Background:Machine learning to predict morbidity and mortality-especially in a population traditionally considered low risk-has not been previously examined.We sought to characterize the incidence of death among patie...Background:Machine learning to predict morbidity and mortality-especially in a population traditionally considered low risk-has not been previously examined.We sought to characterize the incidence of death among patients with a low estimated morbidity and mortality risk based on the National Surgical Quality Improvement Program(NSQIP)estimated probability(EP),as well as develop a machine learning model to identify individuals at risk for“unpredicted death”(UD)among patients undergoing hepatopancreatic(HP)procedures.Methods:The NSQIP database was used to identify patients who underwent elective HP surgery between 2012-2017.The risk of morbidity and mortality was stratified into three tiers(low,intermediate,or high estimated)using a k-means clustering method with bin sorting.A machine learning classification tree and multivariable regression analyses were used to predict 30-day mortality with a 10-fold cross validation.C statistics were used to compare model performance.Results:Among 63,507 patients who underwent an HP procedure,median patient age was 63(IQR:54-71)years.Patients underwent either pancreatectomy(n=38,209,60.2%)or hepatic resection(n=25,298,39.8%).Patients were stratified into three tiers of predicted morbidity and mortality risk based on the NSQIP EP:low(n=36,923,58.1%),intermediate(n=23,609,37.2%)and high risk(n=2,975,4.7%).Among 36,923 patients with low estimated risk of morbidity and mortality,237 patients(0.6%)experienced a UD.According to the classification tree analysis,age was the most important factor to predict UD(importance 16.9)followed by preoperative albumin level(importance:10.8),disseminated cancer(importance:6.5),preoperative platelet count(importance:6.5),and sex(importance 5.9).Among patients deemed to be low risk,the c-statistic for the machine learning derived prediction model was 0.807 compared with an AUC of only 0.662 for the NSQIP EP.Conclusions:A prognostic model derived using machine learning methodology performed better than the NSQIP EP in predicting 30-day UD among low risk patients undergoing HP surgery.展开更多
Climate models are essential for understanding past,present,and future changes in atmospheric circulation,with circulation modes providing key sources of seasonal predictability and prediction uncertainties for both g...Climate models are essential for understanding past,present,and future changes in atmospheric circulation,with circulation modes providing key sources of seasonal predictability and prediction uncertainties for both global and regional climates.This study assesses the performance of models participating in phase 6 of the Coupled Model Intercomparison Project in simulating interannual variability modes of Northern Hemisphere 500-hPa geopotential height during winter and summer,distinguishing predictable(potentially predictable on seasonal or longer timescales)and unpredictable(intraseasonal and essentially unpredictable at long range)components,using reanalysis data and a variance decomposition method.Although most models effectively capture unpredictable modes in reanalysis,their ability to reproduce dominant predictable modes-specifically the Pacific-North American pattern,Arctic Oscillation,and Western Pacific Oscillation in winter,and the East Atlantic and North Atlantic Oscillations in summer-varies notably.An optimal ensemble is identified to distinguish(a)predictable-external modes,dominated by external forcing,and(b)predictable-internal modes,associated with slow internal variability,during the historical period(1950-2014)and the SSP5-8.5 scenario(2036-2100).Under increased radiative forcing,the leading winter/summer predictable-external mode exhibits a more uniform spatial distribution,remarkably larger trend and annual variance,and enhanced height-sea surface temperature(SST)covariance under SSP5-8.5 compared to historical conditions.The dominant winter/summer predictable-internal modes also exhibit increased variance and height-SST covariance under SSP5-8.5,along with localized changes in spatial configuration.Minimal changes are observed in spatial distribution or variance for dominant winter/summer unpredictable modes under SSP5-8.5.This study,from a predictive perspective,deepens our understanding of model uncertainties and projected changes in circulations.展开更多
“As a global citizen,I speak to you with fear.I fear increasing unpredictability and fragmentation that can easily result in conflict.And in conflict,no one wins-we all lose,”Matias Acosta,CEO of Italian cleantech f...“As a global citizen,I speak to you with fear.I fear increasing unpredictability and fragmentation that can easily result in conflict.And in conflict,no one wins-we all lose,”Matias Acosta,CEO of Italian cleantech firm Cosysense,told the audience at the China Today•Macao Salon dialogue in Hengqin,south China’s Guangdong Province,on July 27,2025.展开更多
Under natural conditions, organisms regularly experience seasonal or unpredictable fluctuations in their diet that may shape the quantity and quality of their reproduction. While these dietary shifts are known to infl...Under natural conditions, organisms regularly experience seasonal or unpredictable fluctuations in their diet that may shape the quantity and quality of their reproduction. While these dietary shifts are known to influence overall reproductive output, their specific effects on the proportional composition of egg components remain unexplored. To partially simulate the natural conditions, we conducted two trials using adult Japanese Quails (Coturnix japonica) to examine how dietary restriction and unpredictable feeding influence the proportional composition of egg components. In the first trial, quails were assigned to one of four treatments: full-fed (control) or restricted feeding at 20% (DR20), 30% (DR30), and 40% (DR40) below daily intake. In the second trial, quails were assigned to one of three treatments: full feeding (control), constant 40% restriction (DR40), or unpredictable feeding schedule (UNPR). Each trial lasted for 14 days, and birds were housed individually. Severe dietary restrictions (DR30, DR40) reduced albumen and shell mass, shell thickness, and egg volume. However, yolk mass, yolk color, egg shape index, and shell density remained unaffected across all dietary levels. Severe restrictions also increased the yolk ratio while reducing the albumen ratio, suggesting that birds may evolutionarily prioritize yolk deposition to sustain reproductive functions. However, reduced albumen content due to maternal nutritional stress may also limit essential nutrients, and disrupt the embryo's osmoregulation, which ultimately affects offspring quality. Reduced shell contents at the severe restriction levels can affect the egg's ability to provide physical protection, regulate gas exchange and control water loss, thereby influencing embryonic development. In contrast, moderate restriction (DR20) and unpredictable feeding (UNPR) had no effect on any of the egg traits. These findings suggest that quails strategically allocate resources among egg components under dietary constraints, indicating potential trade-offs in reproductive investment. The resilience observed under moderate restriction and unpredictability underscores the species' adaptive capacity in fluctuating environments.展开更多
