investigated the effects of DPDS on tert-butyl hydrogen peroxide (t-BHP)-induced oxidative stress and lipopolysaccharide (LPS)-induced inflammation in rat glomerular mesangial (HBZY-1) cells and explored the underlying mechanisms. DPDS attenuated t-BHP-induced cytotoxicity, concurrent with decreased intracellular ROS and MDA contents and increased SOD activity and GSH content. Moreover, DPDS augmented the protein and mRNA expression of Nrf2, HO-1, NQO1, and GCLC in t-BHP-stimulated HBZY-1 cells. In addition, DPDS suppressed LPS-induced elevations of intracellular content and mRNA expression of interleukin (IL)-6, IL-1β and TNF-α. Furthermore, LPS-induced NFκB activation and high phosphorylation of JNK and ERK1/2 were markedly suppressed by DPDS in HBZY-1 cells. In summary, these data demonstrated that DPDS improves t-BHP-induced oxidative stress by activating the Nrf2/Keap1 pathway, and also improves LPS-induced inflammation via inhibition of the NFκB/MAPK pathways in HBZY-1 cells, suggesting that DPDS has the potential to be developed as a candidate for the prevention and treatment of DN. [ABSTRACT FROM AUTHOR]

Although research has documented the adverse effect of peer victimization on academic achievement, little is known about the underlying mechanism. This three-wave longitudinal study attempts to examine whether school burnout would explain the influence of peer victimization on academic achievement and whether this undesirable effect would be conditional on parental warmth using a sample of 706 Chinese adolescents (54.77% boys; M age = 12.72 years, SD = 0.40 at baseline). Both self-reported and peer-nominated victimization, school burnout, and parental warmth were assessed at baseline, and school burnout was measured 1 year later. Their academic achievement was collected from school records at baseline and 2 years later. The results revealed that self-reported (rather than peer-nominated) victimization at baseline impaired students' academic achievement 2 years later through increasing their school burnout. Interestingly, higher parental warmth aggravated, rather than alleviated this indirect effect. These findings support the Reverse Stress-Buffering Model and the Ecological Systems Theory highlighting the importance of considering multiple interpersonal relationships simultaneously to heighten adolescent academic performance. [ABSTRACT FROM AUTHOR]

Background: Morus alba L. (Sangzhi) alkaloids (SZ-A), extracted from the Chinese herb Morus alba L. (mulberry twig), have been shown to ameliorate hyperglycemia in type 2 diabetes and have been approved for diabetes treatment in the clinic. However, their versatile pharmacologic effects and regulatory mechanisms are not yet completely understood. Purpose: This study explored the protective effects of SZ-A on islet β cells and the underlying mechanism. Methods: Type 2 diabetic KKAy mice were orally administered SZ-A (100 or 200 mg/kg, once daily) for 11 weeks, and oral glucose tolerance, insulin tolerance, intraperitoneal glucose tolerance and hyperglycemia clamp tests were carried out to evaluate the potency of SZ-A in vivo. The morphology and β-cell dedifferentiation marker of KKAy mouse islets were detected via immunofluorescence. The effect of SZ-A on glucose-stimulated insulin secretion was investigated in both the islet β-cell line MIN6 and mouse primary islets. Potential regulatory signals and pathways in insulin secretion were explored, and cell proliferation assays and apoptosis TUNEL staining were performed on SZ-A-treated MIN6 cells. Results: SZ-A alleviated hyperglycemia and glucose intolerance in type 2 diabetic KKAy mice and improved the function and morphology of diabetic islets. In both MIN6 cells and primary islets, SZ-A promoted insulin secretion. At a normal glucose level, SZ-A decreased AMPKα phosphorylation, and at high glucose, SZ-A augmented the cytosolic calcium concentration. Additionally, SZ-A downregulated the β-cell dedifferentiation marker ALDH1A3 and upregulated β-cell identifying genes, such as Ins1 , Ins2 , Nkx2.2 and Pax4 in KKAy mice islets. At the same time, SZ-A attenuated glucolipotoxicity-induced apoptosis in MIN6 cells, and inhibited Erk1/2 phosphorylation and caspase 3 activity. The major active fractions of SZ-A, namely DNJ, FAG and DAB, participated in the above regulatory effects. Conclusion: Our findings suggest that SZ-A promotes insulin secretion in islet β cells and ameliorates β-cell dysfunction and mass reduction under diabetic conditions both in vivo and in vitro , providing additional supportive evidence for the clinical application of SZ-A. [ABSTRACT FROM AUTHOR]

