A comprehensive survey on computational methods of non-coding RNA and disease association prediction.

The studies on relationships between non-coding RNAs and diseases are widely carried out in recent years. A large number of experimental methods and technologies of producing biological data have also been developed. However, due to their high labor cost and production time, nowadays, calculation-based methods, especially machine learning and deep learning methods, have received a lot of attention and been used commonly to solve these problems. From a computational point of view, this survey mainly introduces three common non-coding RNAs, i.e. miRNAs, lncRNAs and circRNAs, and the related computational methods for predicting their association with diseases. First, the mainstream databases of above three non-coding RNAs are introduced in detail. Then, we present several methods for RNA similarity and disease similarity calculations. Later, we investigate ncRNA-disease prediction methods in details and classify these methods into five types: network propagating, recommend system, matrix completion, machine learning and deep learning. Furthermore, we provide a summary of the applications of these five types of computational methods in predicting the associations between diseases and miRNAs, lncRNAs and circRNAs, respectively. Finally, the advantages and limitations of various methods are identified, and future researches and challenges are also discussed.

Identifying Cancer genes by combining two-rounds RWR based on multiple biological data.

BACKGROUND: It's a very urgent task to identify cancer genes that enables us to understand the mechanisms of biochemical processes at a biomolecular level and facilitates the development of bioinformatics. Although a large number of methods have been proposed to identify cancer genes at recent times, the biological data utilized by most of these methods is still quite less, which reflects an insufficient consideration of the relationship between genes and diseases from a variety of factors. RESULTS: In this paper, we propose a two-rounds random walk algorithm to identify cancer genes based on multiple biological data (TRWR-MB), including protein-protein interaction (PPI) network, pathway network, microRNA similarity network, lncRNA similarity network, cancer similarity network and protein complexes. In the first-round random walk, all cancer nodes, cancer-related genes, cancer-related microRNAs and cancer-related lncRNAs, being associated with all the cancer, are used as seed nodes, and then a random walker walks on a quadruple layer heterogeneous network constructed by multiple biological data. The first-round random walk aims to select the top score k of potential cancer genes. Then in the second-round random walk, genes, microRNAs and lncRNAs, being associated with a certain special cancer in corresponding cancer class, are regarded as seed nodes, and then the walker walks on a new quadruple layer heterogeneous network constructed by lncRNAs, microRNAs, cancer and selected potential cancer genes. After the above walks finish, we combine the results of two-rounds RWR as ranking score for experimental analysis. As a result, a higher value of area under the receiver operating characteristic curve (AUC) is obtained. Besides, cases studies for identifying new cancer genes are performed in corresponding section. CONCLUSION: In summary, TRWR-MB integrates multiple biological data to identify cancer genes by analyzing the relationship between genes and cancer from a variety of biological molecular perspective.

[4 + 2] Cyclization of para-Quinone Methide Derivatives with Alkynes.

The first cyclization of para-quinone methide derivatives with alkynes was established by utilizing the [4 + 2] reaction of ortho-hydroxyphenyl-substituted para-quinone methides with ynones or benzyne, which efficiently constructed the scaffolds of chromene and xanthene in high yields (up to 88%). This protocol has not only fulfilled the task of developing cyclization reactions of para-quinone methide derivatives but also provided an efficient method for constructing chromene and xanthene scaffolds.

Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude.

INTRODUCTION: Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH. METHODS: Minipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH. RESULTS: High-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated. CONCLUSIONS: The data suggested a more serious disturbance of tissue oxygenation and cerebral metabolism in the acute stage after ICH at high altitude. Early HBO treatment reduced acute brain injury, perhaps through a mechanism involving the amelioration of the derangement of cerebral oxygenation and metabolism following high-altitude ICH.

Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with potent anti-inflammatory properties that is extracted from the rhizome Curcuma longa, alleviates acute inflammatory injury mediated by TLR4 following TBI. METHODS: Neurological function, brain water content and cytokine levels were tested in TLR4⁻/⁻ mice subjected to weight-drop contusion injury. Wild-type (WT) mice were injected intraperitoneally with different concentrations of curcumin or vehicle 15 minutes after TBI. At 24 hours post-injury, the activation of microglia/macrophages and TLR4 was detected by immunohistochemistry; neuronal apoptosis was measured by FJB and TUNEL staining; cytokines were assayed by ELISA; and TLR4, MyD88 and NF-κB levels were measured by Western blotting. In vitro, a co-culture system comprised of microglia and neurons was treated with curcumin following lipopolysaccharide (LPS) stimulation. TLR4 expression and morphological activation in microglia and morphological damage to neurons were detected by immunohistochemistry 24 hours post-stimulation. RESULTS: The protein expression of TLR4 in pericontusional tissue reached a maximum at 24 hours post-TBI. Compared with WT mice, TLR4⁻/⁻ mice showed attenuated functional impairment, brain edema and cytokine release post-TBI. In addition to improvement in the above aspects, 100 mg/kg curcumin treatment post-TBI significantly reduced the number of TLR4-positive microglia/macrophages as well as inflammatory mediator release and neuronal apoptosis in WT mice. Furthermore, Western blot analysis indicated that the levels of TLR4 and its known downstream effectors (MyD88, and NF-κB) were also decreased after curcumin treatment. Similar outcomes were observed in the microglia and neuron co-culture following treatment with curcumin after LPS stimulation. LPS increased TLR4 immunoreactivity and morphological activation in microglia and increased neuronal apoptosis, whereas curcumin normalized this upregulation. The increased protein levels of TLR4, MyD88 and NF-κB in microglia were attenuated by curcumin treatment. CONCLUSIONS: Our results suggest that post-injury, curcumin administration may improve patient outcome by reducing acute activation of microglia/macrophages and neuronal apoptosis through a mechanism involving the TLR4/MyD88/NF-κB signaling pathway in microglia/macrophages in TBI.

Enhancement of ester biosynthesis in blueberry wines through co-fermentation via cell-cell contact between Torulaspora delbrueckii and Saccharomyces cerevisiae.

This study investigated the effects of co-fermentation of T. delbrueckii and S. cerevisiae on the volatile composition and sensory characteristics of blueberry wines. Mixed fermentation led to higher levels of terpenes, higher alcohols, and esters compared to wines fermented with each yeast individually. Conversely, when T. delbrueckii were physically separated from S. cerevisiae in the double-compartment fermenter, contrasting outcomes emerged. The stronger fruity aroma induced by mixed fermentation were linked to higher ester concentrations, including isoamyl acetate, ethyl isovalerate, ethyl hexanoate, and diethyl succinate. The enhanced esters in mixed fermentation can be attributed to the upregulated alcohol acyltransferase activity and the expressions of ACC1, FAS2, ELO1 and ATF1 genes in late fermentation stage via the cell-cell contact between T. delbrueckii and S. cerevisiae. These findings can deepen the understanding of the interaction between non-Saccharomyces and S. cerevisiae in ester production, assisting wineries in effectively controlling wine aroma through mixed fermentations.

Imaging findings of hepatocellular carcinoma with portal vein tumor thrombosis secondary to hepatic portal vein collateral circulation: a cross-sectional study.

Background: Hepatic portal vein collateral circulation plays an important role in maintaining the perfusion of hepatic portal vein. However, at present, there is little research on collateral circulation of hepatic portal vein. Our study aims to analysis the imaging types and clinical value of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) invading and completely blocking different branches of portal vein, secondary to hepatic portal vein collateral circulation. Methods: This study retrospectively analyzed Hepatocellular carcinoma (HCC) with PVTT diagnosed with enhanced CT examination of the upper abdomen in our hospital from May 2020 to October 2021.The inclusion criteria for patients were the following: (I) ultimately diagnosed with HCC, (II) accompanied by complete obstruction of the main portal vein or left/right branches, and (III) with collateral circulation of the hepatic portal vein established. All images were postprocessed by multiplanar reconstruction (MPR), maximum intensity projection (MIP), and other reconstruction techniques to obtain images of the abnormal portal vein system and the collateral vessels running toward the hepatic portal veins. Three physicians jointly judged the imaging anatomical classification of each collateral vessel. The qualitative variables were compared by chi-squared test. Results: A total of 125 hepatic portal vein collateral vessels were observed in MPR and MIP reconstruction images of 71 patients with portal vein cancer thrombosis with established hepatic portal vein collateral circulation. Common hepatic collateral branches in patients with PVTT mainly include the biliary collateral branch, gastric collateral branch, mesenteric collateral branch, accessory portal vein system and the splenic branch. The incidence rate was respectively 77.5%, 36.6%, 32.4%, 28.2%, 1.41%. Conclusions: The correct understanding of the imaging anatomical classification of the collateral vessels of the hepatic portal vein can provide clinicians with more information for diagnosis and treatment planning.