Background:Childhood environmental unpredictability(CEU)is crucial to personal development,profoundly influence physical and psychological growth particularly,and psychopathy is recognized as a dark personality trait....Background:Childhood environmental unpredictability(CEU)is crucial to personal development,profoundly influence physical and psychological growth particularly,and psychopathy is recognized as a dark personality trait.The aim of this study is to investigate the effects of insecure attachment and life history strategy(LHS)on the relationship between CEU and psychopathy by establishing a sequential mediation model based on evolutionary life history theory and cognitive-affective personality system.Methods:A group of 532 undergraduates completed the measurements for CEU,insecure attachment,LHS,and psychopathy,and Bootstrap mediation test through SPSS 25.0 and PROCESS macro tool was used to examine the relationship among these variables.Results:The results revealed positive relations between CEU and insecure attachment(β=0.87,p<0.001),CEU and LHS(β=0.11,p<0.001),and CEU and psychopathy(β=0.14,p<0.001).Insecure attachment was also positively associated with LHS(β=0.62,p<0.001)and psychopathy(β=0.04,p<0.001).In addition,LHS was significantly associated with psychopathy(β=0.08,p<0.001).The relationship between CEU and psychopathy is mediated independently and sequentially by insecure attachment and LHS.Conclusion:The current research shows the relationship between CEU and psychopathy,as well as the mechanism of insecure attachment and life history strategy as mediators.展开更多
Objective:To evaluate the effects of Wuhua herbal tea on chronic unpredictable mild stress(CUMS)-induced depression and explore its mechanism of action in combating depression.Methods:We tested the antidepressant effe...Objective:To evaluate the effects of Wuhua herbal tea on chronic unpredictable mild stress(CUMS)-induced depression and explore its mechanism of action in combating depression.Methods:We tested the antidepressant effects of Wuhua herbal tea in a rat model of CUMS-induced depression using fluoxetine as a positive control.The rats were divided into four groups:control group,model group,fluoxetine group,and Wuhua herbal tea group.The rats underwent body weight measurements,sucrose preference test,and open-field test.Enzyme-linked immunosorbent assay kits were used to detect the serum levels of serotonin,dopamine,adrenocorticotropic hormone(ACTH),corticosterone,norepinephrine,and interleukin-6.Intergroup comparisons and detection of brain-derived neurotrophic factor(BDNF),cAMP-response element binding protein(CREB),Janus kinase 2(JAK2),and signal transducer and activator of transcription 3(STAT3)mRNA expression in the hippocampus were performed using RTPCR.Immunohistochemistry was used to identify the expression of phosphorylated JAK2(p-JAK2)and phosphorylated STAT3(p-STAT3)proteins in hippocampal paraffin sections of CUMS rats.Results:Compared with the control group,the model group rats had depressive tendencies,exhibiting low vitality and interest in various behavioral indicators which were signs of despair.The Wuhua herbal tea group statistically increased the levels of serotonin and dopamine in the serum of CUMS rats to varying degrees(P=.015 and P=.002);reduced serum levels of ACTH,corticosterone,norepinephrine,and interleukin-6(all P<.05);and decreased mRNA expression of BDNF,CREB,JAK2,and STAT3 in the hippocampus(all P<.05);and decreased p-STAT3 protein levels(P=.006).Conclusion:Wuhua herbal tea shows antidepressant potential in CUMS rats by modulating the HPA axis and inhibiting JAK2-STAT3 overactivation,alleviating neuroinflammation.It also restores BDNF-CREB pathway function,reducing depressive symptoms.展开更多
Background Major depressive disorder(MDD),characterised by persistent anhedonia and elevated suicide risk,represents a global mental health challenge.Recent studies suggest a link between gut-brain axis dysfunction an...Background Major depressive disorder(MDD),characterised by persistent anhedonia and elevated suicide risk,represents a global mental health challenge.Recent studies suggest a link between gut-brain axis dysfunction and depression.The natural compound paeoniflorin demonstrates clinically relevant antidepressant effects,yet its underlying neurobiological mechanisms remain elusive.Aims This study aims to examine how paeoniflorin alleviates depression-like behaviours in rats subjected to chronic unpredictable mild stress(CUMS)by modulating the function of gut-brain axis,and explore the connections between gut microbiota,metabolites and MDD.Methods Depression-like behaviours in rats were induced by CUMS,and the antidepressant effect of paeoniflorin was assessed using behavioural tests.The composition and function of the intestinal microbiota were analysed using 16S rRNA sequencing,and metabolomic analysis was performed on serum,hippocampus,jejunum and faecal samples.Enzyme-linked immunosorbent assay and hematoxylin and eosin staining were used to detect the levels of inflammatory factors and cortisol,as well as the infiltration of inflammatory cells in the jejunum of rats after cohousing.Long-term potentiation assays and Golgi staining were used to detect dendritic spine density and synaptic plasticity,respectively.Results Paeoniflorin significantly alleviated depression-like behaviours and cognitive deficits in CUMS rats.16S rRNA sequencing revealed that paeoniflorin improved the abundance and diversity of the gut microbiota in CUMS rats.Enrichment of differential metabolites in the brain,intestine,faeces and serum revealed a primary accumulation in the amino acid metabolism pathway.We further observed a correlation between the relative abundance of microbial communities and metabolites.Cohousing experiments verified that microbial metabolites of paeoniflorin can reduce neuroinflammation and improve synaptic plasticity.Conclusions Disruptions in gut microbiota and its metabolites impair gut-brain interactions.Paeoniflorin’s neuroprotective and antidepressant effects are mediated through the modulation of the function of the gut-brain axis.展开更多
Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to stressors.In the present study,the effect of chronic unpredictable mild stress（CUMS）on ...Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to stressors.In the present study,the effect of chronic unpredictable mild stress（CUMS）on CRH neurons was investigated in rat brain.Methods The rats were exposed to one of the stressors each day for 21 d.Immunostaining was performed to detect the CRH-positive neurons in the paraventricular nucleus（PVN）of the hypothalamus and in amygdala.Results After the stress protocol,the animals showed a reduction in body weight gain as well as reduced sucrose preference and locomotor activity.Interestingly,the CRH neurons in both PVN and central nucleus of the amygdala（CeA）were stimulated by CUMS.The densities of CRH-containing neurons in both PVN and CeA were significantly higher than those in control group.Conclusion The CRH systems in PVN and CeA may both contribute to depression-like behaviors during CUMS.展开更多
This paper analyzes a problem processing mechanism in a new collaboration system between the main manufacturer and the supplier in the"main manufacturer-supplier"mode,which has been widely applied in the col...This paper analyzes a problem processing mechanism in a new collaboration system between the main manufacturer and the supplier in the"main manufacturer-supplier"mode,which has been widely applied in the collaborative development management of the complex product.This paper adopts the collaboration theory,the evolutionary game theory and numerical simulation to analyze the decision-making mechanism where one upstream supplier and one downstream manufacturer must process an unpredicted problem without any advance contract in common.Results show that both players'decision-makings are in some correlation with the initial state,income impact coefficients,and dealing cost.It is worth noting that only the initial state influences the final decision,while income impact coefficients and dealing cost just influence the decision process.This paper shows reasonable and practical suggestions for the manufacturer and supplier in a new collaboration system for the first time and is dedicated to the managerial implications on reducing risks of processing problems.展开更多
