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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Transcriptional Regulation Involved in Fear Memory Reconsolidation.

Memory reconsolidation has been demonstrated to offer a potential target period during which the fear memories underlying fear disorders can be disrupted. Reconsolidation is a labile stage that consolidated memories re-enter after memories are reactivated. Reactivated memories, induced by cues related to traumatic events, are susceptible to strengthening and weakening. Gene transcription regulation and protein synthesis have been suggested to be required for fear memory reconsolidation. Investigating the transcriptional regulation mechanisms underlying reconsolidation may provide a therapeutic method for the treatment of fear disorders such as post-traumatic stress disorder (PTSD). However, the therapeutic effect of treating a fear disorder through interfering with reconsolidation is still contradictory. In this review, we summarize several transcription factors that have been linked to fear memory reconsolidation and propose that transcription factors, as well as related signaling pathways can serve as targets for fear memory interventions. Then, we discuss the application of pharmacological and behavioral interventions during reconsolidation that may or not efficiently treat fear disorders.

Steroid Receptor Coactivator-1 Knockdown Decreases Synaptic Plasticity and Impairs Spatial Memory in the Hippocampus of Mice.

Steroids have been demonstrated to play profound roles in the regulation of hippocampal function by acting on their receptors, which need coactivators for their transcriptional activities. Previous studies have shown that steroid receptor coactivator-1 (SRC-1) is the predominant coactivator in the hippocampus, but its exact role and the underlying mechanisms remain unclear. In this study, we constructed SRC-1 RNA interference (RNAi) lentiviruses, injected them into the hippocampus of male mice, and then examined the changes in the expression of selected synaptic proteins, CA1 synapse density, postsynaptic density (PSD) thickness, and in vivo long-term potentiation (LTP). Spatial learning and memory behavior changes were investigated using the Morris water maze. We then transfected the lentiviruses into cultured hippocampal cells and examined the changes in synaptic protein and phospho-cyclic AMP response element-binding protein (pCREB) expression. The in vivo results showed that SRC-1 knockdown significantly decreased the expression of synaptic proteins and CA1 synapse density as well as PSD thickness; SRC-1 knockdown also significantly impaired in vivo LTP and disrupted spatial learning and memory. The in vitro results showed that while the expression of synaptic proteins was significantly decreased by SRC-1 knockdown, pCREB expression was also significantly decreased. The above results suggest a pivotal role of SRC-1 in the regulation of hippocampal synaptic plasticity and spatial learning and memory, strongly indicating SRC-1 may serve as a novel therapeutic target for hippocampus-dependent memory disorders.

Orchiectomy and letrozole differentially regulate synaptic plasticity and spatial memory in a manner that is mediated by SRC-1 in the hippocampus of male mice.

Hippocampal synaptic plasticity is the basis of spatial memory and cognition and is strongly regulated by both testicular androgens (testosterone, T) and hippocampal estrogens (17ß-estradiol, E2) converted from T by aromatase, which is inhibited by letrozole (LET), but the contribution of each pathway to spatial memory and the associated mechanisms are unclear. In this study, we first used orchiectomy (ORX) and LET injection to investigate the effects of T and hippocampal E2 on spatial memory and hippocampal synaptic plasticity. Next, we examined the changes in steroid receptors and steroid receptor coactivator-1 (SRC-1) under these treatments. Finally, we constructed an SRC-1 RNA interference lentivirus and an AROM overexpression lentivirus to explore the roles of SRC-1 under T replacement and AROM overexpression. The results revealed spatial memory impairment only after LET. LET induced more actin depolymerization and greater losses of spines, synapses, and postsynaptic proteins compared with ORX. Moreover, although ERα and ERß were affected by LET and ORX at similar levels, AR, GPR30, and SRC-1 were dramatically decreased by LET compared with ORX. Finally, the T and AROM overexpression-induced changes in synaptic proteins and actin polymerization were blocked by SRC-1 inhibition. These results demonstrate that testicular androgens play a limited role, whereas local E2 is more important for cognition, which may explain why castrated men such as eunuchs usually do not have cognitive disorders. These results also suggest a pivotal role of SRC-1 in the action of steroids; thus, SRC-1 may serve as a novel therapeutic target for cognitive disorders.

[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.

Semantic congruent audiovisual integration during the encoding stage of working memory: an ERP and sLORETA study.

Although multisensory integration is an inherent component of functional brain organization, multisensory integration during working memory (WM) has attracted little attention. The present study investigated the neural properties underlying the multisensory integration of WM by comparing semantically related bimodal stimulus presentations with unimodal stimulus presentations and analysing the results using the standardized low-resolution brain electromagnetic tomography (sLORETA) source location approach. The results showed that the memory retrieval reaction times during congruent audiovisual conditions were faster than those during unisensory conditions. Moreover, our findings indicated that the event-related potential (ERP) for simultaneous audiovisual stimuli differed from the ERP for the sum of unisensory constituents during the encoding stage and occurred within a 236-530 ms timeframe over the frontal and parietal-occipital electrodes. The sLORETA images revealed a distributed network of brain areas that participate in the multisensory integration of WM. These results suggested that information inputs from different WM subsystems yielded nonlinear multisensory interactions and became integrated during the encoding stage. The multicomponent model of WM indicates that the central executive could play a critical role in the integration of information from different slave systems.

Catalytic Asymmetric Construction of the Tryptanthrin Skeleton via an Enantioselective Decarboxylative [4 + 2] Cyclization.

The first catalytic asymmetric construction of the tryptanthrin skeleton has been established, taking advantage of a palladium(0)/chiral ligand-catalyzed enantioselective decarboxylative [4 + 2] cyclization of vinyl benzoxazinanones with isatins. This reaction has not only provided a direct and efficient method for constructing chiral tryptanthrin skeleta in high yields and excellent enantioselectivities (up to 97% yield, >99% ee) but also represents the first catalytic asymmetric decarboxylative cyclization of vinyl benzoxazinanones with isatins.