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Methamphetamine, a commonly abused drug, is known for its high relapse rate. The persistence of addictive memories associated with methamphetamine poses a significant challenge in preventing relapse. Memory retrieval and subsequent reconsolidation provide an opportunity to disrupt addictive memories. However, the key node in the brain network involved in methamphetamine-associated memory retrieval has not been clearly defined. In this study, using the conditioned place preference in male mice, whole brain c-FOS mapping and functional connectivity analysis, together with chemogenetic manipulations of neural circuits, we identified the medial prefrontal cortex (mPFC) as a critical hub that integrates inputs from the retrosplenial cortex and the ventral tegmental area to support both the expression and reconsolidation of methamphetamine-associated memory during its retrieval. Surprisingly, with further cell-type specific analysis and manipulation, we also observed that methamphetamine-associated memory retrieval activated inhibitory neurons in the mPFC to facilitate memory reconsolidation, while suppressing excitatory neurons to aid memory expression. These findings provide novel insights into the neural circuits and cellular mechanisms involved in the retrieval process of addictive memories. They suggest that targeting the balance between excitation and inhibition in the mPFC during memory retrieval could be a promising treatment strategy to prevent relapse in methamphetamine addiction.
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BACKGROUND: Intraductal papillary neoplasms of the bile duct (IPNBs) are rare and characterized by papillary growth within the bile duct lumen. IPNB is similar to obstructive biliary pathology. In this report, we present an unexpected case of asymptomatic IPNB and consolidate our findings with the relevant literature to augment our understanding of this condition. Integrating relevant literature contributes to a more comprehensive understanding of the disease. CASE SUMMARY: A 66-year-old Chinese male patient was admitted to our hospital for surgical intervention after gallstones were discovered during a routine physical examination. Preoperative imaging revealed a lesion on the left side of the liver, which raised the suspicion of IPNB. A laparoscopic left hemihepatectomy was performed, and subsequent histopathological examination confirmed the diagnosis of IPNB. At the 3-mo postoperative follow-up, the patient reported good recovery and no metastasis. IPNB can manifest both latently and asymptomatically. Radical surgical resection is the most effective treatment for IPNB. CONCLUSION: Hepatic and biliary masses, should be considered to diagnose IPNB. Prompt surgery and vigilant follow-up are crucial in determining prognosis.
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The present study aimed to investigate the current situation of internet gaming disorder (IGD) in Chinese adolescents and explore the impact of IGD-related factors on adolescent aggression. We hypothesized that IGD symptoms in adolescents would be associated with aggressive behavior and that risk factors for IGD symptoms could increase the aggressive tendencies of adolescents. To verify the above hypothesis, a cross-sectional survey of junior and senior high school students from southern, southwestern, central, and eastern China was conducted. A total of 9306 valid questionnaires were collected. The results showed that the prevalence of IGD symptoms was 1.78 % among Chinese adolescents. The adolescents in the disordered gamer group had the most severe IGD symptoms, with the highest levels of psychological distress and aggression. Interestingly, adolescents in the casual gamer group had the lowest psychological distress and aggression scores. Linear regression analysis further showed that higher levels of aggression were significantly associated with male sex, younger age, more severe psychological distress and IGD symptoms, and more violent game exposure. Our results suggested that excessive online gaming not only contributes to psychological distress in adolescents but also increases their levels of aggressive behavior. Apart from male sex and younger age, severe IGD symptoms and psychological distress are the most important predictors of the development of aggressive behavior.
