Identification of SNPs and INDELS associated with duck egg quality traits through a genome-wide association analysis.

Egg quality traits are economically important in the poultry industry. To explore the genetic architecture and identify potential candidate genes, a genome-wide association study (GWAS) was performed for 13 egg quality traits using data from whole-genome sequencing of 299 Longyan Shan-ma female ducks, including 12 quantitative traits and one qualitative trait, eggshell color (ESC; white, light green, green). From estimation of pedigree genetic parameters, heritability (h2) ranged from 0.022 to 0.996 for the 12 quantitative traits, with the highest h2 (0.996) for eggshell color a* value (ESCA) and the lowest h2 (0.022) for egg yolk percentage relative to EW. A total of 8,874 single nucleotide polymorphism (SNP)-based significant associations (1.0 × 10-6) and 247 insertion-deletion (indel)-based significant associations (1.00 × 10-5) were identified, including 5,980 SNPs and 159 indel markers. From 5,924 SNPs and 143 indels associated with ESC traits, 181 potential candidate genes were identified, and most significant SNPs and indels (P < 1.0 × 10-20) were located at 1.86 Mb (44.29-46.15 Mb) on chromosome 4. The top SNP (chr4:45325309:C>A; P = 7.97 × 10-43) and the top indel (chr4:45299595:delTTCCACTCCAC; P = 4.20 × 10-36) for the ESC a* value were within two known ESC candidate genes; ATP-binding cassette subfamily G member 2 (ABCG2) and protein kinase cGMP-dependent 2 (PRKG2). Of 56 SNPs and 16 indels associated with other egg quality traits, 46 potential candidate genes were identified including synapse differentiation-inducing 1-like (SYNDIG1L) for EW, and core histone macro-H2A.1 (LOC101795967) and neurogenin 1 (NEUROG1) for egg shape index; and four genes including collagen type VI alpha 3 chain (COL6A3), lysine demethylase 7A (KDM7A), LOC101802169, and sperm-associated antigen 16 (SPAG16) for egg yolk weight and the percentage of yolk to total egg weight. Of the 46 genes, the molecular functions of 22 are related to protein binding, indicating important roles in the formation of egg quality traits. Our findings provide new insight into the genetic basis of egg quality traits in ducks.

Piceatannol Protects Sperm from Cryopreservation Damage by Modulating the Keap1-Nrf2/ARE Signaling Pathway.

The purpose of this study was to explore the mechanism of action of Piceatannol (PIC) in attenuating oxidative damage to sperm during cryopreservation. Semen samples were collected and homogenized into six equal parts for freeze-thawing experiments. Four different concentrations of PIC were utilized as cryoprotectants during the freeze-thawing process, maintaing a semen to PIC ratio of 1:1, while sperm motility after freezing and thawing was analyzed using computer-assisted sperm analysis (CASA). Sperm plasma membrane integrity was assessed via the hypo-osmotic swelling (HOS) test. The levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, long with the ability to scavenge sperm malondialdehyde (MDA), were examined in sperm following the addition of PIC. Quantitative real-time PCR (qRT-PCR) was performed to detect the expression levels of Keap1, Nrf2, GCLC, GCLM, and HMOX1 in sperm. The mechanism by which PIC protects sperm during cryopreservation from oxidative stress damage was further verified. Treatment with PIC at a dose of 5.0 µmol/L significantly improved both sperm motility and viability while effectively reducing ROS levels in frozen sperm. Additionally, the integrity of the sperm plasma membrane was significantly enhanced. Furthermore, the expression level of Keap1 was significantly reduced, whereas the expression levels of GCLC, GCLM, HMOX1, and Nrf2 were significantly increased (p < 0.05) after the addition of PIC. Notably, a significant attenuation of sperm motility and viability was observed in this treatment group when PIC treatment was accompanied by the addition of an Nrf2 inhibitor, resulting in a significant elevation of ROS levels. The finding that PIC modulates ROS in frozen sperm via the Keap1-Nrf2/ARE pathway thereby enhancing sperm viability levels after freezing and thawing provides a novel approach to optimize semen cryopreservation.

Lateral habenula IL-10 controls GABAA receptor trafficking and modulates depression susceptibility after maternal separation.

