Antidepressant effects of Yuanzhi (Polygalae Radix) extract on chronic unpredictable mild stress-induced depression in rats: modulation of the NLRP3 inflammasome and NF-κB pathway

Objective To investigate the antidepressant effects of Yuanzhi(Polygalae Radix;PR)aqueous extract on chronic unpredictable mild stress(CUMS)-induced depression rat models and the underlying mechanisms.Methods A total of 40 male Sprague Dawley(SD)rats were randomly divided into control;model;low dose of PR(PR-L;0.5 g/kg);high dose of PR(PR-H;1 g/kg);and fluoxetine(10 mg/kg)groups;with 8 rats in each group.Except for the rats in control group;those in the other four groups underwent CUMS-induced depression modeling.PR and fluoxetine were administered intragastrically once daily;30 min prior to the CUMS procedure;for 14 consecu-tive days until the behavioral tests were performed.After CUMS modeling;the sucrose prefer-ence test(SPT);open field test(OFT);novelty-suppressed feeding test(NSFT);forced swim test(FST);and tail suspension test(TST)were employed to assess the pharmacological ef-fects of PR on the mitigation of depressive-like behaviors in rat models.Additionally;the en-zyme-linked immunosorbent assay(ELISA)was utilized to quantify the serum levels of tumor necrosis factor(TNF)-α;interleukin(IL)-6;and IL-1βin the rats.Western blot analysis was al-so conducted to evaluate the protein expression levels of nuclear factor kappa-B(NF-κB);in-ducible nitric oxide synthase(iNOS);cyclooxygenase-2(COX-2);nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain containing 3(NLRP3);apoptosis-associated speck-like protein containing caspase recruitment domain(ASC);and caspase-1 in the hippocampal tissues of the rats.Immunofluorescence staining was per-formed to observe the morphological changes in ionized calcium-binding adapter molecule 1 positive(Iba-1+)cells in the dentate gyrus(DG)of rats with CUMS-induced depression.Results(i)Treatment with PR-H and fluoxetine resulted in significant enhancements in both the total distance and time the rats moved during tests(P<0.01 and P<0.05;respectively).Post-administration of PR-H and fluoxetine also led to statistically significant increase in su-crose preference among rats(P<0.05).Besides;PR-L;PR-H;and fluoxetine treatment markedly decreased the latency of ingestion(P<0.05;P<0.05;and P<0.01;respectively).As observed from the FST;PR-L;PR-H;and fluoxetine presented antidepressant effects on rats with CUMS-induced depression;leading to the reduction in time of their immobility(P<0.05;P<0.01;and P<0.01;respectively).The results of TST indicated reduced immobility time in rats receiving PR-H and fluoxetine treatment as well(P<0.01).(ii)Rats in model group showed an increase in the levels of Iba-1+microglia in their left and right brains in compari-son with control group(P<0.01).However;such increase was negated post PR treatment(P<0.01).Treatment with PR-L;PR-H;and fluoxetine considerably reduced the levels of inflam-matory factors(TNF-α;IL-1β;and IL-6;P<0.01).In addition;treatment of PR-L and PR-H ef-fectively counteracted the elevated levels of NLRP3;ASC;and caspase-1;and markedly down-regulated the expression levels of phosphorylated p65(p-p65);COX-2;and iNOS in rats’hip-pocampus(P<0.01).Conclusion Collectively;these findings indicate that PR exerts an antidepressant effect on rats with CUMS-induced depression partially through the modulation of the NLRP3 and NF-κB signaling pathways.

Octreotide ameliorates gastric lesions in chronically mild stressed rats

AIM:To evaluate the effect of chronic mild stress(CMS) on the emergence of gastric ulcers and possible modulation by octreotide,a synthetic somatostatin analogue. METHODS:Adult male Wistar rats were subjected to nine different unpredictable random stress procedures for 21 d,a multifactorial interactional animal model for CMS.Octreotide was administered daily for 21 d at two dose levels(50 and 90μg/kg)before exposure to stress procedure.Macro-and microscopical assessments were made,in addition to quantification of plasma corticosterone and gastric mucosal inflammatory,oxidative stress, and apoptotic biomarkers. RESULTS:Exposure to CMS elevated plasma corticosterone(28.3±0.6μg/dL,P=0.002),an event that was accompanied by gastric lesions(6.4±0.16 mm,P=0.01) and confirmed histopathologically.Moreover,the insult elevated gastric mucosal lipid peroxides(13±0.5 nmol/g tissue,P=0.001),tumor necrosis factor-α(3008.6±78.18 pg/g tissue,P<0.001),prostaglandin E2(117.1 ±4.31 pg/g tissue,P=0.002),and caspase-3 activity (2.4±0.14 OD/mg protein,P=0.002).Conversely,CMS mitigated interleukin-10(627.9±12.82 pg/g tissue,P= 0.001).Furthermore,in animals exposed to CMS,octreotide restored plasma corticosterone(61%and 71%from CMS,P=0.002)at both dose levels.These beneficial effects were associated with a remarkable suppression of gastric lesions(38%and 9%from CMS,P=0.01)and reversal of derangements in gastric mucosa. CONCLUSION:The current investigation provides evidence that exposure to CMS induces gastric ulceration, which was alleviated by administration of octreotide possibly possessing antioxidant,anti-inflammatory,and anti-apoptotic actions.