This longitudinal study examined the link between peer victimization and relational aggression by testing the mediating roles of sadness and anger rumination, with attention to gender differences, among Chinese adolescents. Survey measures were administrated to 2,152 junior middle school students at two time points, one year apart. The results found that self-reported peer victimization (but not peer-nominated victimization) positively predicted relational aggression one year later, and this link was completely mediated by sadness and anger rumination. Specifically, perceived peer victimization exerted a positive influence on both sadness and anger rumination, thereby increasing adolescents' tendency to exhibit relational aggression one year later. Furthermore, victimized boys' elevated relational aggression was predominantly accounted for by their high sadness rumination, whereas victimized girls' elevated relational aggression was mainly due to their great anger rumination. Such a gender-difference suggests that interventions to reduce adolescents' externalizing problems may be most effective when tailored to each gender specifically. [ABSTRACT FROM AUTHOR]

The effects of the combination of bis (α‐furancarboxylato) oxovanadium (IV) (BFOV) and metformin (Met) on hepatic steatosis were investigated in high‐fat diet‐induced obese C57BL/6J mice (HFC57 mice) for 6 weeks. Oral glucose tolerance test was performed to evaluate glucose metabolism. Moreover, blood and hepatic biochemical and histological indices were detected. Besides, Affymetrix‐GeneChip analysis and Western blot of the liver were performed. Comparing to the monotherapy group, BFOV + Met showed more effective improvement in glucose metabolism, which decreased the fasting blood glucose, insulin levels and improved insulin sensitivity in HFC57 mice. BFOV + Met significantly decreased serum ALT and AST activities and reduced hepatic triglyceride content and iNOS activities, accompanied by ameliorating intrahepatic fat accumulation and hepatocellular vacuolation. Enhanced hepatic insulin signalling transduction and attenuated inflammation pathway were identified as the major pathways in the BFOV + Met group. BFOV + Met significantly down‐regulated the protein expression levels of MMPs, NF‐κB, iNOS and up‐regulated phosphorylation of AKT and AMPK levels. We concluded that a combination of BFOV and metformin ameliorates hepatic steatosis in HFC57 mice via alleviating hepatic inflammation and enhancing insulin signalling pathway, suggesting that the combination of BFOV and metformin is a potential treatment for hepatic steatosis. [ABSTRACT FROM AUTHOR]