Maternal separation (MS), a form of early life adversity, increases the risk of psychiatric disorders in adulthood by intricately linking cytokines and mood-regulating brain circuits. The Lateral Habenula (LHb) encodes aversive experiences, contributes to negative moods, and is pivotal in depression development. However, the precise impact of MS on LHb cytokine signaling and synaptic plasticity remains unclear. We reported that adolescent MS offspring mice displayed susceptibility to depression behavioral phylotypes, with neuronal hyperactivity and an imbalance in pro-inflammatory and anti-inflammatory cytokines in the LHb. Moreover, the decreased IL-10 level negatively correlated with depressive-like behaviors in susceptible mice. Functionally, LHb IL-10 overexpression restored decreased levels of PI3K, phosphorylated AKT (pAKT), gephyrin, and membrane GABAA receptor proteins while reducing abnormally elevated GSK3ß and Fos expression, rescuing the MS-induced depression. Conversely, LHb neuronal IL-10 receptor knockdown in naive mice increased Fos expression and elicited depression-like symptoms, potentially through impaired membrane GABAA receptor trafficking by suppressing the PI3K/pAKT/gephyrin cascades. Hence, this work establishes a mechanism by which MS promotes susceptibility to adolescent depression by impeding the critical role of IL-10 signaling on neuronal GABAA receptor function.

The effect of justice sensitivity on malevolent creativity: the mediating role of anger and the moderating role of emotion regulation strategies.

BACKGROUND: the AMORAL model emphasizes the close connection of individuals' belief system and malevolent creativity. Belief in a just world theory (BJW) states that people have a basic need to believe that the world they live in is just, and everyone gets what they deserve. Therefore, justice matters to all people. Justice sensitivity, as one of individual trait, has been found associated with negative goals. However, relevant studies have not tested whether justice sensitivity can affect malevolent creativity and its psychological mechanisms. Additionally, researchers have found that both anger and emotion regulation linked with justice sensitivity and malevolent creativity, but their contribution to the relationship between justice sensitivity and malevolent creativity remained unclear. The current study aims to explore the influence of justice sensitivity on malevolent creativity, the mediating effect of trait anger/state anger on the relationship between justice sensitivity and malevolent creativity, and the moderating effect of emotion regulation on this mediating effect. METHODS: A moderated mediating model was constructed to test the relationship between justice sensitivity and malevolent creativity. A sample of 395 Chinese college students were enrolled to complete the questionnaire survey. RESULTS: Justice sensitivity positively correlated with malevolent creativity, both trait anger and state anger partly mediated the connection between justice sensitivity and malevolent creativity. Moreover, emotion regulation moderated the indirect effect of the mediation model. The indirect effect of justice sensitivity on malevolent creativity through trait anger/state anger increased as the level of emotion regulation increased. The results indicated that justice sensitivity can affect malevolent creativity directly and indirectly through the anger. The level of emotion regulation differentiated the indirect paths of justice sensitivity on malevolent creativity. CONCLUSIONS: Justice sensitivity and malevolent creativity was mediated by trait anger/state anger. The higher sensitivity to justice, the higher level of trait anger/state anger, which in turn boosted the tendency of malevolent creativity. This indirect connection was moderated by emotion regulation, individuals with high emotion regulation are better able to buffer anger from justice sensitivity.

Association between RMTg Neuropeptide Genes and Negative Effect during Alcohol Withdrawal in Mice.

Alcohol use disorders (AUDs) frequently co-occur with negative mood disorders, such as anxiety and depression, exacerbating relapse through dopaminergic dysfunction. Stress-related neuropeptides play a crucial role in AUD pathophysiology by modulating dopamine (DA) function. The rostromedial tegmental nucleus (RMTg), which inhibits midbrain dopamine neurons and signals aversion, has been shown to increase ethanol consumption and negative emotional states during abstinence. Despite some stress-related neuropeptides acting through the RMTg to affect addiction behaviors, their specific roles in alcohol-induced contexts remain underexplored. This study utilized an intermittent voluntary drinking model in mice to induce negative effect behavior 24 h into ethanol (EtOH) abstinence (post-EtOH). It examined changes in pro-stress (Pnoc, Oxt, Npy) and anti-stress (Crf, Pomc, Avp, Orx, Pdyn) neuropeptide-coding genes and analyzed their correlations with aversive behaviors. We observed that adult male C57BL/6J mice displayed evident anxiety, anhedonia, and depression-like symptoms at 24 h post-EtOH. The laser-capture microdissection technique, coupled with or without retrograde tracing, was used to harvest total ventral tegmental area (VTA)-projecting neurons or the intact RMTg area. The findings revealed that post-EtOH consistently reduced Pnoc and Orx levels while elevating Crf levels in these neuronal populations. Notably, RMTg Pnoc and Npy levels counteracted ethanol consumption and depression severity, while Crf levels were indicative of the mice's anxiety levels. Together, these results underscore the potential role of stress-related neuropeptides in the RMTg in regulating the negative emotions related to AUDs, offering novel insights for future research.