Vitamin D_(3) attenuates anxiety-like behavior in long-term ovariectomized rats with unpredictable mild stress

The impact of various vitamin D3(VD3)doses(1.0,2.5,or 5 mg/kg,s.c.)in mitigating the negative consequences of chronic unpredictable mild stress(CUMS)was investigated.Adult female rats with long-term estrogen deficiency were assessed using the sucrose preference test(SPT),the elevated plus-maze(EPM),the light/dark test(LDT),and the open-field test(OFT)to measure anhedonia-like and anxiety-like behavior.The corticosterone(CS)and adrenocorticotrophic hormone(ACTH)concentrations in blood serum and the brain-derived neurotrophic factor(BDNF)expression in the hippocampus of long-term ovariectomized(OVX)rats were measured by ELISA kits and/or western blotting.Treatment with VD3(5.0 mg/kg),similarly to fluoxetine(10.0 mg/kg),significantly reduced the anhedonia profile in the SPT and anxiety-like behavior in the EPM and LDT,and CS and ACTH levels in blood serum.It also elevated BDNF levels in the hippocampus of long-term OVX/CUMS compared to OVX/CUMS/solvent rats.Thus,these findings suggest that VD3(5.0 mg/kg)administration might attenuate the anxiety-like profile in long-term OVX adult rats subjected to the CUMS.This might occur via activation of the BDNF signaling pathway in the hippocampus and via restoration of CS and ACTH levels in blood serum.

Shuganheweitang Ameliorates Chronic Unpredictable Mild Stress-Induced Depression-Like Behaviors in Rats through the PI3K/AKT/mTOR Pathway: Involvement of Amino Acids, Glycerophospholipids, and Energy Metabolism

Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like behaviors is still unclear. This study investigated the effects of SGHWT on metabolic change in the liver and hypothalamus with signaling pathways involved in chronic unpredictable mild stress (CUMS)-induced depression in rats to explore the mechanism of the anti-depressive effect. Methods: A total of 52 rats were used to create a model of depression by CUMS combined with solitary rearing for 6 weeks. Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and body weight (BW) were performed to analyze the pharmacodynamic effects of SGHWT. H&E staining, Nissl staining, immunofluorescence, immunohistochemistry, and western blot were used to evaluate the mechanism of action. Untargeted metabolomics techniques by ultra-performance liquid chromatography-quantitative time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to analyze all the metabolic differences in the liver and hypothalamus. Results: SGHWT improved CUMS-induced depression-like behaviors in vivo. SGHWT reduced hepatic c-Fos protein expression and increased hypothalamic c-Fos protein expression. Moreover, p-PI3K, p-AKT473, p-AKT308, and p-mTOR protein expressions were significantly downregulated in the liver and hypothalamus of CUMS rats. Notably, these alterations were reversed by the SGHWT administration. Furthermore, the metabolomic analysis identified 15 and 5 key differential SPT-associated metabolites in the liver and hypothalamus, respectively. Conclusion: This study suggests that SGHWT ameliorates chronic unpredictable mild stress-induced depression-like behaviors, by the involvement of amino acids, glycerophospholipids, energy metabolism, and the PI3K/AKT/mTOR pathway. Highlights: 1) Shuganheweitang was derived from the TCM herbal formula Sinisan. 2) SGHWT treatment reverses depression-like behaviors in CUMS-induced rats. 3) The mechanism of SGHWT on depression by the liver and hypothalamus metabolomics. 4) SGHWT regulates amino acids, glycerophospholipids, and energy metabolism. 5) SGHWT exerts antidepressant effects through the PI3K/AKT/mTOR pathway.