Microglial TIR-domain-containing adapter-inducing interferon-ß (TRIF) deficiency promotes retinal ganglion cell survival and axon regeneration via nuclear factor-κB.

BACKGROUND: TIR-domain-containing adapter-inducing interferon-ß (TRIF) is the sole downstream adaptor of Toll-like receptor (TLR)3, which is one of the major signaling pathways in immune cells leading to neuroinflammation in the central nervous system. Overexpression of TRIF may lead to activation of inflammatory responses, and contribute to pathophysiological progression in both acute and chronic neurodegenerative retinal diseases. In the present study, was aimed to elucidate the contributions of TRIF to optic nerve (ON) regeneration and retinal ganglion cell (RGC) survival following injury to the ON, a widely studied model of central nervous system injury and of degenerative diseases such as glaucoma. METHODS: We used retrograde labeling with a fluorochrome, hydroxystilbamidine (Fluorogold) to evaluate RGC survival, and immunostaining with growth-associated protein-43 to evaluate axon regeneration in an ON crush model. Changes in microglial cytokines following RGC injury was examined with ELISA and real-time PCR. In vivo studies were carried out in wild-type and trif-/- mice. A Transwell co-culture system and migration test were used to mimic the crosstalk between microglia and RGCs. TRIF-associated downstream adaptors were determined by western blotting. RESULTS: Compared with wild-type (WT) mice, TRIF knockout (KO) mice displayed a robust ability to regenerate axons 3 or 7 days after nerve injury. In addition, RGC survival was considerably higher in trif-/- than in WT mice. ON lesion induced less microglial activation in trif-/- than in WT mice. and more WT microglia distorted and migrated toward the foramen opticum. In the transwell system, few trif-/- microglia migrated through the membrane when stimulated by the performed lesion on RGC axons in a transwell system. Inactivation of microglial cells in trif-/- mice was associated with reduced production of inflammatory cytokines, as detected with real-time RT-PCR and ELISA. Furthermore western blot analysis showed that activation of known downstream effectors of TRIF, including TBK1, IKKε and NF-κB, were significantly inhibited by TRIF deficiency. CONCLUSION: Our results indicate that TRIF deficiency promotes ON axon regeneration by attenuating microglial activation and consequently reducing the release of harmful cytokines via NF-κB inactivation.

Gonadectomy differentially regulates steroid receptor coactivator-1 and synaptic proteins in the hippocampus of adult female and male C57BL/6 mice.

Hippocampus is one of the most important structures that mediates learning and memory, cognition, and mental behaviors and profoundly regulated by sex hormones in a sex-specific manner, but the mechanism of underlying sex differences regulation is still unclear. We have previously reported that in the male and female mice, steroid receptor coactivator-1 (SRC-1) and some key synaptic proteins share similar developmental profile in the hippocampus, but how circulating sex hormones affect hippocampal SRC-1 as well as these synaptic proteins remain unclear. In this study, we examined how gonad sex hormones regulate hippocampal SRC-1, synaptophysin, PSD-95, and AMPA receptor subtype GluR1 by using immunohistochemistry and Western blot. The results showed that in the female mice, ovariectomy affected hippocampal SRC-1 and GluR1 were only detected at 2 weeks post operation, then it recovered to sham level; synaptophysin was unaffected at any timepoint examined; significant decrease of PSD-95 was only detected at 4 weeks post operation. However, in the male hippocampus, SRC-1 and PSD-95 were decreased from one week and lasted to 4 weeks after orchidectomy, GluR1 decreased from 2 weeks after orchidectomy, but synaptophysin remained unchanged as in the females. Correlation analysis showed the profiles of SRC-1 were positively correlated with GluR1 of the females, PSD-95 and GluR1 of the males, respectively. The above results suggested a distinct regulatory mode between female and male gonad hormones in the regulation of hippocampal SRC-1 and synaptic proteins, which may be one of the mechanisms contributing to the dimorphism of hippocampus during development and ageing.