The cereal formula powder, Zhengda Jingshan (ZDJS), comprises dietary fiber, multivitamins, fine protein, and various cereal ingredients. The present study evaluated the effects of ZDJS on glucose metabolism and explored the corresponding mechanisms in terms of modulating gut microbiota and the fecal metabolome. Type 2 diabetic db/db mice were given ZDJS (1 g/kg) orally twice daily for 55 days, after which glucose metabolism, inflammation, gut microbiota, and fecal metabolomics were assayed. Repeated administration of ZDJS was associated with a trend toward decreasing fasting blood glucose and a 0.12% decrease in hemoglobin A1c (HbA1c), as well as statistically significant increases in the insulin sensitivity index and decreases in serum levels of tumor necrosis factor (TNF‐α) and ileum expression of mucin‐2. ZDJS also ameliorated the compensatory enlargement of islets and decreased the ratio of the α‐cell area to total islet area; however, this amelioration of impaired oral glucose tolerance became less pronounced as treatment continued. In addition, ZDJS remarkably decreased the abundance of phylum Proteobacteria and the phylum ratio of Firmicutes to Bacteroidetes, as well as altered the fecal metabolic profile. Taken together, our findings demonstrate that ZDJS improved glucose metabolism and reduced inflammation in type 2 diabetic db/db mice, which may be associated with a reshaping of the gut microbiome and fecal metabolome in db/db mice. Thus, our study suggests that ZDJS may represent a complementary therapy for patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: To evaluate a novel tetrahydroisoquinoline derivative YR4‐42 as a selective peroxisome proliferator‐activated receptor γ (PPARγ) modulator (SPPARM) and explore its anti‐diabetic effects in vitro and in vivo. Materials and methods: Using two standard full PPARγ agonists rosiglitazone and pioglitazone as controls, the PPARγ binding affinity and transactivation action of YR4‐42 were evaluated using biochemical and cell‐based reporter gene assays. The capacity of YR4‐42 to recruit coactivators of PPARγ was also assessed. The effects of YR4‐42 on adipogenesis and glucose consumption and PPARγ Ser273 phosphorylation were investigated in 3T3‐L1 adipocytes. The effects of YR4‐42 and pioglitazone, serving as positive control, on glucose and lipids metabolism were investigated in high‐fat diet‐induced obese (DIO) C57BL/6J mice. The expression of PPARγ target genes involved in glucose and lipid metabolism was also assessed in vitro and in vivo. Results: In vitro biochemical and cell‐based functional assays showed that YR4‐42 has much weaker binding affinity, transactivation, and recruitment to PPARγ of the coactivators thyroid hormone receptor‐associated protein complex 220 kDa component (TRAP220) and PPARγ coactivator 1‐α (PGC1α) compared to full agonists. In 3 T3‐L1 adipocytes, YR4‐42 significantly improved glucose consumption without a lipogenesis effect, while blocking tumour necrosis factor α‐mediated phosphorylation of PPARγ at Ser273, thereby upregulating the expression of the PPARγ Ser273 phosphorylation‐dependent genes. Furthermore, in DIO mice, oral administration of YR4‐42 ameliorated the hyperglycaemia, with a similar insulin sensitization effect to that of pioglitazone. Importantly, YR4‐42 also improved hyperlipidaemia‐associated hepatic steatosis without weight gain, which avoids a major side effect of pioglitazone. Thus, YR4‐42 appeared to selectively modulate PPARγ responses. This finding was supported by the gene expression analysis, which showed that YR4‐42 selectively targets PPARγ‐regulated genes mapped to glucose and lipid metabolism in DIO mice. Conclusions: We conclude that YR4‐42 is a novel anti‐diabetic drug candidate with significant advantages compared to standard PPARγ agonists. YR4‐42 should be further investigated in preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

Research suggests people try to protect their social self-esteem from threats from the ingroup or the outgroup. However, how members react to a threat to social self-esteem from a third party remains unclear. Three studies were conducted to examine the influence of a threat to social self-esteem from an authoritative third party on ingroup favoritism. We explored the effect of negative (versus positive) evaluation from the testing system on explicit and implicit ingroup favoritism in Study 1 and Study 2 respectively. We compared the effect of negative evaluation posed by the testing system or the competitive outgroup on ingroup favoritism in Study 3. Results suggested that individuals experiencing a threat to social self-esteem from an authoritative third party manifested less ingroup favoritism than those experiencing no threat or outgroup threat. The theoretical implications of this research on social identity theory and the practical implications of reducing intergroup bias are discussed. [ABSTRACT FROM AUTHOR]