Jobelyn^(■), a Sorghum-Based Nutritional Supplement Attenuates Unpredictable Chronic Mild Stress-Induced Memory Deficits in Mice

The ability of an organism to adapt to aversive stressful situations or life challenging circumstances is very crucial to its state of health and survival. However, breakdown in adaptation due to persistent uncontrollable stress, leads to impairment of bodily functions and onset of a variety of pathological disorders especially memory decline. This study was designed to evaluate the effect of Jobelyn&reg;(JB), a potent antioxidant sorghum-based food supplement on unpredictable chronic mild stress (UCMS)-induced memory impairment in mice. Male Swiss mice were given JB (5 - 50 mg/kg, p.o) 30 min prior to exposure to UCMS for 14 consecutive days before testing for memory. Thereafter, the serum corticosterone level was estimated by using ELISA kits. The levels of malondialdehyde (MDA) and glutathione (GSH) as well as acetylcholinesterase activity were estimated in the brain homogenate using spectrophotometer. Histology of the brain tissues and estimation of the populations of viable neurons in the hippocampal region were done after staining with hematoxyline and eosin. Our results showed that JB reversed memory impairment and suppressed corticosterone concentrations induced by UCMS. Moreover, JB reduced oxidative stress in the brain of UCMS-mice as shown by decreased MDA levels and elevated GSH concentrations. It also decreased brain acetylcholinesterase activity when compared with chronic stress group (p < 0.05). Furthermore, JB (5 - 10 mg/kg, p.o) offered significant protection against UCMS-induced degeneration and death of neuronal cells of the cornu ammonis 3 (CA3) of the hippocampal region of the brain indicating neuroprotection. Taken together, these findings suggest that JB attenuates memory deficits induced by UCMS in mice and may be useful therapeutically for stress-related cognitive dysfunctions. The reduction in the levels of serum corticosterone, antioxidation, neuroprotection and inhibition of cholinesterase enzyme might be contributing significantly to the positive effect of JB on memory in mice exposed to unpredictable chronic mild stress.

Dynamic changes of behaviors, dentate gyrus neurogenesis and hippocampal miR-124 expression in rats with depression induced by chronic unpredictable mild stress

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.

Effect and mechanism of LW-AFC on chronic unpredictable mild stress-induced mood and cognition impairment of mice

OBJECTIVE To explore the effect and mechanisms of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on chronic unpredictable mild stress(CUMS)-induced mood and cogni.tion impairment in mice.METHODS C57 BL/6 J mice were randomly placed into seven groups(n=10):normal control group,CUMS group,Fluoxetine(10 mg·kg^(-1),once per day) group,Liuwei Dihuang decoction group(LW,10 g·kg^(-1),once per day),and LW-AFC(0.8 g·kg^(-1),1.6 g·kg^(-1),3.2 g·kg^(-1),once per day) group.The stressed group was given CUMS for 4 weeks to set up a chronic multiple-stressed model.LW and LW-AFC was oral administered a week prior to CUMS and until the end of the study(a total of 35 d),while fluoxetine was administrated orally for 4 weeks.The anxiety behavior was analyzed using the open field test(OFT) and elevated plus maze test(EPM).The depression behavior was ana.lyzed using the sucrose preference test(SPT) and forced swimming test(FST).Spatial cognition was evaluated using Morris water maze(MWM) test and working memory was evaluated using new object recognition test(NORT).RESULTS CUMS for 28 d increased depressive-and anxiety-like behaviors.LW-AFC(1.6 g·kg^(-1)) significantly increased the numbers of entries into the open arm and time in the open arm of CUMS mice(P<0.05).LW-AFC(3.2 g·kg^(-1)) increased sucrose consumption and de.creased the immobility time of FST(P<0.01) of CUMS mice.The MWM test showed that spatial learning andmemory in CUMS mice were remarkably affected relative to controls,whereas LW-AFC(3.2 g·kg^(-1)) im.proves cognitive functions(P<0.05).CONCLUSION The mood and theability of learning and memory of thestressed group can be affected after exposure to CUS.Oral administration of LW-AFC significant.ly improved CUMS-induced impairments of mood and cognition in mice.

Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Increased expression level of corticotropin-releasing hormone in the amygdala and in the hypothalamus in rats exposed to chronic unpredictable mild stress

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.

Antidepressant-like effect of essential oil of Perilla frutescens in a chronic, unpredictable, mild stress-induced depression model mice

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.