Steroid receptor coactivator-1: The central intermediator linking multiple signals and functions in the brain and spinal cord.

The effects of steroid hormones are believed to be mediated by their nuclear receptors (NRs). The p160 coactivator family, including steroid receptor coactivator-1 (SRC-1), 2 and 3, has been shown to physically interact with NRs to enhance their transactivational activities. Among which SRC-1 has been predominantly localized in the central nervous system including brain and spinal cord. It is not only localized in neurons but also detectable in neuroglial cells (mainly localized in the nuclei but also detectable in the extra-nuclear components). Although the expression of SRC-1 is regulated by many steroids, it is also regulated by some non-steroidal factors such as injury, sound and light. Functionally, SRC-1 has been implied in normal function such as development and ageing, learning and memory, central regulation on reproductive behaviors, motor and food intake. Pathologically, SRC-1 may play a role in the regulation of neuropsychiatric disorders (including stress, depression, anxiety, and autism spectrum disorder), metabolite homeostasis and obesity as well as tumorigenesis. Under most conditions, the related mechanisms are far from elucidation; although it may regulate spatial memory through Rictor/mTORC2-actin polymerization related synaptic plasticity. Several inhibitors and stimulator of SRC-1 have shown anti-cancer potentials, but whether these small molecules could be used to modulate ageing and central disorder related neuropathology remain unclear. Therefore, to elucidate when and how SRC-1 is turned on and off under different stimuli is very interesting and great challenge for neuroscientists.

Critical Path-Based Backdoor Detection for Deep Neural Networks.

Backdoor attack to deep neural networks (DNNs) is among the predominant approaches to bring great threats into artificial intelligence. The existing methods to detect backdoor attacks focus on the perspective of distributions in DNNs, however, limited by its ability of generalization across DNN models. In this article, a critical-path-based backdoor detector (CPBD) is proposed, which approaches to detect backdoor attacks via DNN's interpretability. CPBD is designed to efficiently discover the characteristics of backdoors, which distinguish the critical paths in the attacked DNNs. To deal with the intractably large number of neurons, we propose to simplify the neurons, and the preserved key nodes are integrated into a set of critical paths. Thus, a DNN model can be formulated as a combination of several critical paths. Afterward, the detection of backdoors is performed based on the analysis of critical paths corresponding to different classes. Then, combining all the above steps, the CPBD algorithm is integrated to present the results in a standard and systematic manner. In addition, CPBD is able to locate neurons associated with malicious triggers, the combination of which is named as trigger propagation path. Extensive experiments are conducted, which testify the efficiency of the proposed method on multiple DNNs and different trigger sizes.

The antimicrobial systems of Streptococcus suis promote niche competition in pig tonsils.

