The honeybee is a model organism for studying learning and memory formation and its underlying molecular mechanisms. While DNA methylation is well studied in caste differentiation, its role in learning and memory is not clear in honeybees. Here, we analyzed genome-wide DNA methylation changes during olfactory learning and memory process in A. mellifera using whole genome bisulfite sequencing (WGBS) method. A total of 853 significantly differentially methylated regions (DMRs) and 963 differentially methylated genes (DMGs) were identified. We discovered that 440 DMRs of 648 genes were hypermethylated and 274 DMRs of 336 genes were hypomethylated in trained group compared to untrained group. Of these DMGs, many are critical genes involved in learning and memory, such as Creb, GABA B R and Ip3k, indicating extensive involvement of DNA methylation in honeybee olfactory learning and memory process. Furthermore, key enzymes for histone methylation, RNA editing and miRNA processing also showed methylation changes during this process, implying that DNA methylation can affect learning and memory of honeybees by regulating other epigenetic modification processes.

Most proteins undergo different kinds of modification after translation. Protein acetylation is one of the most crucial post-translational modifications, which causes direct or indirect impact on various biological activities in vivo. As a member of Class III HDACs, SIRT1 was the closest one to the yeast sir2 and drew most attention, while a small number of known SIRT1 substrates caused difficulties to clarify its function. In this work, we designed a novel computational method to screen SIRT1 substrates based on manually collected data and Support Vector Machines (SVMs). Unlike other approaches, we took both primary sequence and protein functional features into consideration. Through integrating functional features, the Matthews correlation coefficient (MCC) for the prediction increased from 0.10 to 0.65. The prediction results were verified by independent dataset and biological experiments. The validation results demostrated that our classifier could effectively identify SIRT1 substrates and filter appropriate candidates for further research. Furthermore, we provide online tool to support SIRT1 substrates prediction, which is freely available at http://bioinfo.bjmu.edu.cn/huac/ .

Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Since autophagy-related genes (ARGs) play a key role in the pathogenesis of many tumors, including ESCC, the purpose of this study is to establish an autophagy-related prognostic risk signature based on ARGs expression profile, and to provide a new method for improving prediction of clinical outcomes. We obtained the expression profiles of ESCC from public data (GSE53625) and extracted the portion of ARGs. Differential expression analysis and enrichment analysis were performed to confirm abnormal autophagy-related biological functions. Univariate and multivariate Cox regression analyses were performed on RNA microarray data (GSE53625) to construct a prognostic risk signature associated with autophagy. The performance of the model was evaluated by receiver operating characteristic (ROC) analysis, survival analysis and Brier score. The model was subjected to bootstrap internal validation. The potential molecular mechanism of gene signature was explored by gene set enrichment analysis (GSEA). Spearman correlation coefficient examined the correlation between risk score and immune status and ferroptosis. The expression levels of genes and proteins were validated by qRT-PCR and immunohistochemistry in ESCC cell lines and ESCC tissues. We constructed and validated an autophagy-related prognostic risk signature in 179 patients with ESCC. The long-term survival of patients in high-risk group was lower than that in low-risk group (log-rank, P value < 0.001). ROC analysis and Brier score confirmed the reliability of the signature. GSEA results showed significant enrichment of cancer- and autophagy-related signaling pathways in the high-risk ESCC patients and immunoregulatory signaling pathways in the low-risk ESCC patients. Correlation analysis showed that the risk signature can effectively predict the effect of immunotherapy. About 33.97% (71/209) ferroptosis-related genes were significantly correlated with risk scores. Finally, the results of qRT-PCR and immunohistochemistry experiments were consistent with bioinformatics analysis. In brief, we constructed a novel autophagy-related gene signature (VIM, UFM1, TSC2, SRC, MEFV, CTTN, CFTR and CDKN1A), which could improve the prediction of clinical outcomes in patients with ESCC.

Reduction and oxidation (redox) reactions occur in living organisms as part of normal cellular metabolism. Here, we established a novel redox-related long non-coding RNAs (rrlncRNAs) signature to predict the prognosis and therapeutic response in Head and neck squamous cell carcinoma (HNSCC). The expression profile and clinical information were obtained from the TCGA project. In total, 10 differently expressed rrlncRNAs associated with prognosis were identified and involved in a prognostic risk score signature by the least absolute shrinkage and selection operator penalized Cox analysis. The area under the receiver operating characteristic curves of the survival rates predicted by the rrlncRNAs signature over one, two, and three years were found to be 0.651, 0.670, and 0.679. Following the completion of the Kaplan-Meier survival study, we discovered that the lower-risk cohort exhibited a much longer overall survival period in contrast with the higher-risk cohort. Univariate and multivariable Cox regression analyses demonstrated that the risk score independently served as a significant predictive factor. GO annotation and KEGG pathway analyses illustrated that the rrlncRNAs signature was strongly associated with immune-related functions as well as signaling pathways. The tumor-infiltrating immune cells, tumor microenvironment, immune-related functions, HLA gene family expression, immune checkpoint genes expression, and somatic variants differed substantially between the low- and high-risk cohorts. Moreover, patients in low-risk group were predicted to present a favorable immunotherapy responsiveness, while in contrast, the high-risk group patients might have a stronger sensitivity to "docetaxel". According to our findings, the rrlncRNAs signature showed an excellent prognosis predictive value and might indicate therapeutic response to immunotherapy in HNSCC.