Antidepressant-Like Effects of Chaihu Shugan Powder(柴胡疏肝散)on Rats Exposed to Chronic Unpredictable Mild Stress through Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis

Objective:To investigate the antidepressant-like effects of Chaihu Shugan Powder(CSP,柴胡疏肝散)and to explore its underlying mechanisms.Methods:Thirty-two Sprague-Dawley rats were randomly divided into control(CON),chronic unpredictable mild stress(CUMS),fluoxetine(FLU),and CSP groups,8 rats in each group.All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model.The open field test(OFT),forced swimming test(FST),and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP.Terminal deoxynucleotidyl transferase(Td T)d UTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues.The m RNA and protein levels of glucose-regulated protein(GRP)78,spliced X-box-binding protein(XBP)-1,CCAAT/enhancerbinding protein homologous protein(CHOP),caspase-12,and c-Jun N-terminal kinase(JNK)in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis,respectively.Results:Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats,as revealed by enhanced time and distance in the center of the OFT(P<0.05),an increased preference for sucrose,and longer swimming time and shorter immobility time during the FST(all P<0.05).In addition,CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons(P<0.05).The m RNA and protein expression levels of GRP78,spliced XBP-1,and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins(all P<0.05),whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats.Conclusion:CSP can improve depression-like behavior in rats exposed to CUMS,possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.

Effects of Ning Shen Ling Granule (宁神灵冲剂) and Dehydroepiandrosterone on Cognitive Function in Mice Undergoing Chronic Mild Stress

Objective： To investigate the changes of spontaneous and cognitive behavior, and cholinergic M receptors in the brain of mice subjected to chronic mild stress （CMS）, and to determine the effect of Ning Shen Ling Granule （宁神灵冲剂, NSL） and dehydroepiandrosterone （DHEA） on them. Methods：CMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources, and they were medicated for 1 week beginning at the 3rd week of modeling. The changes in behavior were determined by Morris Water Maze and spontaneous movement test, and M-receptor binding activity in cerebral cortex, hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB. Results： （1） The spontaneous movement in CMS model mice was significantly reduced, with the latency for searching platform in Morris Water Maze obviously prolonged （P〈0.01）, and these abnormal changes in behavior were improved in those treated with NSL and DHEA. （2） The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group （P〈0.05）, but could be restored to the normal level after intervention with NSL or DHEA. Conclusion： The decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress, and that may be related to the low activity of central cholinergic M-receptors. Both NSL and DHEA could effectively alleviate the above-mentioned changes.

The Effect of Mild-Pressure Hyperbaric Therapy (Oasis O₂) on Fatigue and Oxidative Stress

Mild-pressure hyperbaric therapy (mHBT) has become increasingly popular among elite athletes and most recently among the general public yet there is very little scientific underpinnings on its therapeutic use. In this study, fifteen healthy volunteers (8 men, 7 women, mean age 29.7 ± 8.1 years) were exposed to 1.3 atmospheres absolute (ATA) for 40 minutes in a mild hyperbaric chamber called “Oasis O2” to determine the effect of ambient air at 1.3 ATA on oxidative stress, antioxidant potential, fatigue, and blood chemistry. Reactive oxygen metabolites (ROMs), an index of oxidative stress, significantly reduced by 11% (p = 0.006), while biological antioxidant potential (BAP), an index of antioxidant capacity, did not show a significant change (p = 0.749). WBC count significantly reduced by 10.4% (p = 0.005) whereas WBC differential did not show a marked change. The mean visual analog scale (VAS) score for fatigue significantly decreased from 5.0 to 2.1 (p < 0.001). Our findings suggest that mild-pressure hyperbaric therapy reduces oxidative stress as indicated by a significant decrease in serum ROM, and also helps improve fatigue as seen by a significant decrease in VAS fatigue scores.

Calculation of Wave Radiation Stress in Combination with Parabolic Mild Slope Equation

A new method for the calculation of wave radiation stress is proposed by linking the expressions for wave radiation stress with the variables in the parabolic mild slope equation. The governing equations are solved numerically by the finite difference method. Numerical results show that the new method is accurate enough, can be efficiently solved with little programming effort, and can be applied to the calculation of wave radiation stress for large coastal areas.