Subject(s)
Behavior, Addictive , Video Games , Humans , Male , Adolescent , Aggression , Cross-Sectional Studies , Internet Addiction Disorder/epidemiology , Behavior, Addictive/psychology , Video Games/psychology , InternetABSTRACT
Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer after hepatocellular carcinoma (HCC). ICC and HCC have different cellular origins; therefore, ICC is significantly different from HCC in terms of aetiology, mechanism, tumour biological behaviour, treatment methods, and prognosis. The objective of this study was to investigate the current incidence trend and prognosis of ICC and deepen the understanding of ICC. Methods: A large sample of ICC and HCC patient data was obtained from the Surveillance, Epidemiology and End Results (SEER) database of the National Cancer Institute (NCI), USA. The incidence trend, prognosis, and the effect of surgery and lymph node dissection on the prognosis of ICC patients were analysed. Results: In recent years, the incidence of ICC has increased. The treatment effect of ICC patients has been significantly improved. But the prognosis of ICC patients is significantly worse than that of HCC patients. Surgery can benefit all stages of ICC, and lymph node dissection is beneficial for the prognosis of patients with positive lymph nodes (N1). Conclusions: In recent years, the incidence of ICC has been increasing, and its prognosis remains poor, which is a cause for concern. We need to understand the epidemiological and pathophysiological characteristics of ICC and explore more effective treatment methods to improve the efficacy of treatment for ICC patients and prolong their survival.
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To identify the characteristics and sources of heavy metal pollution in the surrounding soil of a typical pyrite concentrated mining area in Anhui Province, the pH value and the concentrations of Zn, Cu, Cd, Pb, Cr, Ni, Hg, and As in 42 surface soil samples and 16 soil samples from two vertical sections in the study area were collected and measured. The distribution characteristics, pollution assessment, and source analysis of heavy metal elements were conducted using the ArcGis inverse distance weight interpolation method, Nemero comprehensive index method, principal component analysis method, and absolute factor score-multiple linear regression (APCS-MLR) receptor model. The results showed that the average concentration of the eight heavy metals was 1.03-13.14 times the background value in the Tongling area. The local enrichment of Zn, Cu, Cd, Pb, Hg, and As was obvious, and the spatial distribution was basically consistent with the location of man-made mining activities. The single-factor pollution index evaluation showed that Zn, Cu, Cd, Pb, and As had different degrees of pollution risk, and the pollution degree of Cd and Cu was the most serious, accounting for 47.62% and 42.86% of moderate pollution, respectively. The Nemerow comprehensive pollution index evaluation showed that 61.90% of the soil samples in the study area were moderately polluted. The ground accumulation index evaluation showed that the pollution degree of Zn, Cu, Cd, Pb, Hg, and As in the study area was mainly from light pollution to strong pollution. In the vertical soil profile variation, heavy metals were easily enriched in the surface layer of the soil but migrated slowly to the deep layer, with concentrations mainly above 1 m. The results of source analysis showed that the high geological background and mining contribution rates of Zn, Pb, and As were 37.82%, 43.49%, and 46.63%, respectively. The natural contribution rates of weathering of parent material were 34.02%, 40.88%, and 38.52%, respectively. The sources of Cr and Ni were mainly natural sources of weathering of the parent material, with contribution rates of 91.95% and 73.68%, respectively. Geological high background and mining activities contributed 41.91% of the Cu sources, and atmospheric sedimentation and agricultural comprehensive sources contributed 41.30%. There were many sources of Hg. The natural source of weathering of soil parent material contributed 35.60%, geological high background and mining activities contributed 29.87%, and unknown sources contributed 34.05%. The main source of Cd was atmospheric sedimentation and agricultural comprehensive sources, contributing 81.81%.
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BACKGROUND: Paragangliomas are rare neuroendocrine tumors. We hereby report a case of a localized paraganglioma found in the abdominal cavity, and review the relevant literature to improve the understanding of this disease. CASE SUMMARY: A 29-year-old Chinese female patient was referred to our hospital due to an abdominal mass found on physical examination. Imaging revealed a mass in the left upper abdomen, suggestive of either a benign stromal tumor or an ectopic accessory spleen. Laparoscopic radical resection was subsequently performed, and histopathological analysis confirmed the diagnosis of a paraganglioma. The patient was followed up 3 months post-operation, and reported good recovery with no metastasis. CONCLUSION: Radical resection can effectively treat intra-abdominal paragangliomas, with few side effects and low recurrence risk. In addition, early and accurate diagnosis and timely intervention are essential for the prognosis of this disease.