Aims Glucagon like-peptide-1 (GLP-1)-based drugs have been proposed as mono- or combined therapy for type 2 diabetes mellitus. Thus we characterized a novel antibody fusion protein engineered by linking the human GLP-1 derivative to a humanized GLP-1 receptor (GLP-1R) antibody via a peptide linker. Materials and methods Glutazumab was characterized by receptor binding and reporter activation assays, and its specificity was investigated with the aid of the cognate receptor antagonist exendin (9-39) and antibody Ab1. Pharmacokinetics was evaluated in Sprague-Dawley (SD) rats and cynomolgus monkeys, and pharmacodynamics was assessed in normal ICR and spontaneous type 2 diabetic KKAy mice. Hypoglycemic effects were evaluated after acute administration and glucose metabolism and β-cell function were assessed with repeated administrations. Dulaglutide was a positive control in all experiments. Results Glutazumab significantly bound and activated GLP-1R, but the receptor antagonist exendin (9-39) did not inhibit the activation except when combined with Ab1. Single injection of glutazumab reduced the blood glucose in ICR mice and KKAy mice, and the half-lives in SD rats and cynomolgus monkeys were 18 h and 33.6 h. Repeated injections of glutazumab controlled glycemic fluctuations and improved β-cell function in KKAy mice. Conclusions As a novel GLP-1R agonist, glutazumab may be a potential treatment for T2DM. [ABSTRACT FROM AUTHOR]

Al2O3-SiO2composite nanofibers were fabricated by calcining the precursor fibers obtained through sol–gel processing and electrospinning technique. Thermogravity-differential scanning calorimeter, powder X-ray diffraction, X-ray fluorescence analysis, scanning electron microscopy, transmission electron microscopy, and thermal conductivity instrument were employed to characterize the fibers. Upon calcining the precursor fibers at 1300°C, continuous Al2O3-SiO2composite nanofibers with diameter of about 300 nm can be obtained. The calcined fibers had low thermal conductivity, which might favor their application in high-temperature insulation areas. [ABSTRACT FROM PUBLISHER]

Refined-JQ (JQ-R) is a mixture of refined extracts from Coptis chinensis (Ranunculaceae), Astragalus membranaceus (Leguminosae) and Lonicera japonica (Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KK Ay mice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KK Ay mice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B (NF- κ B p65), inhibitor of NF- κ B (I κ B α ), c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KK Ay mice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Prior research has documented a relationship between narcissism and aggression but has focused only on dispositional narcissism without considering situational factors that may increase narcissism temporarily. This study explored the possibility that an increase in state narcissism would foster aggressive responding by increasing anger and hostile attributional bias following unexpected provocation among 162 college students from China. We created a guided-imagination manipulation to heighten narcissism and investigated its effects on anger, aroused hostile attribution bias, and aggressive responses following a provocation with a 2 (narcissism/neutral manipulation) × 2 (unexpected provocation/positive evaluation condition) between-subjects design. We found that the manipulation did increase self-reported state narcissism. The increase in state narcissism in turn heightened aggression, and this relation was mediated by increased anger. Regardless of the level of state narcissism, individuals were more aggressive after being provoked and this effect of provocation was mediated by hostile attributional bias. The findings indicate that narcissism can be temporarily heightened in a nonclinical sample of individuals, and that the effect of state narcissism on aggression is mediated by anger. Differences between state and trait narcissism and possible influences of culture are discussed. Aggr. Behav. 42:333-345, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Dipeptidyl peptidase 4 (DPP4) is recognised as an attractive anti-diabetic drug target, and several DPP4 inhibitors are already on the market. As members of the same gene family, dipeptidyl peptidase 8 (DPP8) and dipeptidyl peptidase 9 (DPP9) share high sequence and structural homology as well as functional activity with DPP4. However, the inhibition of their activities was reported to cause severe toxicities. Thus, the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic therapy. To achieve this goal, we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta cells. In this method, we used purified recombinant 120kDa DPP8 or DPP9 protein from the Rosetta expression system. The optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30ng/mL and 20ng/mL, respectively, and the corresponding concentrations of their substrates were both 0.2mmol/L. This method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates, which would provide valuable guidance in the development of safe DPP4 inhibitors. [Copyright &y& Elsevier]