The Effect of the pH of Ammonum Nitrate Solution on the Susceptability of Mild Steel to Stress Corrosion Cracking (SCC) and General Corrosion

This work investigates the relative aggressiveness of nitrate solutions at different pH values on mild steel towards stress corrosion cracking (SCC) and general corrosion. Electrochemical behavior and stress corrosion cracking sus-ceptibility measurements were carried out in 52 Wt% ammonium nitrate solutions at 368° K and various pH values ranging from 0.77 to 9.64. Constant load stress corrosion test at 90% yield stress was conducted. Tested specimens were prepared and examined using the scanning electron microscope (SEM). The potentiodynamic polarization curves for different pH values again emphasized the validity of the gravimetric measurements and hence the mechanism of cracking was attributed to the stress that assisted the dissolution process.

Effect of Temperature and Concentration of Ammonium Nitrate Solution on the Succeptibility of Mild Steel to Stress Corrosion Cracking

The effect of varying the temperature and the concentration of ammonium nitrate solution on the stress corrosion cracking (SCC) susceptibility of mild steel is studied. An increase in the temperature causes a decrease in the stress corrosion life. It appears that the susceptibility in the range 368 K to 380 K was greater than at other temperatures. Near the boiling point corrosion and stress corrosion occurs, at the boiling point, the cracking was associated with a high rate of general corrosion. Microscopic examination after stress corrosion testing in 10Wt%, 20Wt%, and 52Wt% NH4NO3 solution revealed that in all cases there was severe intergranular attack, especially at the high concentration.

枣仁安神方对抑郁大鼠脑内单胺神经递质、HPA轴及CREB/BDNF信号通路的影响

目的:研究枣仁安神方(Zaoren Anshen Prescription,ZAP)对慢性不可预知温和应激(chronic mild unpredictable stress,CUMS)抑郁模型大鼠脑内单胺类神经递质、HPA轴功能及CREB/BDNF信号通路的影响,探讨其抗抑郁作用机制。方法:成年雄性SD大鼠随机分为正常对照组10只和模型组30只;正常对照组(CUMS-/Vehicle组)不给予任何处理,模型组给予孤养联合慢性不可预知温和应激,4周后再根据糖水偏好实验基线值评分将模型组大鼠分为3个亚组,分别为抑郁模型组(CUMS+/Vehicle组)、氟西汀阳性对照组(CUMS+/FLU组)和枣仁安神方治疗组(CUMS+/ZAP组)。各组均在造模时灌胃给药,给药时间为4周,CUMS-/Vehicle组大鼠给予0.9%生理盐水10 mL/(kg·d),CUMS+/ZAP组给予枣仁安神方15 g/(kg·d),CUMS+/FLU组给予FLU 10 mg/(kg·d)。实验结束后进行旷场实验、糖水偏好实验、强迫游泳实验和新环境进食抑制实验观察。应用高效液相色谱法检测大鼠海马组织单胺类神经递质及其代谢产物的浓度;采用酶联免疫吸附测定法检测各组大鼠血清促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、皮质酮(corticosterone,CORT)含量;采用Western blot检测大鼠海马组织中p-CREB、BDNF蛋白表达含量。结果:造模8周(ZAP治疗4周)后,与CUMS-/Vehicle组相比,CUMS+/Vehicle组大鼠体质量增量明显降低(P<0.01),糖水偏好显著降低(P<0.01),中心区域停留时间以及中心区域停留次数均减少(P<0.01),强迫游泳中不动时间显著增加(P<0.01),在新环境下的摄食潜伏期显著延长(P<0.01),血清ACTH、CORT的含量明显升高(P<0.01),海马组织单胺类神经递质水平显著降低(P<0.01),海马组织BDNF、p-CREB蛋白表达降低(P<0.01)。在应激持续存在的情况下,给予枣仁安神方治疗,上述异常的指标均得到明显改善,差异均有统计学意义(P<0.05,P<0.01)。结论:枣仁安神方可有效改善抑郁模型大鼠的行为学指标,可通过提高海马单胺类神经递质的水平、抑制HPA轴活性及增强海马p-CREB、BDNF表达,从而发挥其抗抑郁的作用。

Citrus aurantium L. extract alleviate depression by inhibiting gut microbiota-mediated inflammation in mice