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Introduction: Fear memory generalization is regarded as the core characteristic of posttraumatic stress disorder (PTSD) development. However, the mechanism that contributes to the generalization of conditioned fear memory is still unclear. The generalization is generally considered to be a mismatch that occurs during memory consolidation. Methods: Foot shocks and tones were given as unconditioned stress and conditioned stress, respectively for fear conditioning training. Immunofluorescence staining, western blotting and qPCR were performed to determine the expression of different genes in amygdala of mice after fear conditioning training. Cycloheximide was used as a protein synthesis inhibitor and 2-methyl-6-phenylethynyl-pyridine was injected for mGluR5 inhibition. Results: Fear conditioning using caused incremental generalization, which was clearly observed during training. The density of c-Fos+ cells or the synaptic p-NMDAR expression did not differ with stress intensities. Strong-shock fear conditioning could induce significant mGluR5 de novo synthesis in the amygdala, which was not observed in the weak-shock group. Inhibition of mGluR5 impaired fear memory generalization induced by strong-shock fear conditioning, but the generalization level induced by weak-shock training was enhanced. Discussion: These results indicated that mGluR5 in the amygdala is critical to the function of inappropriate fear memory generalization and suggested that this may be a potential target for the treatment of PTSD.
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In December 2019, coronavirus disease 2019 (COVID-19) appeared in Wuhan (Hubei, China) and subsequently swept the globe. In addition to the risk of infection, there is a strong possibility that post-traumatic stress disorder (PTSD) may be a secondary effect of the pandemic. Health care workers (HCWs) participating in the pandemic are highly exposed to and may bear the brunt out of stressful or traumatic events. In this cross-sectional study, we assessed the morbidity and risk factors of PTSD symptoms among Chinese HCWs. A total of 457 HCWs were recruited from March 15, 2020, to Mach 22, 2020, including HCWs in Wuhan and Hubei Province (excluding Wuhan), the areas first and most seriously impacted by COVID-19. The morbidity of PTSD symptoms was assessed by the Event Scale-Revised (IES-R). The risk factors for PTSD symptoms were explored by means of logistic regression analysis. Over 40% of the respondents experienced PTSD symptoms more than one month after the COVID-19 outbreak, and this proportion increased to 57.7% in Wuhan HCWs, especially females and HCWs on the frontline. Thus, rapid mental health assessment and effective psychological interventions need to be developed for frontline HCWs to prevent long-term PTSD-related disabilities. Moreover, Negative coping style and neuroticism personality may be regarded as high risk factors for PTSD symptoms. Improving individual coping strategies to enhance resilience should be the focus of further preventive intervention strategies.
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Objective: This study examined the prevalence of posttraumatic stress disorder (PTSD) symptoms in college students 1 month after the lockdown of Wuhan to identify possible risk factors for PTSD symptoms in a cross-sectional study. Methods: Out of 10,502 who responded, 9,274 students impacted by the COVID-19 pandemic were included in our study. PTSD symptoms was evaluated by the Impact of Event Scale-revised (IES-R). Anxiety/depression symptoms were evaluated by the Kessler Psychological Distress Scale (K10). Personality traits, coping style, and social support were assessed by the Eysenck Personality Questionnaire-Revised Short Scale for Chinese (EPQ-RSC), the Simplified Coping Style Questionnaire (SCSQ), and the Social Support Rating Scale (SSRS). Logistic regression analysis was utilized to further explore risk factors for PTSD symptoms. Results: More than 1 month after the COVID-19 outbreak, 13.1% of college students developed PTSD symptoms, indicating that COVID-19 associated stressful experiences were connected with PTSD symptoms. After the COVID-19 outbreak, subjects with symptomatologic PTSD symptoms were more likely to experience strained relationships with their family, to have close contact with COVID-19 patients and to drop out of college. The logistic regression model demonstrated the association factors of PTSD symptoms. Neuroticism, psychoticism and an avoidant coping style were associated with increased risk for PTSD symptoms, while an active coping style was protective against PTSD symptoms during this pandemic. Conclusion: The results showed that PTSD symptoms was prevalent in Chinese college students 1 month after the COVID-19 outbreak. Effective psychological support work should be carried out accordingly.