Streptococcus suis can cause severe infections in pigs and humans. The tonsils of pigs are major niches for S. suis, and different serotypes of S. suis can be found in the same tonsil. Pig tonsil colonization by S. suis is believed to be an important source of infection for humans and pigs. However, how S. suis competes for a stable tonsil niche is unknown. Here, we found that S. suis strain WUSS351, isolated from a healthy pig tonsil, is virulent and multidrug-resistant. The ABC transporter system SstFEG, conferring resistance to bacitracin, was reported to confer a competitive survival advantage in vivo. In addition, strain WUSS351 has several antimicrobial systems, including a novel type VII secretion system (T7SS), lantibiotic bacteriocin, and lactococcin972-like bacteriocin Lcn351. Bacterial competition experiments demonstrated T7SS-mediated cell contact-dependent antagonism of S. suis. Antibacterial activity analysis and 16S rRNA gene sequencing of the culture-independent and culture-dependent pig tonsillar microbiome revealed that Lcn351 mainly targets S. suis, one of the core microbiomes in pig tonsils. Taken together, our results revealed the mechanism of the stable persistence of S. suis in the tonsil niche, which might have important implications for S. suis epidemiology, potentially influencing strain prevalence and disease progression.

Expression of steroid receptor coactivator-1 was regulated by postnatal development but not ovariectomy in the hippocampus of rats.

Female steroids such as estrogens and progestins, through their nuclear receptors, play important roles in regulation of the structure and function of the hippocampus. Steroid receptor coactivator-1 (SRC-1) has been detected in embryonic and/or adult hippocampus of rodents, and SRC-1 null mice showed significantly longer escape latency in the Morris maze test, indicating a role of this coactivator in the regulation of hippocampus function. Whether this is regulated by development and circulating ovary hormones remains unclear. In this study, postnatal development and ovariectomy for regulation of hippocampal SRC-1 in female rats were investigated by Western blot and immunohistochemistry. The results showed that SRC-1-immunopositive materials were predominantly detected in the CA1 pyramidal cell layer and dentate gyrus granular cell layer. Very low levels of SRC-1 were detected at postnatal day 0, but they increased with development. The highest levels of SRC-1 were detected at postnatal day 14, then they decreased to adult levels from postnatal day 30; significantly lower levels of SRC-1 were detected in the middle-aged (18-month-old) hippocampus when compared with that of the adult. Western blot and immunohistochemistry demonstrated that hippocampal SRC-1 expression was unchanged after ovariectomy, no significant differences were noticed from day 3 to 8 weeks postsurgery when compared with sham animals. The above results showed that hippocampal SRC-1 is regulated by postnatal development but not ovariectomy, and that the exact role of SRC-1 in the estradiol regulation of hippocampus needs further investigation.

GATCDA: Predicting circRNA-Disease Associations Based on Graph Attention Network.

CircRNAs (circular RNAs) are a class of non-coding RNA molecules with a closed circular structure. CircRNAs are closely related to the occurrence and development of diseases. Due to the time-consuming nature of biological experiments, computational methods have become a better way to predict the interactions between circRNAs and diseases. In this study, we developed a novel computational method called GATCDA utilizing a graph attention network (GAT) to predict circRNA-disease associations with disease symptom similarity, network similarity, and information entropy similarity for both circRNAs and diseases. GAT learns representations for nodes on a graph by an attention mechanism, which assigns different weights to different nodes in a neighborhood. Considering that the circRNA-miRNA-mRNA axis plays an important role in the generation and development of diseases, circRNA-miRNA interactions and disease-mRNA interactions were adopted to construct features, in which mRNAs were related to 88% of miRNAs. As demonstrated by five-fold cross-validation, GATCDA yielded an AUC value of 0.9011. In addition, case studies showed that GATCDA can predict unknown circRNA-disease associations. In conclusion, GATCDA is a useful method for exploring associations between circRNAs and diseases.

The population structure, antimicrobial resistance, and pathogenicity of Streptococcus suis cps31.