Perilla frutescens(Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have ...Perilla frutescens(Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens(EOPF) attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress(CUMS)-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF(3, 6, and 9 mg·kg-1) and a positive control drug fluoxetine(20 mg·kg-1) were administered through gastric intubation to mice once daily for three consecutive weeks from the 3rd week. Open-field test, sucrose consumption test, tail suspension test(TST), and forced swimming test(FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine(5-HT) and its metabolite, 5-hydroxyindoleacetic acid(5-HIAA), in mouse hippocampus were determined by HPLC–ECD. Serum interleukin(IL)-1, IL-6, and tumor necrosis factor(TNF)-α levels were evaluated by enzyme-linked immunosorbent assay(ELISA). The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1β, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1β, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between alteration of serotonergic responses and anti-inflammatory effects.展开更多
The depression-like behavior phenotype,neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy.The pre...The depression-like behavior phenotype,neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy.The present study aimed to clarify the dynamic changes of depression-like behavior,dentate gyrus neurogenesis and hippocampal miR-124 expression during depression induced by chronic stress to reveal pathological features at different stages of depression and to further provide insight into depression treatment.Chronic unpredictable mild stress depression models were established by exposing Sprague-Dawley rats to various mild stressors,including white noise,thermal swimming,stroboscopic illumination,soiled cages,pairing with three other stressed animals,cold swimming,tail pinch,restraint and water and food deprivation.Chronic unpredictable mild stress model rats underwent dynamic observation from 1 to 8 weeks and were compared with a control group(normal feeding without any stressors).To observe changes in the depression-like behavior phenotype during chronic unpredictable mild stress-induced depression,a sucrose preference test was used to evaluate the degree of anhedonia.An open-field test was used to evaluate locomotor activity and anxiety status.Compared with the control group,chronic unpredictable mild stress rats lost weight but did not have a depression-like behavioral phenotype at 1-4 weeks.Chronic unpredictable mild stress rats presented decreased sucrose preference and locomotor activity at 5-8 weeks.In addition,chronic unpredictable mild stress rats did not have significant anxiety-like behavior during 1-8 weeks of modeling.To observe neurogenesis dysfunctions and changes in neuronal number in the dentate gyrus during chronic unpredictable mild stress-induced depression,markers(DCX and DCX/BrdU)of neural proliferation and differentiation and the neuronal marker NeuN were assessed by immunofluorescence.Compared with the control group,neurogenesis and the neuronal number in the dentate gyrus did not change from 2 to 6 weeks;however,neural proliferation and differentiation in the dentate gyrus decreased,and the number of neurons decreased until the eighth week in the chronic unpredictable mild stress group.Real-time quantitative reverse transcription polymerase chain reaction assays and fluorescence in situ hybridization were used to measure the expression of hippocampal miR-124 during chronic unpredictable mild stress-induced depression.The results showed that the expression of hippocampal miR-124 was unchanged during the first 4 weeks but increased from 5 to 6 weeks and decreased from 7 to 8 weeks compared with the control group.These findings indicate that during chronic unpredictable mild stress-induced depression,the behavioral phenotype,miR-124 expression in the hippocampus,neurogenesis in the dentate gyrus and neuronal numbers showed dynamic changes,which suggested that various pathological changes occur at different stages of depression.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2015.展开更多
Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor （BDNF）. In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of po...Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor （BDNF）. In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippo- campus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.展开更多
Icariin(ICA) has a significant capacity to protect against depression and hippocampal injury,but it cannot effectively cross the bloodbrain barrier and accumulate in the brain.Therefore,the mechanism by which ICA prot...Icariin(ICA) has a significant capacity to protect against depression and hippocampal injury,but it cannot effectively cross the bloodbrain barrier and accumulate in the brain.Therefore,the mechanism by which ICA protects against hippocampal injury in depression remains unclear.In this study,we performed proteomics analysis of cerebrospinal fluid to investigate the mechanism by which ICA prevents dysfunctional hippocampal neurogenesis in depression.A rat model of depression was established through exposure to chronic unpredictable mild stress for 6 weeks,after which 120 mg/kg ICA was administered subcutaneously every day.The results showed that ICA alleviated depressive symptoms,learning and memory dysfunction,dysfunctional neurogenesis,and neuronal loss in the dentate gyrus of rats with depression.Neural stem cells from rat embryonic hippocampi were cultured in media containing 20% cerebrospinal fluid from each group of rats and then treated with 100 μM corticosterone.The addition of cerebrospinal fluid from rats treated with ICA largely prevented the corticosterone-mediated inhibition of neuronal proliferation and differentiation.Fifty-two differentially expressed proteins regulated by chronic unpredictable mild stress and ICA were identified through proteomics analysis of cerebrospinal fluid.These proteins were mainly involved in the ribosome,PI3 K-Akt signaling,and interleukin-17 signaling pathways.Parallel reaction monitoring mass spectrometry showed that Rps4 x,Rps12,Rps14,Rps19,Hsp90 b1,and Hsp90 aa1 were up-regulated by chronic unpredictable mild stress and down-regulated by ICA.In contrast,Htr A1 was down-regulated by chronic unpredictable mild stress and up-regulated by ICA.These findings suggest that ICA can prevent depression and dysfunctional hippocampal neurogenesis through regulating the expression of certain proteins found in the cerebrospinal fluid.The study was approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2017.展开更多
Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In th...Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results conifrmed that depressive symptoms lessened after treatment with high-dose （150 mg/kg） Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule signiifcantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effec-tively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain.展开更多