The mediating effects of dysfunctional attitudes and moderating effect of sex between stressful life events and depressive symptoms among Chinese college students.

Stressful life events (SLEs) closely correlates with depressive symptoms. Although vulnerability-stress model suggests SLEs interacted with dysfunctional attitudes (DA) to predict depression, the mediation role of DA is poorly understood. Therefore, this study intended to investigate the mediating role of DA and the moderating role of sex between SLEs and self-reported depression. A cross-sectional survey was conducted with a sample of 7769 Chinese college students. Participants were assessed in terms of self-reported SLEs, DA and depression variables. Results showed that there were significant sex differences in both SLE and DA. DA mediated the association between SLE and self-reported depression. The moderated mediation model analysis showed that the interaction of SLEs and sex significantly predicted DA in mediator variable model and self-reported depression in dependent variable model. Results indicated that DA partially mediated the association between SLEs and self-reported depression, and sex moderates the association between SLEs and both DA and self-reported depression, which females have bigger changes of DA and depressive symptoms across low and high levels of SLEs than males.

Childhood Maltreatment and Creativity among Chinese College Students: A Serial Mediation Model.

Creativity plays a very crucial impact on our cultural life and has also been important to the improvement of human civilization. Numerous studies have indicated that family circumstance plays an important role in the development of individual creativity. However, little is known about the mediating mechanisms underlying the association between childhood maltreatment and creativity. This study intended to explore the serial multiple mediation model in which undergraduates' cognitive flexibility and self-efficacy were proposed to mediate the potential influence of childhood maltreatment on their creativity. Participants were 1069 undergraduates (573 males and 496 females, mean age was 20.57 ± 1.24 years ranging from 17 to 24) from a university in Shandong Province, China. Participants were required to complete an internet survey including the Short Form of Childhood Trauma Questionnaire (CTQ-SF), General Self-Efficacy Scale (GSES), Cognitive Flexibility Inventory (CFI), and Williams Creativity Aptitude Test (WCAT). Serial multiple mediation analysis and the bootstrap method were used to investigate the mediation effects of cognitive flexibility and self-efficacy. The results showed that childhood maltreatment indirectly influenced undergraduates' creativity through three indirect paths: childhood maltreatment→cognitive flexibility→creativity, childhood maltreatment→self-efficacy→creativity, and childhood maltreatment→cognitive flexibility→self-efficacy→creativity. The ratios of the total indirect effects and branch-indirect effects to the total effects were 92.73%, 34.61%, 35.68%, and 22.44%, respectively. These results indicated that cognitive flexibility and self-efficacy could completely mediate the potential impact of childhood maltreatment on individuals creativity.

LPA1 receptors in the lateral habenula regulate negative affective states associated with alcohol withdrawal.

The role of lysophosphatidic acid (LPA) signaling in psychiatric disorders and drug abuse is significant. LPA receptors are widely expressed in the central nervous system, including the lateral habenula (LHb). Recent studies suggest that LHb is involved in a negative emotional state during alcohol withdrawal, which can lead to relapse. The current study examines the role of LHb LPA signaling in the negative affective state associated with alcohol withdrawal. Adult male Long-Evans rats were trained to consume either alcohol or water for eight weeks. At 48 h of withdrawal, alcohol-drinking rats showed anxiety- and depression-like symptoms, along with a significant increase in LPA signaling and related neuronal activation molecules, including autotaxin (ATX, Enpp2), LPA receptor 1/3 (LPA1/3), ßCaMKII, and c-Fos. However, there was a decrease in lipid phosphate phosphatase-related protein type 4 (LPPR4) in the LHb. Intra-LHb infusion of the LPA1/3 receptor antagonist ki-16425 or PKC-γ inhibitor Go-6983 reduced the abnormal behaviors and elevated relapse-like ethanol drinking. It also normalized high LPA1/3 receptors and enhanced AMPA GluA1 phosphorylation in Ser831 and GluA1/GluA2 ratio. Conversely, selective activation of LPA1/3 receptors by intra-LHb infusion of 18:1 LPA induced negative affective states and upregulated ßCaMKII-AMPA receptor phosphorylation in Naive rats, which were reversed by pretreatment with intra-LHb Go-6983. Our findings suggest that disturbances in LPA signaling contribute to adverse affective disorders during alcohol withdrawal, likely through PKC-γ/ßCaMKII-linked glutamate signaling. Targeting LPA may therefore be beneficial for individuals suffering from alcohol use disorders.