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In this study, the variational method concerning displacement components is applied to solve the large deformation problem of a thin cylindrical shell with its four sides fully fixed and under uniformly distributed loads, in which the material that constitutes the shell has a bimodular effect, in comparison to traditional materials, that is, the material will present different moduli of elasticity when it is in tension and compression. For the purpose of the use of the displacement variational method, the physical equations on the bimodular material model and the geometrical equation under large deformation are derived first. Thereafter, the total strain potential energy is expressed in terms of the displacement component, thus bringing the possibilities for the classical Ritz method. Finally, the relationship between load and central deflection is obtained, which is validated with the numerical simulation, and the jumping phenomenon of thin cylindrical shell with a bimodular effect is analyzed. The results indicate that the bimodular effect will change the stiffness of the shell, thus resulting in the corresponding change in the deformation magnitude. When the shell is relatively thin, the bimodular effect will influence the occurrence of the jumping phenomenon of the cylindrical shell.
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Fear memory is critical for individual survival. However, the maladaptive fear response is one of the hallmarks of fear-related disorders, which is characterized by the failure to discriminate threatening signals from neutral or safe cues. The biological mechanisms of fear discrimination remain to be clarified. In this study, we found that the nucleus accumbens (NAc) was indispensable for the formation of cued fear memory in mice, during which the expression of DNA methyltransferase 3a gene (DNMT3a) increased. Injection of Zebularine, a nonspecific DNMT inhibitor, into NAc immediately after conditioning induced a maladaptive fear response to neutral cue (CS-). Using whole-genome bisulfite sequencing (WGBS), differentially methylated sites and methylated regions (DMRs) were investigated. 16,226 DMRs in the genenome were identified, in which, 214 genes with significant differences in their methylation levels and mRNA expression profiles were identified through correlation analysis. Notably, 15 genes were synaptic function-related and 8 genes were enriched in the cGMP-PKG signaling pathway. Moreover, inhibition of PKG impaired fear discrimination. Together, our results revealed the profile and role of genome-wide DNA methylation in NAc in the regulation of fear discrimination.
Subject(s)
DNA Methylation , Nucleus Accumbens , Animals , Mice , RNA-Seq , Fear , RNA, MessengerABSTRACT
Stress-induced neuroepigenetic programming gains growing more and more interest in the studies of the etiology of posttraumatic stress disorder (PTSD). However, seldom attention is focused on DNA demethylation in fear memory generalization, which is the core characteristic of PTSD. Here, we show that ten-eleven translocation protein 3 (TET3), the most abundant DNA demethylation enzyme of the TET family in neurons, senses environmental stress and bridges neuroplasticity with behavioral adaptation during fear generalization. Foot shock strength dependently induces fear generalization and TET3 expression in nucleus accumbens (NAc) in mice. Inhibition of DNA demethylation by infusing demethyltransferase inhibitors or AAV-Tet3-shRNA virus in NAc enhances the fear generalization and anxiety-like behavior. Furthermore, TET3 knockdown impairs the dendritic spine density, PSD length, and thickness of neurons, decreases DNA hydroxymethylation (5hmC), reduces the expression of synaptic plasticity-related genes including Homer1, Cdkn1a, Cdh8, Vamp8, Reln, Bdnf, while surprisingly increases immune-related genes Stat1, B2m, H2-Q7, H2-M2, C3, Cd68 shown by RNA-seq. Notably, knockdown of TET3 in NAc activates microglia and CD39-P2Y12R signaling pathway, and inhibition of CD39 reverses the effects of TET3 knockdown on the fear memory generalization and anxiety. Overexpression of TET3 by Crispr-dSaCas9 virus delivery to activate endogenous Tet3 in NAc increases dendritic spine density of neurons in NAc and reverses fear memory generalization and anxiety-like behavior in mice. These results suggest that TET3 modulates fear generalization and anxiety via regulating synaptic plasticity and CD39 signaling pathway.