Abstract: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that decreases postprandial glycemic excursions by enhancing insulin secretion but with short half-life due to rapid inactivation by enzymatic N-terminal truncation. Therefore, efforts are being made to improve the stability of GLP-1 via modifying its structure or inhibiting dipeptidyl-peptidase IV (DPP IV), which is responsible for its degradation. Here we report a novel GLP-1 analog BPI3006 with –NHCO– of Ala8 replaced by –CH(CF3)NH– and features of its metabolic stability, GLP-1 receptor trans-activation and in vivo biological activity. BPI3006 is highly resistant to DPP IV-mediated degradation with 91.1% of parental peptide left after 24h exposure to the enzyme. BPI3006 also effectively activates its target gene promoter through GLP-1 receptor activation by measuring the transiently transfected reporter gene green fluorescence protein (GFP) expression in NIT-1 cells. Furthermore, BPI3006 could well restrain the glycemia variation in fasted normal ICR mice after a single administration followed by an oral glucose loading. In spontaneous type 2 diabetic KKAy mice, BPI3006 injected twice daily could significantly improve the oral glucose tolerance and hyperinsulinemia, as well as ameliorate the food and water consumption. In conclusion, BPI3006 has enhanced resistance to DPP IV leading to improved stability, and shows excellent in vivo biological activity. Thus it may be a new candidate for T2DM treatment and its novel modification may provide valuable guidance for the future development of long-acting GLP-1 analogs. [ABSTRACT FROM AUTHOR]

The novel Traditional Chinese Medicine Ramulus Mori (Sangzhi) alkaloid tablets (SZ-A) are approved by The China National Medical Products Administration for the treatment of type 2 diabetes mellitus (T2DM). However, the extensive pharmacological characteristics and the underlying mechanism are unknown. This study investigated the mechanisms by which SZ-A ameliorates glucose metabolism in KKAy mice, an animal model of T2DM. Diabetic KKAy mice were treated intragastrically with SZ-A once daily for 8 weeks, after which glucose levels, lipid metabolism, gut microbiome, systemic inflammatory factors, luminal concentrations of short-chain fatty acids (fecal samples), and ileal proteomic changes were evaluated. The ileum tissues were collected, and the effects of SZ-A on pathological inflammatory damage were evaluated by hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. The mRNA and protein expression levels of various inflammatory markers, including monocyte chemoattractant protein-1 and phosphorylated nuclear factor kappa B p65, were detected in the ileum tissues. SZ-A improved glucose metabolism with enhanced insulin response and elevated glucagon-like peptide 1 (GLP-1) nearly 2.7-fold during the glucose tolerance test in diabetic KKAy mice. Gut microbiota analysis demonstrated that SZ-A administration elevated the abundance of Bacteroidaceae and Verrucomicrobia , reduced the levels of Rikenellaceae and Desulfovibrionaceae; and increased the concentrations of fecal acetic and propionic acids compared to the diabetic model group. Additionally, SZ-A markedly improved ileal inflammatory injury and pro-inflammatory macrophage infiltration and improved intestinal mucosal barrier function in diabetic KKAy mice. SZ-A also attenuated the levels of circulating endotoxin, pro-inflammatory cytokines, and chemokines in the mice sera. Collectively, SZ-A ameliorated the overall metabolic profile including glucose and lipid metabolism in KKAy mice, which may be associated with an improvement in GLP-1 and insulin secretion, at least in part by modulating the gut microbiome and relieving the degree of ileal and systemic inflammation. [ABSTRACT FROM AUTHOR]