Streptococcus suis is a zoonotic pathogen that can cause invasive infections in humans and pigs. The S. suis cps31 strains (SS31) were frequently isolated from healthy or diseased pigs and one human infection case caused by SS31 was reported in Thailand in 2015. However, except for a few epidemiologic studies, little information is available for SS31. To characterize SS31, a total of 75 SS31 strains were analyzed, including 52 strains that were isolated from healthy or diseased pigs and 23 strains whose information was accessed from NCBI. The MLST analysis showed that SS31 exhibited high heterogeneity. The phylogenetic analysis and minimum core-genome (MCG) classification revealed that 75 strains were clustered into 3 lineages. Strains from NCBI mainly at Lineage 2 belong to MCG7-3, and most of strains from China at Lineage 3 belong to MCG7-2. This finding indicated that their evolutionary path was different. All SS31 strains were resistant to more than three classes of antimicrobial agents, and major antimicrobial resistance genes for strains from Lineage 3 were carried by prophages. This observation is different from the previous observation that integrative conjugative elements and integrative and mobilizable elements are major vehicles of antimicrobial resistance genes for S. suis. In addition to strains isolated from diseased pigs, seven of 47 strains isolated from clinically healthy pigs were also pathogenic in a zebrafish infection model. These findings reveal unique characteristics of SS31 and contribute to establishing public health surveillance for SS31 and clarifying the diversity of S. suis.

Postnatal and ovariectomic regulation of postsynaptic density protein-95 in the hippocampus of female Sprague-Dawley rats.

Postsynaptic density protein-95 (PSD-95) is hypothesized to control the excitatory-to-inhibitory ratio and plays an important role in the regulation of hippocampal synaptic plasticity, synaptogenesis, and learning and memory. In this report, we used immunoblotting to study the effects of aging and ovariectomy (OVX) on the expression of PSD-95 in the hippocampus of female rats. The results indicated that postnatal expression of hippocampal PSD-95 correlated with the fluctuation of circulating female sex hormones such as estrogen. Neonatal PSD-95 level was very low, but dramatically increased within the first month. The highest expression of PSD-95 was detected at postnatal day 30 (P30) and significantly decreased by 18 months. In the adult hippocampus, OVX significantly decreased PSD-95 expression within the first week, but it had recovered to adult levels 2 weeks later. Taken together, we conclude that circulating ovarian hormones may play a crucial role in the regulation of excitatory synapses within the hippocampus. Depletion of ovarian hormones can transiently and dramatically decrease the level of excitatory synapses for a limited time.

Integrating random walk with restart and k-Nearest Neighbor to identify novel circRNA-disease association.

CircRNA is a special type of non-coding RNA, which is closely related to the occurrence and development of many complex human diseases. However, it is time-consuming and expensive to determine the circRNA-disease associations through experimental methods. Therefore, based on the existing databases, we propose a method named RWRKNN, which integrates the random walk with restart (RWR) and k-nearest neighbors (KNN) to predict the associations between circRNAs and diseases. Specifically, we apply RWR algorithm on weighting features with global network topology information, and employ KNN to classify based on features. Finally, the prediction scores of each circRNA-disease pair are obtained. As demonstrated by leave-one-out, 5-fold cross-validation and 10-fold cross-validation, RWRKNN achieves AUC values of 0.9297, 0.9333 and 0.9261, respectively. And case studies show that the circRNA-disease associations predicted by RWRKNN can be successfully demonstrated. In conclusion, RWRKNN is a useful method for predicting circRNA-disease associations.

Inhibition of steroid receptor coactivator-1 in the hippocampus impairs the consolidation and reconsolidation of contextual fear memory in mice.

AIMS: Steroid receptor coactivator-1 (SRC-1) is a key coactivator for the efficient transcriptional activity of steroids in the regulation of hippocampal functions. However, the effect of SRC-1 on hippocampal memory processes remains unknown. Our aim was to investigate the roles of hippocampal SRC-1 in the consolidation and reconsolidation of contextual fear memory in mice. MAIN METHODS: Contextual fear conditioning paradigm was constructed in adult male C57BL/6 mice to examine the fear learning and memory processes. Adeno-associated virus (AAV) vector-mediated RNA interference (RNAi) was infused into hippocampus to block hippocampal SRC-1 level. Immunofluorescent staining was used to detect the efficiency of transfection. High plus maze and open field test were used to determine anxiety and locomotor activity. Western blot analyses were used to detect the expression of SRC-1 and synaptic proteins in the hippocampus. KEY FINDINGS: We first showed that the expression of SRC-1 was regulated by fear conditioning training in a time-dependent manner, and knockdown of SRC-1 impaired contextual fear memory consolidation without affecting innate anxiety or locomotor activity. In addition, hippocampal SRC-1 was also regulated by the retrieval of contextual fear memory, and downregulation of SRC-1 disrupted fear memory reconsolidation. Moreover, knockdown of SRC-1 reversed the increased GluR1 and PSD-95 levels induced by contextual fear memory retrieval. SIGNIFICANCE: Our data indicate that hippocampal SRC-1 is required for the consolidation and reconsolidation of contextual fear memory, and SRC-1 may be a potential therapeutic target for mental disorders that are involved in hippocampal memory dysfunction.