OBJECTIVE: To evaluate the effect of compound Gaoziban tablet(复方高滋斑片, CGZBT) on depression, and to investigate the underlying mechanism. METHODS: The components of CGZBT were analysed by high-performance liquid ...OBJECTIVE: To evaluate the effect of compound Gaoziban tablet(复方高滋斑片, CGZBT) on depression, and to investigate the underlying mechanism. METHODS: The components of CGZBT were analysed by high-performance liquid chromatography. Then, we assessed the effects of varying doses of CGZBT on an established chronic unpredictable mild stress(CUMS) model in rats. Whether animals were depressed was evaluated by sucrose preference test, open field test and forced swimming test. Neurotransmitters of hippocampus were detected by liquid chromatography-mass spectrometry. Serum levels of tumor necrosis factor-alpha(TNF-α), interleukin(IL)-1β, IL-6, IL-4, and IL-10 were measured by enzyme-linked immunosorbent assay. Expressions of toll-like receptor 4(TLR4), myeloid differentiation factor 88(My D88), phospho-nuclear factorkappa B(p-NF-κB), cyclooxygenase-2(COX-2), ionized calcium binding adapter molecule-1(IBA-1) were assessed by immunohistochemical staining and western blotting. RESULTS: Eight compounds were identified from CGZBT, moreover, our results showed that CGZBT effectively reversed the CUMS-induced decrease in sucrose preference, shortened the movement distance and prolonged immobility time. CGZBT significantly increased levels of 5-hydroxytryptamine, dopamine, norepinephrine, 5-hydroxyindoleacetic acid levels, and reduced the expression of TNF-α, IL-1β, IL-6, yet increased IL-4 and IL-10. Furthermore, the expressions of TLR4, My D88, COX-2, p-NF-κB and IBA-1 in hippocampus were effectively reversed after treatment with CGZBT. CONCLUSIONS: These results indicated that CGZBT could, at least in part, alleviate depression induced by CUMS via the TLR4/My D88/NF-κB pathway, suggesting its potential as an antidepressant drug.展开更多
Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous...Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.展开更多
Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity.The overall prevalence of geriatric depression with clinically significant symptoms is curre...Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity.The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise.Recent studies have demonstrated that altered expressions of long non-coding RNAs(lncRNAs)in the brain affect neurodevelopment and manifest modulating functions during the depression.However,most lncRNAs have not yet been studied.Herein,we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors,as well as their corresponding response following antidepressant fluoxetine treatment.A chronic unpredictable mild stress(CUMS)mouse model was applied.A sixweek fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors.In addition,differential expression analysis of lncRNAs was performed following RNA-sequencing.A total of 282 lncRNAs(134 up-regulated and 148 down-regulated)were differentially expressed in CUMS-induced mice relative to non-stressed counterparts(P<0.05).Moreover,370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention.Gene Ontology(GO)analyses showed an association between significantly dysregulated lncRNAs and protein binding,oxygen binding,and transport activity,while the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways.Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus.The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.展开更多
The spleen is critical for immunity.It is the largest immune organ and immune center in the peripheral system.While the relationship between behavior and immunity has been demonstrated in physiology and diseases,the r...The spleen is critical for immunity.It is the largest immune organ and immune center in the peripheral system.While the relationship between behavior and immunity has been demonstrated in physiology and diseases,the role of the spleen in behavior is not clear.To investigate the effects of the spleen on behaviors,we performed a refined splenectomy procedure on C57BL/6J mice and performed an open field test,circadian rhythm test,elevated plus maze,sucrose preference test,and Barnes maze test.Splenectomy did not induce changes in general locomotion,circadian rhythms,learning and memory,or depression/anxiety-related behaviors.To further investigate the effects of spleen on stress susceptibility,we established mouse models of depression through chronic unpredictable mild stress.The behavioral performances of mice subjected to splenectomy showed no differences from control animals.These findings suggest that splenectomy does not cause changes in baseline behavioral performance in mice.展开更多
Background:The chronic unpredictable mild stress(CUMS)model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression.However,there are no widely recognised standard...Background:The chronic unpredictable mild stress(CUMS)model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression.However,there are no widely recognised standards for strategies for modeling and for behavioral testing.The present study aimed to optimize the protocols for food deprivation and the sucrose preference test(SPT)for the CUMS model.Methods:We first evaluated the effects of different long periods of food deprivation on the body weight of Sprague Dawley(SD)rats by testing food deprivation for 24 hours(8:00-8:00^+),food deprivation for 12 hours during the daytime(8:00-20:00)and food deprivation for 12 hours at night(20:00-8:00^+).Next,we established a SD rat CUMS model with 15 different stimulations,and used body weight measurement,SPT,forced swim test(FST),open field test(OFT)and Morris water maze(MWM)test to verify the success of the modeling.In the SPT,consumption of sucrose and pure water within 1 and 12 hours was measured.Results:Twelve hours of food deprivation during the daytime(8:00-20:00)had no effect on body weight,while 12 hours of food deprivation at night(20:00-8:00^+)and 24 hours of food deprivation(8:00-8:00^+)significantly reduced the mean body weight of the SD rats.When SPT was used to verify the successful establishment of the CUMS rat model,sucrose consumption measured within 12 hours was less variable than that measured within 1 hour.Conclusions:Twelve hours of food deprivation in the daytime(8:00-20:00)may be considered a mild stimulus for the establishment of a CUMS rat model.Measuring sucrose consumption over 12 hours is recommended for SPT.展开更多
文摘Background:Machine learning to predict morbidity and mortality-especially in a population traditionally considered low risk-has not been previously examined.We sought to characterize the incidence of death among patients with a low estimated morbidity and mortality risk based on the National Surgical Quality Improvement Program(NSQIP)estimated probability(EP),as well as develop a machine learning model to identify individuals at risk for“unpredicted death”(UD)among patients undergoing hepatopancreatic(HP)procedures.Methods:The NSQIP database was used to identify patients who underwent elective HP surgery between 2012-2017.The risk of morbidity and mortality was stratified into three tiers(low,intermediate,or high estimated)using a k-means clustering method with bin sorting.A machine learning classification tree and multivariable regression analyses were used to predict 30-day mortality with a 10-fold cross validation.C statistics were used to compare model performance.Results:Among 63,507 patients who underwent an HP procedure,median patient age was 63(IQR:54-71)years.Patients underwent either pancreatectomy(n=38,209,60.2%)or hepatic resection(n=25,298,39.8%).Patients were stratified into three tiers of predicted morbidity and mortality risk based on the NSQIP EP:low(n=36,923,58.1%),intermediate(n=23,609,37.2%)and high risk(n=2,975,4.7%).Among 36,923 patients with low estimated risk of morbidity and mortality,237 patients(0.6%)experienced a UD.According to the classification tree analysis,age was the most important factor to predict UD(importance 16.9)followed by preoperative albumin level(importance:10.8),disseminated cancer(importance:6.5),preoperative platelet count(importance:6.5),and sex(importance 5.9).Among patients deemed to be low risk,the c-statistic for the machine learning derived prediction model was 0.807 compared with an AUC of only 0.662 for the NSQIP EP.Conclusions:A prognostic model derived using machine learning methodology performed better than the NSQIP EP in predicting 30-day UD among low risk patients undergoing HP surgery.