Rostromedial tegmental nucleus nociceptin/orphanin FQ (N/OFQ) signaling regulates anxiety- and depression-like behaviors in alcohol withdrawn rats.

Recent studies indicate that stimulation of the rostromedial tegmental nucleus (RMTg) can drive a negative affective state and that nociceptin/orphanin FQ (N/OFQ) may play a role in affective disorders and drug addiction. The N/OFQ precursor prepronociceptin encoding genes Pnoc are situated in RMTg neurons. To determine whether N/OFQ signaling contributes to the changes in both behavior phenotypes and RMTg activity of alcohol withdrawn (Post-EtOH) rats, we trained adult male Long-Evans rats, randomly assigned into the ethanol and Naïve groups to consume either 20% ethanol or water-only under an intermittent-access procedure. Using the fluorescence in situ hybridization technique combined with retrograde tracing, we show that the ventral tegmental area projecting RMTg neurons express Pnoc and nociceptin opioid peptide (NOP) receptors encoding gene Oprl1. Also, using the laser capture microdissection technique combined with RT-qPCR, we detected a substantial decrease in Pnoc but an increase in Oprl1 mRNA levels in the RMTg of Post-EtOH rats. Moreover, RMTg cFos expression is increased in Post-EtOH rats, which display anxiety- and depression-like behaviors. Intra-RMTg infusion of the endogenous NOP agonist nociceptin attenuates the aversive behaviors in Post-EtOH rats without causing any notable change in Naïve rats. Conversely, intra-RMTg infusion of the NOP selective antagonist [Nphe1]nociceptin(1-13)NH2 elicits anxiety- and depression-like behaviors in Naïve but not Post-EtOH rats. Furthermore, intra-RMTg infusion of nociceptin significantly reduces alcohol consumption. Thus, our results show that the deficiency of RMTg NOP signaling during alcohol withdrawal mediates anxiety- and depression-like behaviors. The intervention of NOP may help those individuals suffering from alcohol use disorders.

Childhood Trauma and Malevolent Creativity in Chinese College Students: Moderated Mediation by Psychological Resilience and Aggression.

Although a previous study has shown that childhood trauma influences malevolent creativity, aggression and psychological resilience have been linked with childhood trauma and creativity. However, little is known about the complex correlations among these factors in Chinese college students. The present study aimed to investigate the mediating role of aggression and the moderating role of psychological resilience between childhood trauma and malevolent creativity. A total of 389 undergraduates were enrolled in this cross-sectional study. The moderated mediation model was conducted to explore whether aggression mediated the correlation between childhood trauma and malevolent creativity and whether psychological resilience moderated the indirect role of childhood trauma. The results showed that childhood trauma positively correlated with aggression and malevolent creativity and was negatively associated with psychological resilience. Aggression partly mediated the association of childhood trauma with malevolent creativity. Resilience moderated the indirect effect of the mediation model, such that the indirect effect of childhood trauma on malevolent creativity through aggression increased as the level of resilience increased. The study indicated that childhood trauma exposure is associated with malevolent creativity behavior, and aggression mediated this association. The level of psychological resilience differentiates the indirect paths of childhood trauma on malevolent creativity. These results have important implications for preventing and containing expressions of malevolent creativity.

Comorbidity of Post-Traumatic Stress Disorder and Alcohol Use Disorder: Animal Models and Associated Neurocircuitry.

Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are prevalent neuropsychiatric disorders and frequently co-occur concomitantly. Individuals suffering from this dual diagnosis often exhibit increased symptom severity and poorer treatment outcomes than those with only one of these diseases. Lacking standard preclinical models limited the exploration of neurobiological mechanisms underlying PTSD and AUD comorbidity. In this review, we summarize well-accepted preclinical model paradigms and criteria for developing successful models of comorbidity. We also outline how PTSD and AUD affect each other bidirectionally in the nervous nuclei have been heatedly discussed recently. We hope to provide potential recommendations for future research.

Inhibition of heat shock protein family A member 8 attenuates spinal cord ischemia-reperfusion injury via astrocyte NF-κB/NLRP3 inflammasome pathway : HSPA8 inhibition protects spinal ischemia-reperfusion injury.

BACKGROUND: Astrocyte over-activation and extensive neuron loss are the main characteristic pathological features of spinal cord ischemia-reperfusion injury (SCII). Prior studies have placed substantial emphasis on the role of heat shock protein family A member 8 (HSPA8) on postischemic myocardial inflammation and cardiac dysfunction. However, it has never been determined whether HSPA8 participates in astrocyte activation and thus mediated neuroinflammation associated with SCII. METHODS: The left renal artery ligation-induced SCII rat models and oxygen-glucose deprivation and reoxygenation (OGD/R)-induced rat primary cultured astrocytes were established. The lentiviral vector encoding short hairpin RNA targeting HSPA8 was delivered to the spinal cord by intrathecal administration or to culture astrocytes. Then, the spinal neuron survival, gliosis, and nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome and its related pro-inflammatory cytokines were analyzed. RESULTS: SCII significantly enhanced the GFAP and HSPA8 expression in the spinal cord, resulting in blood-brain barrier breakdown and the dramatical loss of spinal neuron and motor function. Moreover, injury also increased spinal nuclear factor-kappa B (NF-κB) p65 phosphorylation, NLRP3 inflammasome-mediated caspase-1 activation, and subsequent interleukin (IL)-1ß as well as IL-18 secretion. Silencing the HSPA8 expression efficiently ameliorated the spinal cord tissue damage and promoted motor function recovery after SCII, through blockade of the astrocyte activation and levels of phosphorylated NF-κB, NLRP3, caspase-1, IL-1ß, and IL-18. Further in vitro studies confirmed that HSPA8 knockdown protected astrocytes from OGD/R-induced injury via the blockade of NF-κB and NLRP3 inflammasome activation. CONCLUSION: Our findings indicate that knockdown of HSPA8 inhibits spinal astrocytic damage after SCII, which may provide a promising therapeutic strategy for SCII treatment.

Endocannabinoid signaling in the lateral habenula regulates pain and alcohol consumption.

Hyperalgesia, which often occurs in people suffering from alcohol use disorder, may drive excessive drinking and relapse. Emerging evidence suggests that the lateral habenula (LHb) may play a significant role in this condition. Previous research suggests that endocannabinoid signaling (eCBs) is involved in drug addiction and pain, and that the LHb contains core components of the eCBs machinery. We report here our findings in rats subjected to chronic ethanol vapor exposure. We detected a substantial increase in endocannabinoid-related genes, including Mgll and Daglb mRNA levels, as well as monoacylglycerol lipase (MAGL) protein levels, as well as a decrease in Cnr1 mRNA and type-1 cannabinoid receptor (CB1R) protein levels, in the LHb of ethanol-exposed rats. Also, rats withdrawing from ethanol exposure displayed hypersensitivity to mechanical and thermal nociceptive stimuli. Conversely, intra-LHb injection of the MAGL inhibitor JZL184, the fatty acid amide hydrolase inhibitor URB597, or the CB1R agonist WIN55,212-2 produced an analgesic effect, regardless of ethanol or air exposure history, implying that alcohol exposure does not change eCB pain responses. Intra-LHb infusion of the CB1R inverse agonist rimonabant eliminated the analgesic effect of these chemicals. Rimonabant alone elicited hyperalgesia in the air-, but not ethanol-exposed animals. Moreover, intra-LHb JZL184, URB597, or WIN55,212-2 reduced ethanol consumption in both homecages and operant chambers in rats exposed to ethanol vapor but not air. These findings suggest that LHb eCBs play a pivotal role in nociception and facilitating LHb eCBs may attenuate pain in drinkers.

MicroRNA-137-3p Protects PC12 Cells Against Oxidative Stress by Downregulation of Calpain-2 and nNOS.