Military Career Adaptability Questionnaire in China: Development and Validation.

OBJECTIVE: To develop the Military Career Adaptability Questionnaire (MCAQ) in China and to test its reliability and validity. METHODS: In study 1, an open-ended questionnaire survey was conducted among 200 military personnel. Based on the empirical construction by military personnel of various branches, the dimensions of the MCAQ were constructed, and a preliminary questionnaire was prepared. In study 2, the questionnaire survey was conducted in 1,578 participants enrolled through stratified cluster sampling. They were randomly divided into two groups (n = 789). Sample 1 was used for item analysis and exploratory factor analysis, and sample 2 was used for confirmatory factor analysis and internal consistency testing. In sample 1, the participants were selected to test the test-retest reliability of the questionnaire at a 4 weeks interval. In sample 2, participants were selected to test criterion validity using the Psychological Capital Questionnaire and the Job Satisfaction Questionnaire. RESULTS: According to study 1, we obtained an initial 23-item MCAQ containing five dimensions (organization and fusion ability, communication ability, learning development ability, emotion regulation ability, and career transformation ability). After the exploratory factor analysis in study 2, 21 items contributing 72.17% of the total variance remained. Via the subsequent confirmatory factor analysis, the model was confirmed to have good fit indices [chi-square/degree of freedom (X 2/df) = 3.11, goodness of fit index (GFI) = 0.90, normed fit index (NFI) = 0.91, incremental fit index (IFI) = 0.94, tucker lewis index (TLI) = 0.93, comparative fit index (CFI) = 0.94, standardized root mean square residual (SRMR) = 0.07]. These five factors were significantly correlated with the total score of the MCAQ (r = 0.73-0.79, p < 0.01). The Cronbach α coefficient of the questionnaire was 0.92; the Cronbach α coefficients of the five factors were 0.89, 0.83, 0.88, 0.84, and 0.79, respectively, the test-retest reliability of the questionnaire was 0.93. CONCLUSION: The MCAQ developed in this study has a clear five-factor structure and good reliability and validity. It can be used to assess the career adaptability of military personnel to provide a theoretical basis for military vocational psychological education.

Letrozole induces worse hippocampal synaptic and dendritic changes and spatial memory impairment than ovariectomy in adult female mice.

Estrogens (E2) derived from ovaries and/or local de novo synthesis in the hippocampus profoundly regulate hippocampal structure and function, but the importance of local E2 versus ovarian E2 on hippocampal synaptic plasticity and spatial memory has not been well elucidated. The present study used ovariectomy (OVX) and intraperitoneal injection of an E2 synthase inhibitor, letrozole (LET), in adult female mice to investigate changes in hippocampal steroid receptor coactivator-1 (SRC-1), postsynaptic proteins, and actin polymerization dynamics with these treatments. Changes in the CA1 spine density, synapse density and spatial learning and memory after OVX and LET were also investigated. As a result, OVX and LET showed similar regulation of the expression of GluR1, spinophilin and p-Cofilin, but LET tended to induce more significant changes in SRC-1, PSD95, Rictor, Cofilin and actin depolymerization. More significant decreases in F-actin/G-actin, CA1 spine density and synapse density were also observed after LET than after OVX. Notably, LET-treated mice showed worse learning and memory impairment than OVX mice. Taken together, these results demonstrated that circulating E2 played a limited role and that hippocampus-derived E2 played a more important role in the regulation of hippocampal synaptic plasticity and hippocampus-based spatial learning and memory.