基金supported by the National Natural Science Foundation of China(Grant Nos.U2342210 and 42275043)the National Institute of Natural Hazards,Ministry of Emergency Management of China(Grant Nos.J2223806,ZDJ2024-25 and ZDJ2025-34)。
文摘Climate models are essential for understanding past,present,and future changes in atmospheric circulation,with circulation modes providing key sources of seasonal predictability and prediction uncertainties for both global and regional climates.This study assesses the performance of models participating in phase 6 of the Coupled Model Intercomparison Project in simulating interannual variability modes of Northern Hemisphere 500-hPa geopotential height during winter and summer,distinguishing predictable(potentially predictable on seasonal or longer timescales)and unpredictable(intraseasonal and essentially unpredictable at long range)components,using reanalysis data and a variance decomposition method.Although most models effectively capture unpredictable modes in reanalysis,their ability to reproduce dominant predictable modes-specifically the Pacific-North American pattern,Arctic Oscillation,and Western Pacific Oscillation in winter,and the East Atlantic and North Atlantic Oscillations in summer-varies notably.An optimal ensemble is identified to distinguish(a)predictable-external modes,dominated by external forcing,and(b)predictable-internal modes,associated with slow internal variability,during the historical period(1950-2014)and the SSP5-8.5 scenario(2036-2100).Under increased radiative forcing,the leading winter/summer predictable-external mode exhibits a more uniform spatial distribution,remarkably larger trend and annual variance,and enhanced height-sea surface temperature(SST)covariance under SSP5-8.5 compared to historical conditions.The dominant winter/summer predictable-internal modes also exhibit increased variance and height-SST covariance under SSP5-8.5,along with localized changes in spatial configuration.Minimal changes are observed in spatial distribution or variance for dominant winter/summer unpredictable modes under SSP5-8.5.This study,from a predictive perspective,deepens our understanding of model uncertainties and projected changes in circulations.
文摘“As a global citizen,I speak to you with fear.I fear increasing unpredictability and fragmentation that can easily result in conflict.And in conflict,no one wins-we all lose,”Matias Acosta,CEO of Italian cleantech firm Cosysense,told the audience at the China Today•Macao Salon dialogue in Hengqin,south China’s Guangdong Province,on July 27,2025.
基金funded by the National Research, Development and Innovation Office, Hungary (OTKA K139021 to AZL and LC)A Stipendium Hungaricum Scholarship and dissertation scholarship from Tempus Public Foundation
文摘Under natural conditions, organisms regularly experience seasonal or unpredictable fluctuations in their diet that may shape the quantity and quality of their reproduction. While these dietary shifts are known to influence overall reproductive output, their specific effects on the proportional composition of egg components remain unexplored. To partially simulate the natural conditions, we conducted two trials using adult Japanese Quails (Coturnix japonica) to examine how dietary restriction and unpredictable feeding influence the proportional composition of egg components. In the first trial, quails were assigned to one of four treatments: full-fed (control) or restricted feeding at 20% (DR20), 30% (DR30), and 40% (DR40) below daily intake. In the second trial, quails were assigned to one of three treatments: full feeding (control), constant 40% restriction (DR40), or unpredictable feeding schedule (UNPR). Each trial lasted for 14 days, and birds were housed individually. Severe dietary restrictions (DR30, DR40) reduced albumen and shell mass, shell thickness, and egg volume. However, yolk mass, yolk color, egg shape index, and shell density remained unaffected across all dietary levels. Severe restrictions also increased the yolk ratio while reducing the albumen ratio, suggesting that birds may evolutionarily prioritize yolk deposition to sustain reproductive functions. However, reduced albumen content due to maternal nutritional stress may also limit essential nutrients, and disrupt the embryo's osmoregulation, which ultimately affects offspring quality. Reduced shell contents at the severe restriction levels can affect the egg's ability to provide physical protection, regulate gas exchange and control water loss, thereby influencing embryonic development. In contrast, moderate restriction (DR20) and unpredictable feeding (UNPR) had no effect on any of the egg traits. These findings suggest that quails strategically allocate resources among egg components under dietary constraints, indicating potential trade-offs in reproductive investment. The resilience observed under moderate restriction and unpredictability underscores the species' adaptive capacity in fluctuating environments.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2020A1515110608)Department of Education of Guangdong Province-Guangdong Province General University Youth Innovative Talent Project(2019KQNCX039).