The imbalance between excess reactive oxygen species (ROS) generation and insufficient antioxidant defenses contribute to a range of neurodegenerative diseases. High ROS levels damage cellular macromolecules such as DNA, proteins and lipids, leading to neuron vulnerability and eventual death. However, the underlying molecular mechanism of the ROS regulation is not fully elucidated. Recently, an increasing number of studies suggest that microRNAs (miRNAs) emerge as the targets in regulating oxidative stress. We recently reported the neuroprotective effect of miR-137-3p for brachial plexus avulsion-induced motoneuron death. The present study is sought to investigate whether miR-137-3p also could protect PC12 cells against hydrogen peroxide (H2O2) induced neurotoxicity. By using cell viability assay, ROS assay, gene and protein expression assay, we found that PC-12 cells exposed to H2O2 exhibited decreased cell viability, increased expression levels of calpain-2 and neuronal nitric oxide synthase (nNOS), whereas a decreased miR-137-3p expression. Importantly, restoring the miR-137-3p levels in H2O2 exposure robustly inhibited the elevated nNOS, calpain-2 and ROS expression levels, which subsequently improved the cell viability. Furthermore, the suppressive effect of miR-137-3p on the elevated ROS level under oxidative stress was considerably blunted when we mutated the binding site of calpain-2 targted by miR-137-3p, suggesting the critical role of calpain-2 involving the neuroprotective effect of miR-137-3p. Collectively, these findings highlight the neuroprotective role of miR-137-3p through down-regulating calpain and NOS activity, suggesting its potential role for combating oxidative stress insults in the neurodegenerative diseases.

The Impact of Adverse Childhood Experiences on Mobile Phone Addiction in Chinese College Students: A Serial Multiple Mediator Model.

Mobile phone addiction is a universal phenomenon that has attracted a lot of attention in recent years. Previous researches revealed a significant relation between adverse childhood experiences (ACEs) and addiction. This study further investigated the association between ACEs and mobile phone addiction, and the mediating effects of attachment styles and interpersonal relationships. The cross-sectional design and multiple questionnaires, namely, the Revised Adverse Childhood Experience Questionnaire, the Mobile Phone Addiction Index, the Revised Adult Attachment Scale (AAS), and the Interpersonal Relationship Comprehensive Diagnostic Scale (IRCDS) were used in the sample of 345 university students. Correlation analysis revealed that adverse childhood experience, attachment anxiety, attachment avoidance, interpersonal relationship, and mobile phone addiction were significantly positively correlated with each other. Results of regression analysis showed that attachment style and interpersonal relationship played multiple mediation roles in the association between adverse childhood experience and mobile phone addiction. That is, (1) adverse childhood experience was positively related to mobile phone addiction, (2) both attachment anxiety and interpersonal relationship played partial and parallel mediating roles between adverse childhood experience and mobile phone addiction, and (3) attachment anxiety/avoidance and interpersonal relationship mediated the relationship between adverse childhood experience and mobile phone addiction sequentially. These results indicated that mobile phone addiction among college students who had adverse childhood experience can be relieved by way of the remission of attachment anxiety, reduction of attachment avoidance, and improvement of interpersonal relationship.

[A consensus on the standardization of the next generation sequencing process for the diagnosis of genetic diseases (3) - Data analysis].

Bioinformatic analysis and variant classification are the key components of high-throughput sequencing-based genetic diagnostic approach. This consensus is part of the effort to develop a standardized process for next generation sequencing (NGS)-based test for germline mutations underlying Mendelian disorders in China. The flow-chart, common software, key parameters of bioinformatics pipeline for data processing, annotation, storage and variant classification are reviewed, which is aimed to help improving and maintaining a high-quality process and obtaining consistent outcomes for NGS-based molecular diagnosis.

The Dual Role of Kinin/Kinin Receptors System in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive spatial disorientation, learning and memory deficits, responsible for 60%-80% of all dementias. However, the pathological mechanism of AD remains unknown. Numerous studies revealed that kinin/kinin receptors system (KKS) may be involved in the pathophysiology of AD. In this review article, we summarized the roles of KKS in neuroinflammation, cerebrovascular impairment, tau phosphorylation, and amyloid ß (Aß) generation in AD. Moreover, we provide new insights into the mechanistic link between KKS and AD, and highlight the KKS as a potential therapeutic target for AD treatment.

