Glucocorticoids (GCs) can modulate the memory enhancement process during stressful events, and this modulation requires arousal-induced norepinephrine (NE) activation in the basolateral amygdale ...(BLA). Our previous study found that an intrahippocampal infusion of propranolol dose-dependently induced post-traumatic stress disorder (PTSD)-like memory impairments. To explore the role of the noradrenergic system of the BLA in PTSD-like memory impairment, we injected various doses of NE into the BLA. We found that only a specific quantity of NE (0.3 μg) could induce PTSD-like memory impairments, accompanied by a reduction in phosphorylation of GluR1 at Ser845 and Ser831. Moreover, this phenomenon could be blocked by a protein kinase A (PKA) inhibitor or calcium/calmodulin-dependent protein kinase II (CaMK II) inhibitor. These findings demonstrate that NE could induce PTSD-like memory impairments
regulation of the β-adrenoceptor receptor (β-AR)-3',5'-cyclic monophosphate (cAMP)/PKA and CaMK II/PKC signaling pathways.
•We developed a nonseasonal depression model with diurnal gerbils.•Light therapy improved CUMS-based depression in diurnal gerbils.•Light could improve depression-like behavior more effectively than ...fluoxetine.
Progress has been made in elucidating the mechanism by which light modulates depressive-like behaviors. However, almost all of these studies ignore an important issue, namely, that examining the effects of light therapy in nocturnal animals may be difficult because the influences of light on behavioral responses differ between nocturnal and diurnal animals. To date, few diurnal rodents have been utilized to establish animal models that closely mimic clinical depression. Herein, the chronic unpredictable mild stress model, which is the most representative, reliable, and effective rodent model of depression, was implemented in diurnal Mongolian gerbils for the first time. The gerbils were subjected to two hours of light therapy or fluoxetine treatment for 2 weeks. Our work revealed that Mongolian gerbils subjected to chronic unpredictable mild stress showed depression-like behaviors. Interestingly, we also found that light therapy improved anhedonic behavior more effectively than fluoxetine after two weeks of treatment. In summary, our study is the first to use diurnal Mongolian gerbils, which have the same circadian rhythm as humans, to establish an effective, economical, and practical animal model of depression and confirmed that light therapy could improve depression-like behavior more effectively than fluoxetine to some extent in diurnal Mongolian gerbils, which establishes a good foundation for clarifying the neural mechanism of light therapy for depression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We perform an investigation on the influence of phosphor particle size on visual and non-visual performances of white light-emitting diodes (LEDs) applied in the healthy general lighting. These ...studied white LEDs with a chip-scale packaging (CSP) structure are consisted of blue, green, and red phosphors, which are pumped by 365 nm near-ultraviolet LEDs. The monte carlo ray tracing based optical simulation and Mie scattering theory in LightTools softwares are adopted in this study. After optical simulation and spectral calculation, the circadian action factor (CAF) and other relevant parameters are deduced from spectral power distributions of white LEDs. Finally, the micro hyper-spectral imaging technique is employed for detecting micro-level luminescences of large (diameter <inline-formula> <tex-math notation="LaTeX">D </tex-math></inline-formula> = <inline-formula> <tex-math notation="LaTeX">20 ~\mu \text{m} </tex-math></inline-formula>) and small (<inline-formula> <tex-math notation="LaTeX">D </tex-math></inline-formula> = <inline-formula> <tex-math notation="LaTeX">10 ~\mu \text{m} </tex-math></inline-formula>) phosphor particles, indicating that small phosphor particles would scatter more light than large ones, leading to low luminous output and low CAF at the same time.
Background:
Late-life suicide is a severe public health problem in rural China; however, knowledge regarding the specific characteristics and risk factors for completed suicide via violent and ...non-violent methods among elderly individuals in rural China is limited.
Methods:
Subjects aged 60 years or older were selected from rural areas in Shandong, Hunan, and Guangxi provinces in China. This study was a 1:1 matched case-control design conducted by using the psychological autopsy method.