文摘Background:Childhood environmental unpredictability(CEU)is crucial to personal development,profoundly influence physical and psychological growth particularly,and psychopathy is recognized as a dark personality trait.The aim of this study is to investigate the effects of insecure attachment and life history strategy(LHS)on the relationship between CEU and psychopathy by establishing a sequential mediation model based on evolutionary life history theory and cognitive-affective personality system.Methods:A group of 532 undergraduates completed the measurements for CEU,insecure attachment,LHS,and psychopathy,and Bootstrap mediation test through SPSS 25.0 and PROCESS macro tool was used to examine the relationship among these variables.Results:The results revealed positive relations between CEU and insecure attachment(β=0.87,p<0.001),CEU and LHS(β=0.11,p<0.001),and CEU and psychopathy(β=0.14,p<0.001).Insecure attachment was also positively associated with LHS(β=0.62,p<0.001)and psychopathy(β=0.04,p<0.001).In addition,LHS was significantly associated with psychopathy(β=0.08,p<0.001).The relationship between CEU and psychopathy is mediated independently and sequentially by insecure attachment and LHS.Conclusion:The current research shows the relationship between CEU and psychopathy,as well as the mechanism of insecure attachment and life history strategy as mediators.
基金supported by the Traditional Chinese Medicine Intervention of Metabolic Diseases Research Project(90020165120003)the Key Laboratory of Health Cultivation of the Ministry of Education(2024-JYB-KYPT-002).
文摘Objective:To evaluate the effects of Wuhua herbal tea on chronic unpredictable mild stress(CUMS)-induced depression and explore its mechanism of action in combating depression.Methods:We tested the antidepressant effects of Wuhua herbal tea in a rat model of CUMS-induced depression using fluoxetine as a positive control.The rats were divided into four groups:control group,model group,fluoxetine group,and Wuhua herbal tea group.The rats underwent body weight measurements,sucrose preference test,and open-field test.Enzyme-linked immunosorbent assay kits were used to detect the serum levels of serotonin,dopamine,adrenocorticotropic hormone(ACTH),corticosterone,norepinephrine,and interleukin-6.Intergroup comparisons and detection of brain-derived neurotrophic factor(BDNF),cAMP-response element binding protein(CREB),Janus kinase 2(JAK2),and signal transducer and activator of transcription 3(STAT3)mRNA expression in the hippocampus were performed using RTPCR.Immunohistochemistry was used to identify the expression of phosphorylated JAK2(p-JAK2)and phosphorylated STAT3(p-STAT3)proteins in hippocampal paraffin sections of CUMS rats.Results:Compared with the control group,the model group rats had depressive tendencies,exhibiting low vitality and interest in various behavioral indicators which were signs of despair.The Wuhua herbal tea group statistically increased the levels of serotonin and dopamine in the serum of CUMS rats to varying degrees(P=.015 and P=.002);reduced serum levels of ACTH,corticosterone,norepinephrine,and interleukin-6(all P<.05);and decreased mRNA expression of BDNF,CREB,JAK2,and STAT3 in the hippocampus(all P<.05);and decreased p-STAT3 protein levels(P=.006).Conclusion:Wuhua herbal tea shows antidepressant potential in CUMS rats by modulating the HPA axis and inhibiting JAK2-STAT3 overactivation,alleviating neuroinflammation.It also restores BDNF-CREB pathway function,reducing depressive symptoms.
基金supported by the National Natural Science Foundation of China(No 82305144)the Jiangsu Provincial Natural Science Foundation Project for Universities(No 23KJB360004)the National Natural Science Foundation Supporting Project of Nanjing University of Chinese Medicine(No XPT82305144).
文摘Background Major depressive disorder(MDD),characterised by persistent anhedonia and elevated suicide risk,represents a global mental health challenge.Recent studies suggest a link between gut-brain axis dysfunction and depression.The natural compound paeoniflorin demonstrates clinically relevant antidepressant effects,yet its underlying neurobiological mechanisms remain elusive.Aims This study aims to examine how paeoniflorin alleviates depression-like behaviours in rats subjected to chronic unpredictable mild stress(CUMS)by modulating the function of gut-brain axis,and explore the connections between gut microbiota,metabolites and MDD.Methods Depression-like behaviours in rats were induced by CUMS,and the antidepressant effect of paeoniflorin was assessed using behavioural tests.The composition and function of the intestinal microbiota were analysed using 16S rRNA sequencing,and metabolomic analysis was performed on serum,hippocampus,jejunum and faecal samples.Enzyme-linked immunosorbent assay and hematoxylin and eosin staining were used to detect the levels of inflammatory factors and cortisol,as well as the infiltration of inflammatory cells in the jejunum of rats after cohousing.Long-term potentiation assays and Golgi staining were used to detect dendritic spine density and synaptic plasticity,respectively.Results Paeoniflorin significantly alleviated depression-like behaviours and cognitive deficits in CUMS rats.16S rRNA sequencing revealed that paeoniflorin improved the abundance and diversity of the gut microbiota in CUMS rats.Enrichment of differential metabolites in the brain,intestine,faeces and serum revealed a primary accumulation in the amino acid metabolism pathway.We further observed a correlation between the relative abundance of microbial communities and metabolites.Cohousing experiments verified that microbial metabolites of paeoniflorin can reduce neuroinflammation and improve synaptic plasticity.Conclusions Disruptions in gut microbiota and its metabolites impair gut-brain interactions.Paeoniflorin’s neuroprotective and antidepressant effects are mediated through the modulation of the function of the gut-brain axis.
文摘Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to stressors.In the present study,the effect of chronic unpredictable mild stress（CUMS）on CRH neurons was investigated in rat brain.Methods The rats were exposed to one of the stressors each day for 21 d.Immunostaining was performed to detect the CRH-positive neurons in the paraventricular nucleus（PVN）of the hypothalamus and in amygdala.Results After the stress protocol,the animals showed a reduction in body weight gain as well as reduced sucrose preference and locomotor activity.Interestingly,the CRH neurons in both PVN and central nucleus of the amygdala（CeA）were stimulated by CUMS.The densities of CRH-containing neurons in both PVN and CeA were significantly higher than those in control group.Conclusion The CRH systems in PVN and CeA may both contribute to depression-like behaviors during CUMS.