Subject(s)
Anxiety , Dioxygenases , Fear , Nucleus Accumbens , Animals , Mice , Dioxygenases/genetics , Dioxygenases/metabolism , Neuronal Plasticity , Nucleus Accumbens/metabolism , Signal TransductionABSTRACT
Post-traumatic stress disorder (PTSD) is a devastating mental illness with high morbidity and major social and economic burden. Currently, there is no promising therapy available for the treatment of PTSD. Some clinical studies showed that ketamine could effectively alleviate PTSD symptoms. However, it is still unclear which brain region ketamine targets and how it attenuates the PTSD-like effects. In this study, we examined the effect of ketamine on fear generalization (a core symptom of PTSD) by using a mice model of fear generalization induced by fear conditioning procedure. Before retrieval, ketamine was locally infused into the nucleus accumbens (a brain region closely associated with PTSD). Fear generalization mice were subjected to behavioral testing and biochemical assessments, following ketamine infusion. The results showed that the foot shock strength-dependently induced fear generalization in mice with increased c-fos activity, and a lower level of GluR1(S845), GluR1(S831) protein, and a higher level of P-GluN2B protein in the nucleus accumbens (NAc). Local infusion of ketamine into NAc decreased the fear generalization together with an increased level of GluR1(S845), GluR1(S831) protein, and decreased level of P-GluN2B protein. Altogether, these results conclude that ketamine might affect the glutamatergic signaling in the NAc to attenuate the fear generalization in mice.
Subject(s)
Ketamine , Stress Disorders, Post-Traumatic , Animals , Fear/physiology , Generalization, Psychological/physiology , Humans , Ketamine/pharmacology , Mice , Nucleus Accumbens , Stress Disorders, Post-Traumatic/drug therapyABSTRACT
AIM: To identify mutations with whole exome sequencing (WES) in a Chinese X-linked retinitis pigmentosa (XLRP) family. METHODS: Patients received the comprehensive ophthalmic evaluation. Genomic DNA was extracted from peripheral blood and subjected to SureSelect Human All Exon 6+ UTR exon capture kit. The exons were sequenced as 100 base paired reads on Illumina HiSeq2500 system. Only mutations that resulted in a change in amino acid sequence were selected. A pattern of inheritance of the RP family was aligned to identified causal mutation. RESULTS: We analysed the data of WES information from XLRP family. The analysis revealed a hemizygous large genomic deletion of RPGR c.29_113del was responsible for this XLRP. The gross deletion lead to a frame-shift mutation and generate stop codon at 7 animo acid behind Asp (D10Afs*7), which would serious truncate RPGR protein. The novel frame-shift mutation was found to segregate with retinitis pigmentosa (RP) phenotype in this family. Bilateral myopia was present on the male patients, but carrier female showed unilateral myopia without RP. CONCLUSION: Our study identifies a novel frame-shift mutation of RPGR in a Chinese family, which would expand the spectrum of RPGR mutations. The geno-phenotypic analysis reveals a correlation between RP and myopia. Although exact mechanism of RP related myopia is still unknown, but the novel frame-shift mutation will give our hit on studying the molecular pathogenesis of RP and myopia.
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Hepatic injury is one of the most challenging diseases in clinical medicine. Hepatic injury is accompanied by hepatocyte apoptosis and leads to hepatic fibrosis and cirrhosis, which may cause liver cancer and increased mortality. Therefore, it is essential to investigate the regulation mechanism and therapeutic strategies for hepatic injury. In the study, the effects of Thymosin ß4 (Tß4) on Long intergenic noncoding RNA-p21 (lincRNA-p21)-mediated liver injury were investigated. Results showed that lincRNA-p21 overexpression promoted hepatocytes apoptosis, which was blocked by Tß4. Besides, Tß4 reversed the levels of cleaved caspase-3 and caspase-9 induced by lincRNA-p21. LincRNA-p21 overexpression also caused the pathological injury and fibrosis in hepatic tissues and increased the levels of fibrosis-related proteins (Collagen I, α-SMA and TIMP-1), and induced hydroxyproline and ALT production. However, Tß4 reversed the effects of overexpression of lincRNA-p21 on hepatic injury and fibrosis. In vitro experiments, after lincRNA-p21 was overexpressed in hepatic stellate cells (HSCs), the proliferation ability and the levels of HSCs markers α-SMA and Desmin were increased. However, Tß4 reversed the effects of lincRNA-p21 on HSCs. Furthermore, the PI3K-AKT-NF-κB pathway was activated by lincRNA-p21, which was then reversed by the Tß4 administration. After the mice treated by insulin-like growth factor-1 (IGF-1) (the activator of PI3K-AKT), the inhibitory effect of Tß4 on activated the PI3K-AKT-NF-κB pathway was abrogated. Besides, IGF-1 abolished the protective effects of Tß4 on hepatic apoptosis and fibrosis induced by lincRNA-p21. Therefore, Tß4 reversed. lincRNA-p21-mediated liver injury through inhibiting PI3K-AKT-NF-κB pathway. Tß4 may be a promising drug for fibrosis therapy.