Oxidative stress and inflammation are implicated in the occurrence and progression of diabetic nephropathy (DN). Diphenyl diselenide (DPDS) is a stable and simple diaryl diselenide with anti-hyperglycemic, anti-inflammatory, and antioxidant activities. However, the effects of DPDS on DN are still unclear to date. Herein, we aimed to explore whether DPDS could improve renal dysfunction in streptozotocin (STZ)-induced diabetic rats and its underlying mechanisms. STZ-induced DN rats were administered with DPDS (5 or 15 mg/kg) or metformin (200 mg/kg) once daily by intragastric gavage for 12 weeks. DPDS supplementation significantly improved hyperglycemia, glucose intolerance, dyslipidemia, and the renal pathological abnormalities, concurrent with significantly reduced serum levels of creatinine, urea nitrogen, urine volume, and urinary levels of micro-albumin, β2-microglobulin and N-acetyl-glucosaminidase activities. Moreover, DPDS effectively promoted the activities of antioxidant enzymes, and reduced the levels of MDA and pro-inflammatory factors in serum and the kidney. Furthermore, DPDS supplementation activated the renal Nrf2/Keap1 signaling pathway, but attenuated the high phosphorylation levels of NFκB, JNK, p38 and ERK1/2. Altogether, the current study indicated for the first time that DPDS ameliorated STZ-induced renal dysfunction in rats, and its mechanism of action may be attributable to suppressing oxidative stress via activating the renal Nrf2/Keap1 signaling pathway and mitigating inflammation by suppressing the renal NFκB/MAPK signaling pathways, suggesting a potential therapeutic approach for DN. [Display omitted] • Diphenyl diselenide (DPDS) ameliorated STZ-induced diabetic nephropathy in rats. • DPDS ameliorated systemic and renal oxidative stress in diabetic rats. • DPDS ameliorated systemic and renal inflammation in diabetic rats. • DPDS activated the renal Nrf2/Keap1 signaling pathway in diabetic rats. • DPDS suppressed the renal NFκB and MAPK signaling pathways in diabetic rats. [ABSTRACT FROM AUTHOR]

Berberine (BBR) has the beneficial effects of anti-inflammation, anti-bacteria, and anti-diabetes. The clinical application of BBR has been hindered by its poor gastrointestinal absorption. Stachyose (Sta), a prebiotic agent, improves the composition of gut microbiota and benefits for diabetes. We therefore investigated whether Sta improves the anti-diabetic actions of BBR using KKAy mice. Here, we find that the combination of BBR and Sta is more effective than BBR alone in blood glucose control, improvement of insulin resistance and islet functions, inflammatory mediators decrease, and maintenance of intestinal barrier integrity. Gut microbiota analysis demonstrates that both BBR and combined administration enhance the abundance of Bacteroidaceae and Akkermansiaceae and decrease Lachnospiraceae levels, whereas Akkermansiaceae elevation due to the administration of BBR with Sta is more significant than BBR alone. Interestingly, the proportion of Lactobacillaceae increases with combination treatment, but is diminished by BBR. Additionally, BBR with Sta significantly reduces the concentrations of fecal short-chain fatty acids compared to BBR. Collectively, these results indicate that the combination of BBR and Sta imparts better effects on the maintenance of glycemia and intestinal homeostasis than BBR alone by modulating gut microbiota and short-chain fatty acids, thereby providing a novel approach for the treatment of type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Family violence as an inducing factor of depressive symptoms has been confirmed in previous studies. However, the mechanisms underlying this association are not well understood, particularly in Chinese adolescents. Guided by the social-ecological diathesis-stress model, this three-wave longitudinal study aimed to examine the effects of an individual's cognitive vulnerabilities (rejection-sensitivity anxiety and negative cognitive error) and positive societal contexts (peer support) on the link between family violence and depressive symptoms in Chinese society. A total of 859 Chinese adolescents (44.35 % female; M age = 12.73, SD = 0.43 at baseline) completed self-reporting surveys that assessed variables associated with study and peer-nominated peer support. The results showed that family violence increased the incidence of depressive symptoms in adolescents after two years, resulting in rejection-sensitivity anxiety and negative cognitive error. Surprisingly, higher self-reported peer support, although not peer-nominated support, exacerbated rather than mitigated this indirect effect, supporting the reverse stress-buffering model and extending the healthy context paradox. Most of the measures were based on participants' self-reports. These results emphasize the importance of individual cognition and societal contexts in adolescents with traumatic experiences and provide empirical evidence for the intervention and clinical treatment of depressive symptoms. • The experience of family violence at baseline significantly predicted adolescent depressive symptoms two years later. • Family violence increased adolescent depressive symptoms 2 years later via cognitive vulnerabilities. • Higher self-reported peer support exacerbated this indirect effect between family violence and depressive symptoms. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients. Oxidative stress (OS) plays a key role in the pathogenesis of DPN; thus, antioxidant therapy is considered a promising strategy for treating DPN. Diphenyl diselenide (DPDs) is an organic selenium compound with antioxidant pharmacological activities. This study aimed to evaluate its preventive and therapeutic effects on DPN in rats with streptozotocin (STZ)-induced diabetes and explore the underlying mechanisms. In vitro, RSC96 cells were exposed to high glucose (100 mM) and then treated with different concentrations of DPDs (1, 10, 25 and 50 μM). Notably, DPDs markedly suppressed high glucose-induced cytotoxicity and oxidative stress in Schwann cells by decreasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Furthermore, the DPDs treatment effectively activated Nrf2 signaling and inhibited Keap1 expression. An in vivo DPN model was established in Sprague-Dawley (SD) rats injected with STZ (60 mg·kg−1, ip) and orally administered either different doses of DPDs (5 and 15 mg· kg−1· d−1) for 12 weeks or alpha lipoic acid (ALA, 100 mg kg−1·d−1) as a positive control. The administration of DPDs significantly increased the motor nerve conduction velocity (MNCV), improved thermal and mechanical hyperalgesia and the sciatic nerve morphology, and ameliorated oxidative stress in the serum and the sciatic nerve of rats with DPN. Mechanistically, DPDs reduced the level of Keap1 and stimulated Nrf2 signaling in the sciatic nerve. Taken together, the results of this study indicate that DPDs ameliorates experimental DPN as an antioxidant by activating the Nrf2/Keap1 signaling pathway. DPDs may represent a new alternative treatment for DPN. [ABSTRACT FROM AUTHOR]