基金supported by the National Natural Science Foundation of China(7117111271502073)。
文摘This paper analyzes a problem processing mechanism in a new collaboration system between the main manufacturer and the supplier in the"main manufacturer-supplier"mode,which has been widely applied in the collaborative development management of the complex product.This paper adopts the collaboration theory,the evolutionary game theory and numerical simulation to analyze the decision-making mechanism where one upstream supplier and one downstream manufacturer must process an unpredicted problem without any advance contract in common.Results show that both players'decision-makings are in some correlation with the initial state,income impact coefficients,and dealing cost.It is worth noting that only the initial state influences the final decision,while income impact coefficients and dealing cost just influence the decision process.This paper shows reasonable and practical suggestions for the manufacturer and supplier in a new collaboration system for the first time and is dedicated to the managerial implications on reducing risks of processing problems.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Natural Science Foundation of Jiangsu Province of China(No.BK2011630)
文摘Perilla frutescens(Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens(EOPF) attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress(CUMS)-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF(3, 6, and 9 mg·kg-1) and a positive control drug fluoxetine(20 mg·kg-1) were administered through gastric intubation to mice once daily for three consecutive weeks from the 3rd week. Open-field test, sucrose consumption test, tail suspension test(TST), and forced swimming test(FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine(5-HT) and its metabolite, 5-hydroxyindoleacetic acid(5-HIAA), in mouse hippocampus were determined by HPLC–ECD. Serum interleukin(IL)-1, IL-6, and tumor necrosis factor(TNF)-α levels were evaluated by enzyme-linked immunosorbent assay(ELISA). The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1β, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1β, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between alteration of serotonergic responses and anti-inflammatory effects.
基金supported by the National Natural Science Foundation of China,No.81573858(to LLW)the Natural Science Foundation of Guangdong Province of China,No.2016A030313648(to CY)the Major Basic Research Project of Educational Commission of Guangdong Province of China,No.2017KZDXM020(to CY)
文摘The depression-like behavior phenotype,neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy.The present study aimed to clarify the dynamic changes of depression-like behavior,dentate gyrus neurogenesis and hippocampal miR-124 expression during depression induced by chronic stress to reveal pathological features at different stages of depression and to further provide insight into depression treatment.Chronic unpredictable mild stress depression models were established by exposing Sprague-Dawley rats to various mild stressors,including white noise,thermal swimming,stroboscopic illumination,soiled cages,pairing with three other stressed animals,cold swimming,tail pinch,restraint and water and food deprivation.Chronic unpredictable mild stress model rats underwent dynamic observation from 1 to 8 weeks and were compared with a control group(normal feeding without any stressors).To observe changes in the depression-like behavior phenotype during chronic unpredictable mild stress-induced depression,a sucrose preference test was used to evaluate the degree of anhedonia.An open-field test was used to evaluate locomotor activity and anxiety status.Compared with the control group,chronic unpredictable mild stress rats lost weight but did not have a depression-like behavioral phenotype at 1-4 weeks.Chronic unpredictable mild stress rats presented decreased sucrose preference and locomotor activity at 5-8 weeks.In addition,chronic unpredictable mild stress rats did not have significant anxiety-like behavior during 1-8 weeks of modeling.To observe neurogenesis dysfunctions and changes in neuronal number in the dentate gyrus during chronic unpredictable mild stress-induced depression,markers(DCX and DCX/BrdU)of neural proliferation and differentiation and the neuronal marker NeuN were assessed by immunofluorescence.Compared with the control group,neurogenesis and the neuronal number in the dentate gyrus did not change from 2 to 6 weeks;however,neural proliferation and differentiation in the dentate gyrus decreased,and the number of neurons decreased until the eighth week in the chronic unpredictable mild stress group.Real-time quantitative reverse transcription polymerase chain reaction assays and fluorescence in situ hybridization were used to measure the expression of hippocampal miR-124 during chronic unpredictable mild stress-induced depression.The results showed that the expression of hippocampal miR-124 was unchanged during the first 4 weeks but increased from 5 to 6 weeks and decreased from 7 to 8 weeks compared with the control group.These findings indicate that during chronic unpredictable mild stress-induced depression,the behavioral phenotype,miR-124 expression in the hippocampus,neurogenesis in the dentate gyrus and neuronal numbers showed dynamic changes,which suggested that various pathological changes occur at different stages of depression.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2015.
基金supported by a grant from the Experimental Animal Science and Technology Project of Zhejiang Province in China,No.2012C37083
文摘Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor （BDNF）. In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippo- campus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.
基金supported by the National Natural Science Foundation of China,No.81774102 (to LLW)。
文摘Icariin(ICA) has a significant capacity to protect against depression and hippocampal injury,but it cannot effectively cross the bloodbrain barrier and accumulate in the brain.Therefore,the mechanism by which ICA protects against hippocampal injury in depression remains unclear.In this study,we performed proteomics analysis of cerebrospinal fluid to investigate the mechanism by which ICA prevents dysfunctional hippocampal neurogenesis in depression.A rat model of depression was established through exposure to chronic unpredictable mild stress for 6 weeks,after which 120 mg/kg ICA was administered subcutaneously every day.The results showed that ICA alleviated depressive symptoms,learning and memory dysfunction,dysfunctional neurogenesis,and neuronal loss in the dentate gyrus of rats with depression.Neural stem cells from rat embryonic hippocampi were cultured in media containing 20% cerebrospinal fluid from each group of rats and then treated with 100 μM corticosterone.The addition of cerebrospinal fluid from rats treated with ICA largely prevented the corticosterone-mediated inhibition of neuronal proliferation and differentiation.Fifty-two differentially expressed proteins regulated by chronic unpredictable mild stress and ICA were identified through proteomics analysis of cerebrospinal fluid.These proteins were mainly involved in the ribosome,PI3 K-Akt signaling,and interleukin-17 signaling pathways.Parallel reaction monitoring mass spectrometry showed that Rps4 x,Rps12,Rps14,Rps19,Hsp90 b1,and Hsp90 aa1 were up-regulated by chronic unpredictable mild stress and down-regulated by ICA.In contrast,Htr A1 was down-regulated by chronic unpredictable mild stress and up-regulated by ICA.These findings suggest that ICA can prevent depression and dysfunctional hippocampal neurogenesis through regulating the expression of certain proteins found in the cerebrospinal fluid.The study was approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2017.