Facial beauty and moral beauty have been suggested to be two significant forms of social aesthetics. However, it remains unknown the extent to which there are neural underpinnings of the integration of these two forms of beauty. In the present study, participants were asked to make general aesthetic judgments of facial portraits and moral descriptions while collecting fMRI data. The facial portrait and moral description were randomly paired. Neurally, the appreciation of facial beauty and moral beauty recruited a common network involving the middle occipital gyrus (MOG) and medial orbitofrontal cortex (mOFC). The activities of the mOFC varied across aesthetic conditions, while the MOG was specifically activated in the most beautiful condition. In addition, there was a bilateral insular cortex response to ugliness specifically in the congruent aesthetic conditions, while SMA was selectively responsive to the most ugly condition. Activity associated with aesthetic conflict between facial and moral aesthetic information was limited to the medial prefrontal cortex (mPFC), with enhanced response to the incongruent condition compared to the congruent condition. These findings provide novel neural evidence for the integrated aesthetics of social beauty and suggest that integrated aesthetics is a more complex cognitive process than aesthetics restricted to a single modality.

Recent reports suggest that complement system contributes to allograft rejection. However, its underlying mechanism is poorly understood. Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3(-/-)) as skin graft donors or recipients. Compared with C3(+/+) B6 allografts, C3(-/-) B6 grafts dramatically prolonged survival in MHC-II molecule mismatched H-2(bm12) B6 recipients, indicating that C3 plays a critical role in allograft rejection. Compared with C3(+/+) allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mRNA levels were clearly reduced in C3(-/-) allografts. Moreover, C3(-/-) allografts caused attenuated Th1/Th17 responses, but increased CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cell expression markedly in local intragraft and H-2(bm12) recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody (mAb) negated the survival advantages conferred by C3 deficiency. Our results indicate for the first time that C3 deficiency can prolong MHC-II molecule mismatched skin allograft survival, which is further confirmed to be associated with increased CD4(+) CD25(+) Treg cell population expansion and attenuated Th1/Th17 response.

In the last decade, it has been demonstrated that brain functional asymmetry occurs not only in vertebrates but also in invertebrates. However, the mechanisms underlying functional asymmetry remain unclear. In the present study, we trained honeybees of the same parentage and age, on the proboscis extension reflex (PER) paradigm with only one antenna in use. The comparisons of gene expression between the left and right hemispheres were carried out using high throughput sequencing. Our research revealed that gene expression in the honeybee brain is also asymmetric, with more genes having higher expression in the right hemisphere than the left hemisphere. Our studies show that during olfactory learning, the left hemisphere is more responsible for long term memory and the right hemisphere is more responsible for the learning and short term memory.

Retinitis pigmentosa (RP) is highly heterogeneous in both clinical and genetic fields. Accurate mutation screening is very beneficial in improving clinical diagnosis and gene-specific treatment of RP patients. The reason for the difficulties in genetic diagnosis of RP is that the ethnic-specific mutation databases that contain both clinical and genetic information are largely insufficient. In this study, we recruited 98 small Han Chinese families clinically diagnosed as RP, including of 22 dominant, 19 recessive, 52 sporadic, and five X-linked. We then used whole exome sequencing (WES) analysis to detect mutations in the genes known for RP in 101 samples from these 98 families. In total, we identified 57 potential pathogenic mutations in 40 of the 98 (41%) families in 22 known RP genes, including 45 novel mutations. We detected mutations in 13 of the 22 (59%) typical autosomal dominant families, 8 of the 19 (42%) typical autosomal recessive families, 16 of the 52 (31%) sporadic small families, and four of the five (80%) X-linked families. Our results extended the mutation spectrum of known RP genes in Han Chinese, thus making a contribution to RP gene diagnosis and the pathogenetic study of RP genes.