Results:
According to the univariate analyses, the presence of mental disorder, higher degree of depression, loneliness, lack of social support, hopelessness, impulsivity, and increased quantity of life events were associated with suicide in both violent and non-violent methods. For violent suicide, another risk factor was the lack of pesticides at home. For non-violent suicide, other risk factors were not currently married, family suicide history, and alcohol use disorder (
P
< 0.05). Variables that remained in the logistic regression model were the severity of depressive symptoms for both violent and non-violent suicide. For non-violent suicide, the degree of hopelessness was another independent risk factor. In addition, violent suicides were more likely to lack pesticides at home, choose the spring season and have an increased quantity of life events than those who died by suicide via non-violent methods.
Conclusion:
The major risk factor for both violent and non-violent suicide was the severity of depressive symptoms. Suicide prevention measures that focus on depression among this vulnerable population are urgently needed. Moreover, the characteristics of suicides via violent methods differed from those via non-violent methods among elderly individuals. Suicide prevention efforts should be tailored to the specific characteristics of the different suicide methods utilized by older adults in rural areas.
Background:
The most frequently used means of committing suicide was pesticide poisoning in rural China, yet little is known about the characteristics and risk factors for suicides committed with ...pesticides compared to those committed via other means in older adults.
Methods:
The participants were 242 older adults (aged 60 or older) who had committed suicide in the rural areas of 3 provinces (Shandong, Hunan, and Guangxi) in China. This study was conducted using the psychological autopsy (PA) method.
Results:
In univariate analyses, no statistically significant differences were found between those who committed suicide with pesticide or with other means in terms of demographic and clinical variables except age, prevalence of mental disorders, suicidal intent, number of recent life events, social support, hopelessness, impulsivity, and depressive symptoms (P > .05); age, history of suicide attempts, having pesticides available at home, the total number of life events, and the number of long-term life events were significantly different (P < .05) between the 2 groups. In multivariate logistic regression model, the factors associated with committing suicide with pesticides were the availability of pesticides at home (odds ratio OR = 3.48, 95% confidence interval CI: 1.99-6.08) and the number of long-term life events (OR = 0.87, 95% CI: 0.78-0.97).
Conclusion:
The older adults who committed suicide by pesticides and those using other means are probably the same population. The main determinant of choosing pesticides as suicide means was likely the availability of pesticides at home. Suicide risk among older adults might be reduced by placing appropriate restrictions on access to pesticides.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Microfilaments and microtubules, two crucial structures of cytoskeletal networks, are usurped by various viruses for their entry, egress, and/or intracellular trafficking, including the Rabies virus ...(RABV). Intermediate filaments (IFs) are the third major component of cytoskeletal filaments; however, little is known about the role of IFs during the RABV infection. Here, we identified the IF protein desmin as a novel host interactor with the RABV matrix protein, and we show that this physical interaction has a functional impact on the virus lifecycle. We found that the overexpression of desmin facilitates the RABV infection by increasing the progeny virus yield, and the suppression of endogenous desmin inhibits virus replication. Furthermore, we used confocal microscopy to observe that the RABV-M co-localizes with desmin in IF bundles in the BHK-21 cells. Lastly, we found that mice challenged with RABV displayed an enhanced expression of desmin in the brains of infected animals. These findings reveal a desmin/RABV-M interaction that positively regulates the virus infection and suggests that the RABV may utilize cellular IFs as tracks for the intracellular transport of viral components and efficient budding.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction
One hallmark symptom of post‐traumatic stress disorder (PTSD) is an inability to restrict fear responses to the appropriate predictor. An infusion of glucocorticoids (GCs) after a ...high‐intensity shock has been shown to induce PTSD‐like memory impairments. In addition to GCs, noradrenergic signalling is also recognized as a key biomarker underlying PTSD symptomatology.
Methods
To explore the role of the noradrenergic system in PTSD‐like memory impairments, in this study, various doses of the β‐adrenoceptor antagonist propranolol were systemically or bilaterally injected into the dorsal hippocampus immediately after unpaired cue‐shock contextual fear conditioning, and then the rats were tested 24 h later.