The protective effects of hydrogen sulfide on the myocardial ischemia via regulating Bmal1.

BACKGROUND: To investigate the effect of hydrogen peroxide (H2S) on myocardial clock gene Bmal1 in ischemic cardiomyocytes. MATERIALS & METHODS: Quantitative PCR (qPCR) was used to detect the expression of Bmal1 at the mRNA level in H9C2 rat cardiomyocytes. The protein expressions of Bax and Bcl-2, PI3K/Akt, caspase-3 were measured by western blotting. The levels of reactive oxygen species (ROS) were determined by ELISA. RESULTS: The expression level of clock gene Bmal1 demonstrated a clock rhythm of periodic oscillation within 24 h. Compared with the control group, H2S treatment maintained the rhythm of the clock gene in ischemic cardiomyocytes and increased the transcription and expression levels of Bmal1. H2S increased cell survival by activating PI3K/Akt signaling pathway, inhibiting mitochondrial apoptosis signaling, and reducing intracellular oxidative stress. PI3K/Akt and Bmal1 were demonstrated to be involved in H2S protection of cardiomyocyte ischemia. Knockout of Bmal1 gene affects the degree of phosphorylation of Akt and Erk proteins, and the level of ROS production, resulting in a decrease in the protective effects of H2S. CONCLUSION: The expression level of Bmal1 has effects on the function of cardiomyocytes such as ROS production. The potential mechanism by which H2S regulates clock genes may be related to the effect of clock genes on protein phosphorylation levels in ischemic cardiomyocytes.

Neuroanatomical Correlates of Creativity: Evidence From Voxel-Based Morphometry.

Creativity was a special cognitive capacity which was crucial to human survival and prosperity. Remote associates test (RAT), identifying the relationships among remote ideas, was one of the most frequently used methods of measuring creativity. However, the structural characteristics associated with RAT remains unclear. In the present study, the relationship between gray matter density (GMD)/white matter density (WMD) and RAT was explored using voxel-based morphometry (VBM) in a larger healthy college student sample (144 women and 117 men). Results showed that the score of RAT was significantly positively related with the GMD in the right anterior superior temporal gyrus (aSTG) and negatively correlated with the GMD in the right dorsal anterior cingulate cortex (dACC). Meanwhile, results also showed that the score of RAT was significantly positively related with the WMD in the right dACC and negatively correlated with the WMD in the left inferior frontal gyrus (IFG). These findings indicate that individual creativity, as measured by the RAT, was mainly related to the regional gray /white matter density of brain regions in the aSTG, dACC and IFG, which might have been involved in the forming of novel combinations, breaking of mental set, monitoring of conflict and semantic integration.

Investigation of copy number variations on chromosome 21 detected by comparative genomic hybridization (CGH) microarray in patients with congenital anomalies.

BACKGROUND: The clinical features of Down syndrome vary among individuals, with those most common being congenital heart disease, intellectual disability, developmental abnormity and dysmorphic features. Complex combination of Down syndrome phenotype could be produced by partially copy number variations (CNVs) on chromosome 21 as well. By comparing individual with partial CNVs of chromosome 21 with other patients of known CNVs and clinical phenotypes, we hope to provide a better understanding of the genotype-phenotype correlation of chromosome 21. METHODS: A total of 2768 pediatric patients sample collected at the Genetics Laboratory at Oklahoma University Health Science Center were screened using CGH Microarray for CNVs on chromosome 21. RESULTS: We report comprehensive clinical and molecular descriptions of six patients with microduplication and seven patients with microdeletion on the long arm of chromosome 21. Patients with microduplication have varied clinical features including developmental delay, microcephaly, facial dysmorphic features, pulmonary stenosis, autism, preauricular skin tag, eye pterygium, speech delay and pain insensitivity. We found that patients with microdeletion presented with developmental delay, microcephaly, intrauterine fetal demise, epilepsia partialis continua, congenital coronary anomaly and seizures. CONCLUSION: Three patients from our study combine with four patients in public database suggests an association between 21q21.1 microduplication of CXADR gene and patients with developmental delay. One patient with 21q22.13 microdeletion of DYRK1A shows association with microcephaly and scoliosis. Our findings helped pinpoint critical genes in the genotype-phenotype association with a high resolution of 0.1 Mb and expanded the clinical features observed in patients with CNVs on the long arm of chromosome 21.