Abstract Recently, SIRT5 was reported to be a predominant desuccinylase and demalonylase in mitochondria. Ablation of SIRT5 enhances the systemic succinylation and malonylation of mitochondrial proteins, including various metabolic enzymes; however, its function in pancreatic β cells has not yet been clarified. In this study, we evaluated the effects of SIRT5 overexpression on glucolipotoxicity-induced apoptosis in β cell lines. Full-length SIRT5, which preferentially targeted to mitochondria and partially to the nucleus and cytoplasm, was overexpressed in NIT-1 cells. Chronic exposure to excess palmitate and glucose (High-PA-G) induced apoptosis and suppressed glucose-stimulated insulin secretion in β cells. SIRT5 overexpression significantly alleviated apoptosis under the High-PA-G condition, accompanied by suppressed Caspase 3 activity and reduced malondialdehyde levels. SIRT5 overexpression also improved β cell secretory capacity in response to glucose under the High-PA-G condition, suggesting its protective role in β cell function. Furthermore, SIRT5 overexpression reversed the decreasing trend of anti-apoptotic factors BCL-2 and BCL-XL expression under High-PA-G condition. Further regulation mechanisms between SIRT5 and these anti-apoptotic factors remains to be explored in future studies. Our data reveal that SIRT5 is a potentially protective factor for pancreatic β cells against glucolipotoxicity-induced apoptosis and cell dysfunction. Highlights • SIRT5 expression significantly diminished in the pancreas of T2DM animals. • SIRT5 reduced apoptotic cell mass and retained glucose-stimulated insulin secretion in β cell lines upon glucolipotoxicity. • SIRT5 plays an essential role in maintaining the β cell mass and function under glucolipotoxicity condition. [ABSTRACT FROM AUTHOR]