Fibrinogen-like protein 2 (FGL2) is highly expressed in various tumour tissues and plays a vital role in tumour initiation and progression. This study evaluated the clinical significance of FGL2 in patients with clear cell renal cell carcinoma (ccRCC). FGL2 expression in fresh and 170 archived paraffin-embedded ccRCC tissues was measured by quantitative RT-PCR, western blotting, and immunohistochemitry. FGL2 expression was significantly upregulated in ccRCC. Statistical analyses by using Kaplan-Meier method showed that high FGL2 expression was associated with poor overall survival (OS) and recurrence-free survival (RFS) of patients with ccRCC. Multivariate analyses indicated that FGL2 was as an independent prognostic factor of survivaland that tumoural FGL2 levels could significantly predict the prognosis of patients with early-stage ccRCC. Nomogram systems, which integrated FGL2 expression and other clinical parameters, were established and were found to be better than TNM staging in predicting the OS and RFS of patients with ccRCC. FGL2 silencing led to a significant reduction in cells viability and increase in cells apoptosis, accompanied with a reduced ERK1/2 and p38 MAPK activation, in ccRCC cells. Thus, our results suggest that high FGL2 expression is a novel, independent, and an adverse prognostic factor of clinical outcomes in patients with ccRCC.

Hyperuricemia (HUA) endangers human health, and its prevalence has increased rapidly in recent decades. The current study investigated HUA's prevalence and influencing factors in Gongcheng, southern China. A cross-sectional investigation was conducted; 2128 participants aged 30-93 years were included from 2018 to 2019. Univariate and multivariate logistic regression models were used to screen HUA variables. A Bayesian network model was constructed using the PC algorithm to evaluate the association between influencing factors and HUA. The prevalence of HUA was 15.6% (23.2% in men, 10.7% in women). After screening the variables using a logistic regression analysis model, fatty liver disease (FLD), dyslipidemia, abdominal obesity, creatinine (CREA), somatotype, bone mass, drinking, and physical activity level at work were included in the Bayesian network model. The model results showed that dyslipidemia, somatotype, CREA, and drinking were directly related to HUA. Bone mass and FLD were indirectly associated with HUA by affecting the somatotype. The prevalence of HUA in Gongcheng was high in China. The prevalence of HUA was related to somatotype, drinking, bone mass, physical activity level at work, and other metabolic diseases. A good diet and moderate exercise are recommended to maintain a healthy somatotype and reduce the prevalence rate of HUA.

The sex-specific physical and biochemical responses in dioecious plants to abiotic stresses could result in gender imbalance, and how to ease the current situation by microorganisms is still unclear. Using native soil where poplars were grown, growth parameters, soil physicochemical properties in the rhizosphere soil of different sexes of Populus cathayana exposed to salt stress and exogenous arbuscular mycorrhizal (AM) inoculation were tested. Besides, the sex-specific microbial community structures in the rhizosphere soil of different sexes of Populus cathayana were compared under salt stress. To identify the sex-specific microbial community characteristics related to salinity and AM symbiosis, a combined qPCR and DGGE method was used to monitor microbial community diversity. Seedlings suffered severe pressure by salt stress, reflected in limited growth, biomass, and nutrient element accumulation, especially on females. Exogenous AM inoculation treatment alleviated these negative effects, especially under salt treatment of 75 mM. Compared with salt effect, exogenous AM inoculation treatment showed a greater effect on soil physical-chemical properties of both sexes. Based on DGGE results, salt stress negatively affected fungal richness but positively affected fungal Simpson diversity index, while exogenous AM inoculation treatment showed the opposite effect. Structural equation modeling (SEM) was performed to show the causal relationships between salt and exogenous AM inoculation treatments with biomass accumulation and microbial community: salt and exogenous AM inoculation treatment showed complicated effects on elementary concentrations, soil properties, which resulted in different relationship with biomass accumulation and microbial community. Salt stress had a negative effect on soil properties and microbial community structure in the rhizosphere soil of P. cathayana, whereas exogenous AM inoculation showed positive impacts on most of the soil physical-chemical properties and microbial community status.

Survival rate at low temperature becomes a crucial strategy since temperature change often leads to fluctuations in the insect population. Microbes play important roles in the process of resisting low temperature. In this study, we analyzed gut bacterial communities from Chinese white pine beetle Dendroctonus armandi which remained overwintering process under natural conditions from October 2015 to January 2016, monthly, in the Qinling Mountains, Shaanxi, China using Illumina MiSeq sequencing. A total of 835,227 high-quality sequences and 48 singleton operational taxonomic units were obtained. Gut bacterial communities showed variation in relative abundance during the overwintering stage. As ambient temperature declined, Proteobacteria (mostly γ-proteobacteria) became the predominant phylum in the larvae guts, and followed with Actinobacteria and Firmicutes, respectively. In particular, there was no Deinococcus-Thermus in January 2016. Thermoleophilia appeared in November and December 2015, but not for October 2015 and January 2016, nor did δ-proteobacteria. By contrast, gut bacterial community compositions increased in relative abundance in November and December 2015. This study provided initial evidence that gut bacterial communities were associated with the larvae overwintering process at low temperature. Moreover, no complementary studies combining overwintering process of Coleoptera insect and high-throughput sequencing were carried out, paying particular attention to insect in cold season.