Results
Interestingly, we found that only low‐dose propranolol could induce PTSD‐like memory impairments, as rats showed reduced freezing to the correct predictor and generalized fear responses to the safe cues, accompanied by increased NE levels in the hippocampus and altered neural activity within the frontal‐subcortical circuit.
Conclusion
These findings demonstrate that the noradrenergic system is involved in regulating the consolidation of contextual fear memory and that propranolol can dose‐dependently induce PTSD‐like memory impairments.
Low‐dose propranolol can induce PTSD‐like memory impairments. The propranolol's effect of PTSD‐like memory impairments showed hippocampus region specificity. The increased NE levels in the hippocampus and altered neural activity within the frontal‐subcortical circuit may be the possible regulatory mechanism which the low‐dose propranolol induced PTSD‐like memory impairments.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
HSP110 functions to protect cells, tissues, and organs from noxious conditions. Vasectomy induces apoptosis in the testis; however, little is known about the reason leading to this outcome. The aim ...of the present study was to evaluate the expression and function of HSP110 in mouse testis after vasectomy. Following bilateral vasectomy, we used fluorescent Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） to detect apoptosis, Western blotting and immunohistochemistry to examine HSP110 expression and localization. Serum antisperm antibody （AsAb） and testosterone were measured by Enzyme-linked immunosorbent assay （ELISA） and radioimmunoassay, respectively. Expression of endoplasmic reticulum stress （ERS） sensors and downstream signaling components was measured by Reverse Transcription-Polymerase Chain Reaction （RT-PCR）, and the phosphorylation of elF2a and JNK was detected by Western blotting. Vasectomy induced morphologic changes, increased apoptosis in the testis, increased serum AsAb, and decreased testosterone levels. After vasectomy, ORP150 mRNA level was increased first and then decreased, Bcl-2 was decreased, and the expression of HSPA41, GRP78, GADD153, PERK, ATF6, IRE-l, XBP-ls, Bax, Bak, and caspases and the phosphorylation of elF2a and JNK were increased. We present that an ER stress-mediated pathway is activated and involved in apoptosis in the testis after vasectomy. HSPA41 and ORP150 may play important roles in maintaining the normal structure and function of testis.
Brain metastasis (BM) is one of the most common metastatic sites in patients with small cell lung cancer (SCLC), and the prognosis remains very poor. This study aimed to establish a novel nomogram ...for predicting the cancer-specific survival (CSS) in SCLC patients with BM.
SCLC patients with BM from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were retrospectively collected. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors, which were further used to construct the prognostic nomogram. The discrimination and calibration of nomogram were evaluated by concordance index (C-index), receiver operating characteristic (ROC) curve, the area under ROC curve (AUC) and calibration plot. Decision curve analysis (DCA) was used to assess the clinical usefulness. Kaplan-Meier survival curve was applied to analyze the survival outcome.
A total of 2,462 patients were enrolled in this study, and randomly assigned into training cohort (n=1,723) and validation cohort (n=739). Age, N stage, surgery, radiation, chemotherapy, bone metastasis, liver metastasis and lung metastasis were identified as independent prognostic factors of CSS. The C-indexes of nomogram was 0.683 95% confidence interval (CI): 0.667-0.699 in the training cohort, and 0.659 (95% CI: 0.634-0.684) in the validation cohort. The AUC values of 6-, 9- and 12-month CSS were 0.723, 0.742 and 0.737 respectively in the training cohort, while 0.715, 0.737 and 0.739 in the validation cohort. The ROC, calibration and DCA curves showed good discrimination, calibration and clinical applicability of this nomogram in predicting prognosis. Moreover, patients in high-risk group had a worse survival outcome than patients in medium-risk and low-risk groups.
A novel nomogram was constructed and validated for predicting individual prognosis in SCLC patients with BM. This nomogram could help clinicians make effective treatment strategies for patients.
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