Gut microbiota plays a crucial role in the pathophysiology of depression.This study aimed to explore the antidepressant effect of mature whole Citrus aurantium fruit extract(FEMC)in the chronic unpredictable mild stress(CUMS)model.The behavioral tests were applied to assess antidepressant effect and 16S rRNA sequencing was used to analyze the changes of gut microbiota.The results showed that the major components of FEMC were naringin and neohesperidin and significantly increased the sucrose preference index of the mice.FEMC also could reduce the feeding latency in an open field test and the rest time in a novelty suppressed feeding test.In addition,FEMC could increase CUMS-induced reduction in the levels of BDNF,PSD95,and SYN in the hippocampus.Moreover,FEMC intervention slightly decreased the ratio of Firmicutes to Bacteroidota.Meanwhile,FEMC reduced the abundance of the Prevotellaceae_Ga6A1_group,[Ruminococcus]_torques_group,which have been reported to be closely related to inflammation.Bioinformatics analysis revealed that mitogen-activated protein kinase(MAPK)signaling pathway and lipopolysaccharide biosynthesis were involved in the anti-inflammatory effect of FEMC in the CUMS animal model.Finally,the ELISA results showed that FEMC could significantly reduce the expression of pro-inflammatory cytokines IL-6 and TNF-αin the serum of depressive mice.Our results suggest FEMC can am eliorate depressive behavior by i nhibiting gut microbiota-mediated inflammation in mice.

Quercetin regulates depression-like behavior in CUMS rat models via TLR4/NF-κB signaling

Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.However,additional research is needed to dissect the mechanisms of its anti-depressive effects.Methods:For this study,Sprague-Dawley(SD)rats were randomized into the control,model,quercetin,or fluoxetine group.The latter three groups were exposed to chronic unpredictable mild stress(CUMS)for 42 d.The first two groups received saline solution daily via oral gavage.Meanwhile,the quercetin group was orally administered a quercetin suspension(52.08 mg/kg)every day,while the fluoxetine group was orally administered a fluoxetine solution(2.08 mg/kg).Here,fluoxetine served as the positive control drug to compare the therapeutic effects of quercetin.The experimental period was 6 weeks.Depressive behaviors in rats were assessed through various physiological and behavioral measures.Additionally,pathological changes in hippocampal tissues were examined using Nissl staining.Serum cytokines were detected using an enzymelinked immunosorbent assay(ELISA),and immunohistochemistry was employed to quantify the levels and integral optical density(IOD)values of ionized calcium binding adaptor molecule-1(Iba-1)expression in the brain.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to evaluate the mRNA levels of inflammatory indicators as well as toll-like receptor 4(TLR4),and nuclear factor-κappa B P65(NF-κB P65)in hippocampus.Western blot(WB)technique was employed to observe the protein levels of TLR4,NF-κB P65,and phospho-NF-κB P65(p-NF-κB P65).Results:After 42 d of exposure to CUMS,rats exhibited a slow increase in body weight,a reduction in food intake,an abnormal preference for sugar water,and aberrant open-field behaviors.Pathological analysis revealed the disintegration,rupture,interruption,and disorganization of hippocampal neuronal cells after CUMS exposure,along with a decrease in Nissl bodies in the CA1 region.This was accompanied by the elevated expression of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in the serum and the upregulation of IL-1β,IL-6,and TNF-αmRNA expression in the hippocampus.Increases in Iba-1-positive cells and the IOD values of Iba-1 were detected in hippocampal microglia.Furthermore,TLR4 and NF-κB P65 mRNA and protein levels were upregulated in hippocampal tissues.Quercetin,an antidepressant,could alleviate depression-like symptoms in rats and downregulate inflammatory factors associated with the TLR4/NF-κB signaling pathway in hippocampal microglia,and its therapeutic effect was comparable to fluoxetine.Conclusion:In rat models of CUMS,quercetin may act as an antidepressant by inhibiting inflammation in hippocampal microglia via TLR4/NF-κB signaling pathway.These results offer experimental and theoretical support for applying quercetin in the clinical management of depression.

X形软钢阻尼器延性断裂的试验研究与数值模拟

为了研究X形软钢阻尼器在大变形状态下的耗能性能和损伤演化规律,设计了6组试件进行单向和循环荷载作用下延性断裂的试验研究,分析了软钢阻尼器的破坏过程和滞回曲线。采用Lemaitre-Chaboche混合强化模型,分别对各工况下包含与不包含基于应力三轴度的钢材微观损伤模型的软钢阻尼器进行了精细的有限元模拟。对比有限元模拟结果和试验结果,分析结果表明,颈部为X形耗能软钢阻尼器的薄弱位置,最容易发生集中损伤甚至破坏。考虑钢材损伤准则的有限元模拟的荷载-位移曲线与试验结果更加吻合,能够表征软钢阻尼器的承载力与刚度退化现象,并能较为准确地预测软钢阻尼器的损伤演化过程和断裂破坏位置。