基金supported by the National Natural Science Foundation of China,No.81071093,81171268
文摘Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results conifrmed that depressive symptoms lessened after treatment with high-dose （150 mg/kg） Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule signiifcantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effec-tively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain.
基金Supported by the Scientific Research Project of Education Department of Hubei Province (D20192003):Synthesis and Anti-hepatocellular Carcinoma Effect of Novel NMT1 Inhibitors。
文摘OBJECTIVE: To evaluate the effect of compound Gaoziban tablet(复方高滋斑片, CGZBT) on depression, and to investigate the underlying mechanism. METHODS: The components of CGZBT were analysed by high-performance liquid chromatography. Then, we assessed the effects of varying doses of CGZBT on an established chronic unpredictable mild stress(CUMS) model in rats. Whether animals were depressed was evaluated by sucrose preference test, open field test and forced swimming test. Neurotransmitters of hippocampus were detected by liquid chromatography-mass spectrometry. Serum levels of tumor necrosis factor-alpha(TNF-α), interleukin(IL)-1β, IL-6, IL-4, and IL-10 were measured by enzyme-linked immunosorbent assay. Expressions of toll-like receptor 4(TLR4), myeloid differentiation factor 88(My D88), phospho-nuclear factorkappa B(p-NF-κB), cyclooxygenase-2(COX-2), ionized calcium binding adapter molecule-1(IBA-1) were assessed by immunohistochemical staining and western blotting. RESULTS: Eight compounds were identified from CGZBT, moreover, our results showed that CGZBT effectively reversed the CUMS-induced decrease in sucrose preference, shortened the movement distance and prolonged immobility time. CGZBT significantly increased levels of 5-hydroxytryptamine, dopamine, norepinephrine, 5-hydroxyindoleacetic acid levels, and reduced the expression of TNF-α, IL-1β, IL-6, yet increased IL-4 and IL-10. Furthermore, the expressions of TLR4, My D88, COX-2, p-NF-κB and IBA-1 in hippocampus were effectively reversed after treatment with CGZBT. CONCLUSIONS: These results indicated that CGZBT could, at least in part, alleviate depression induced by CUMS via the TLR4/My D88/NF-κB pathway, suggesting its potential as an antidepressant drug.
基金supported by the National Natural Science Foundation of China,No.30370537
文摘Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.
基金This work was supported by the Scientific Research Projects of Universities in Inner Mongolia Autonomous Region(NJZY111)Natural Scientific Research Projects of Inner Mongolia Autonomous Region(2020MS03060)We thank Elsevier Ltd.,UK and FreeScience,China for their assistance in English editing of the manuscript.
文摘Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity.The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise.Recent studies have demonstrated that altered expressions of long non-coding RNAs(lncRNAs)in the brain affect neurodevelopment and manifest modulating functions during the depression.However,most lncRNAs have not yet been studied.Herein,we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors,as well as their corresponding response following antidepressant fluoxetine treatment.A chronic unpredictable mild stress(CUMS)mouse model was applied.A sixweek fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors.In addition,differential expression analysis of lncRNAs was performed following RNA-sequencing.A total of 282 lncRNAs(134 up-regulated and 148 down-regulated)were differentially expressed in CUMS-induced mice relative to non-stressed counterparts(P<0.05).Moreover,370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention.Gene Ontology(GO)analyses showed an association between significantly dysregulated lncRNAs and protein binding,oxygen binding,and transport activity,while the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways.Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus.The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.
基金supported by the National Natural Science Foundation of China,Nos.81772438,81974357the Guangzhou Municipal Science and Technology Program,No.202206010197(all to YL)。
文摘The spleen is critical for immunity.It is the largest immune organ and immune center in the peripheral system.While the relationship between behavior and immunity has been demonstrated in physiology and diseases,the role of the spleen in behavior is not clear.To investigate the effects of the spleen on behaviors,we performed a refined splenectomy procedure on C57BL/6J mice and performed an open field test,circadian rhythm test,elevated plus maze,sucrose preference test,and Barnes maze test.Splenectomy did not induce changes in general locomotion,circadian rhythms,learning and memory,or depression/anxiety-related behaviors.To further investigate the effects of spleen on stress susceptibility,we established mouse models of depression through chronic unpredictable mild stress.The behavioral performances of mice subjected to splenectomy showed no differences from control animals.These findings suggest that splenectomy does not cause changes in baseline behavioral performance in mice.
基金This work was supported by Social livelihood projects of Chongqing Science and Technology Bureau(cstc2017shms-zdyfX0048,csts2017shmsA00007).
文摘Background:The chronic unpredictable mild stress(CUMS)model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression.However,there are no widely recognised standards for strategies for modeling and for behavioral testing.The present study aimed to optimize the protocols for food deprivation and the sucrose preference test(SPT)for the CUMS model.Methods:We first evaluated the effects of different long periods of food deprivation on the body weight of Sprague Dawley(SD)rats by testing food deprivation for 24 hours(8:00-8:00^+),food deprivation for 12 hours during the daytime(8:00-20:00)and food deprivation for 12 hours at night(20:00-8:00^+).Next,we established a SD rat CUMS model with 15 different stimulations,and used body weight measurement,SPT,forced swim test(FST),open field test(OFT)and Morris water maze(MWM)test to verify the success of the modeling.In the SPT,consumption of sucrose and pure water within 1 and 12 hours was measured.Results:Twelve hours of food deprivation during the daytime(8:00-20:00)had no effect on body weight,while 12 hours of food deprivation at night(20:00-8:00^+)and 24 hours of food deprivation(8:00-8:00^+)significantly reduced the mean body weight of the SD rats.When SPT was used to verify the successful establishment of the CUMS rat model,sucrose consumption measured within 12 hours was less variable than that measured within 1 hour.Conclusions:Twelve hours of food deprivation in the daytime(8:00-20:00)may be considered a mild stimulus for the establishment of a CUMS rat model.Measuring sucrose consumption over 12 hours is recommended for SPT.