Subject(s)
Apoptosis/drug effects , Liver Cirrhosis/prevention & control , Liver/injuries , RNA, Long Noncoding/genetics , Thymosin/pharmacology , Actins/metabolism , Animals , Cell Proliferation/drug effects , Collagen/metabolism , Hepatocytes/pathology , I-kappa B Proteins/antagonists & inhibitors , Liver/metabolism , Liver Cirrhosis/drug therapy , Mice , Mice, Inbred C57BL , Phosphatidylinositol 3-Kinases/metabolism , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Tissue Inhibitor of Metalloproteinase-1/metabolismABSTRACT
The adsorption and wetting on quartz surfaces by aqueous solutions of xylyl-substituted biquaternary ammonium salt gemini surfactants with different spacer groups (C3 and C6), have been investigated. The interfacial properties of surfactant solutions such as contact angle, adhesional tension (γLV cos θ), quartz-water interfacial tension (γSL) as well as adhesion work (WA) have been estimated. The obtained results show that C3 and C6 have similar adsorption behavior on quartz surfaces. Before critical micelle concentration (cmc) is reached, the contact angles of gemini surfactants slowly increase with the increasing concentration, and the adsorption amount at the water-air interface is almost the same as those at a quartz-water interface. After reaching cmc, the gemini surfactant Cn molecules form a more compact adsorption film through bending the flexible spacer chain, instead of forming a bi-layer. As a result, a further increase in quartz-liquid interfacial tension (γSL) and a consequent increase in contact angle have been observed after cmc. Gemini C6 shows a stronger ability towards hydrophobic modification at a quartz surface than C3, demonstrating the contribution of the longer methylene spacer to the hydrophobic modification of the quartz surface.
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Fear memories are critical for survival. Nevertheless, over-generalization of these memories, depicted by a failure to distinguish threats from safe stimuli, is typical in stress-related disorders. Previous studies have supported a protective role of ketamine against stress-induced depressive behavior. However, the effect of ketamine on fear generalization remains unclear. In this study, we investigated the effects of ketamine on fear generalization in a fear-generalized mouse model. The mice were given a single sub-anesthetic dose of ketamine (30 mg/kg, i.p.) 1 h before, 1 week before, immediately after, or 22 h after fear conditioning. The behavioral measure of fear (indicated by freezing level) and synaptic protein expression in the basolateral amygdala (BLA) and inferior-limbic pre-frontal cortex (IL-PFC) of mice were examined. We found that only ketamine administered 22 h after fear conditioning significantly decreased the fear generalization, and the effect was dose-dependent and lasted for at least 2 weeks. The fear-generalized mice showed a lower level of brain-derived neurotrophic factor (BDNF) and a higher level of GluN2B protein in the BLA and IL-PFC, and this was reversed by a single administration of ketamine. Moreover, the GluN2B antagonist ifenprodil decreased the fear generalization when infused into the IL-PFC, but had no effect when infused into the BLA. Infusion of ANA-12 (an antagonist of the BDNF receptor TrkB) into the BLA or IL-PFC blocked the effect of ketamine on fear generalization. These findings support the conclusion that a single dose of ketamine administered 22 h after fear conditioning alleviates the fear memory generalization in mice and the GluN2B-related BDNF signaling pathway plays an important role in the alleviation of fear generalization.
Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Conditioning, Classical/drug effects , Fear/drug effects , Ketamine/pharmacology , Receptors, N-Methyl-D-Aspartate/metabolism , Amygdala/metabolism , Animals , Male , Mice , Mice, Inbred C57BL , Prefrontal Cortex/metabolism , Signal Transduction/drug effectsABSTRACT
Long-term overuse of grasslands results in quantitative and qualitative decline of forage yield. Nutrient supplementation is a key strategy to improve forage yield. While mounting evidence showed that nitrogen (N) supplementation can increase forage yield, little is known about its impacts on forage quality. To understand the effects of N supplementation on forage quality at the community level, we carried out a field experiment in the meadow steppe of Hulunbuir. Our results showed that N supplementation significantly increased forage yield by 23%, which was mainly due to positive responses of perennial rhizomatous grass. The yield of other plant functional groups showed neutral response to N supplementation. The concentrations of crude protein, crude fat, and crude fiber varied significantly among different plant functional groups. Nitrogen supplementation significantly enhanced the concentration of crude protein in rhizomatous grass, bunchgrass, legume, and sedge. It enhanced the content of crude fat in rhizomatous grass but with no effect on other functional groups. Nitrogen supplementation had no effect on the concentration of crude fibre in all functional groups. At the community level, N supplementation significantly increased the concentrations of crude protein and crude fat. Our results are important for understanding the responses of forage production in meadow steppe under the scenarios of N enrichment.
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Grassland , Nitrogen , Poaceae , China , FertilizersSubject(s)
Anesthesia, Epidural/adverse effects , Anesthesia, Spinal/adverse effects , Cesarean Section/adverse effects , Dexmedetomidine/therapeutic use , Nalbuphine/therapeutic use , Shivering , Adult , Blood Glucose/metabolism , Dexmedetomidine/pharmacology , Female , Humans , Insulin/blood , Nalbuphine/pharmacology , Postoperative Complications/etiology , Pregnancy , Shivering/drug effects , Time Factors , Treatment Outcome , Uterine Contraction/drug effects , Visual Analog ScaleABSTRACT
BACKGROUND: Fear renewal, the context-specific relapse of a conditioned fear after extinction, is a widely pursued model of post-traumatic stress disorder and phobias. However, its cellular and molecular mechanisms remain poorly understood. The dentate gyrus (DG) has emerged as a critical locus of plasticity with relevance to memory, anxiety disorders, and depression, and it contributes to fear memory retrieval. Here, we have identified the role of the DG in fear renewal and its molecular mechanism. MATERIALS AND METHODS: Muscimol (MUS), activator of cyclic adenosine monophosphate (cAMP) forskolin (FSK), inhibitor of protein kinase A (PKA), Rip-cAMP, and a phosphodiesterase inhibitor rolipram were infused into DG of standard deviation rats before renewal testing. cAMP levels after fear renewal was measured by enzyme-linked immunosorbent assay. The protein levels of phosphodiesterase 4 (PDE4) isoforms were tested by western blot. At last, the roles of cAMP signaling were also tested in the acquisition of fear conditioning, fear retrieval, and extinction. RESULTS: Intra-DG treatment of MUS and Rp-cAMP impaired fear renewal. FSK and rolipram exhibited the opposite effect, which also occurred in the retrieval of original fear memory. This change in fear renewal was regulated by PDE4 isoforms PDE4A, PDE4A5, and PDE4D. In addition, FSK and rolipram facilitated the acquisition of fear conditioning in long-term memory, but not short-term memory, while Rp-cAMP impaired long-term memory. For extinction, FSK and rolipram inhibited extinction process, while Rp-cAMP facilitated fear extinction. CONCLUSION: These findings demonstrated that fear renewal activated cAMP signaling in the DG through decreased PDE4 activity. Because of the role of cAMP signaling in the acquisition or retrieval of fear conditioning and encoding of extinction, it is speculated that initial learning and extinction may have similarities in molecular mechanism, especially fear retrieval and fear renewal may share cAMP signaling pathway in the DG.