Integrative Analysis of Morphine-Induced Differential Circular RNAs and ceRNA Networks in the Medial Prefrontal Cortex.

Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Despite the fact that the functional mechanisms of most circRNAs remain unknown, emerging evidence indicates that circRNAs could sponge microRNAs (miRNAs), bind to RNA binding proteins (RBP), and even be translated into protein. Recent research has demonstrated the crucial roles played by circRNAs in neuropsychiatric disorders. The medial prefrontal cortex (mPFC) is a crucial component of drug reward circuitry and exerts top-down control over cognitive functions. However, there is currently limited knowledge about the correlation between circRNAs and morphine-associated contextual memory in the mPFC. Here, we performed morphine-induced conditioned place preference (CPP) in mice and extracted mPFC tissue for RNA-sequencing. Our study represented the first attempt to identify differentially expressed circRNAs (DEcircRNAs) and mRNAs (DEmRNAs) in the mPFC after morphine-induced CPP. We identified 47 significantly up-regulated DEcircRNAs and 429 significantly up-regulated DEmRNAs, along with 74 significantly down-regulated DEcircRNAs and 391 significantly down-regulated DEmRNAs. Functional analysis revealed that both DEcircRNAs and DEmRNAs were closely associated with neuroplasticity. To further validate the DEcircRNAs, we conducted qRT-PCR, Sanger sequencing, and RNase R digestion assays. Additionally, using an integrated bioinformatics approach, we constructed ceRNA networks and identified critical circRNA/miRNA/mRNA axes that contributed to the development of morphine-associated contextual memory. In summary, our study provided novel insights into the role of circRNAs in drug-related memory, specifically from the perspective of ceRNAs.

Environmental cue difference and training duration modulate spatial learning and cue preference in detour task.

In this study, we investigated how different environmental cue and the proficiency of body motion influenced detour learning behaviour and cue preference in cue conflict situations. Domestic chicks were trained to detour around an obstacle and follow a fixed route to rejoin with their partners. When the environmental cue was red versus blue vertical stripes, the chicks learned the detour task quicker, and as the number of training trials after route acquisition increased, they switched their preference from the environmental cue to a body-motion cue in the cue conflict test. On the other hand, when the environmental cue was vertical versus horizontal blue stripes, the chicks learned the detour task slower and showed a dependence on the body-motion cue regardless of the number of training trials performed after route acquisition. When the environmental cue was removed, most chicks could still successfully detour according to the specific route on which they had been trained. Furthermore, a significant difference in detour latency was found between chicks using the environmental cue and chicks using the body-motion cue, suggesting separate neuronal circuits responsible for processing the two types of information. Our results demonstrated that young domestic chicks could use both environmental cue and body-motion cues to memorize the route during the detour learning task; however, the detour route preference could be dynamically modulated by difference of the environmental cue and the number of training trials they received.

Pregnancy-associated plasma protein-A (PAPPA) promotes breast cancer progression.

Breast cancer is the most common malignancy in females and poses a significant health threat to women. Pregnancy-associated plasma protein-A (PAPPA) is highly expressed in pregnancy-associated breast cancer (PABC) tissues. In this study, we investigated the functional role of PAPPA in regulating the malignant phenotype of breast cancer. We first examined the expression level of PAPPA in PABC tissue and breast cancer cell lines using quantitative real-time polymerase-chain reaction (qRT-PCR) and western blot. Next, the functional role of PAPPA in breast cancer cells was validated by overexpression and knockdown experiments. Cell counting kit-8 (CCK-8) proliferation assay, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, wound healing and transwell invasion assay were used to examine cell proliferation, migration, and invasion ability. We further identified the microRNA target regulating PAPPA and studied its functional role. Finally, we examined the impact of PAPPA on the tumorigenesis and metastasis of breast cancer in mice model. Our study revealed that PAPPA was upregulated in PABC tissues and breast cancer cells. Overexpression of PAPPA promoted cell proliferation, motility, invasion, and epithelial-mesenchymal transition (EMT). We further identified miR-497-5p as a negative regulator of PAPPA, which suppressed cell proliferation, migration, invasion, and EMT in breast cancer cells. We also validated the oncogenic role of PAPPA in the mouse xenograft model. Collectively, our study suggests that PAPPA is an oncogenic protein highly expressed in PABC tissues and promotes breast cancer progression, which could serve as a novel therapeutic target for breast cancer.

Development and Validation of an Immune-Related Gene Pair Signature in Skin Cutaneous Melanoma.

INTRODUCTION: Skin cutaneous melanoma (SKCM) is a common skin malignancy worldwide, and its metastasis and mortality rates are high. The molecular characteristics exhibited by tumor-immune interactions have drawn the attention from researchers. Therefore, increased knowledge and new strategies to identify effective immune-related biomarkers may improve the clinical management of SKCM by providing more accurate prognostic information. PATIENTS AND METHODS: In this study, we established a prognostic immune-related gene pair (IRGP) signature for predicting the survival of SKCM patients. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided gene expression profiles together with clinical information, and the samples were randomly divided into three groups including the training, testing, and validation datasets. The regression model of least absolute shrinkage and selection operator (LASSO) helped to identify a 13-IRGP signature with a significant relation to the survival of SKCM patients. RESULTS: The training, TCGA, and independent sets have an average value of area under the curve of 0.79, 0.76, and 0.82, respectively. In addition, this 13-IRGP signature can noticeably divide SKCM patients into high-risk group and low-risk group with significantly different prognoses. Many biological activities such as gene family were enriched among the genes in our IRGP signature. While analyzing the risk signature and clinical characteristics, there was a large difference in the risk score between T stage and tumor stage grouping. Finally, we constructed a nomogram and forest plots of the risk score and clinical features. CONCLUSION: In summary, we developed a robust 13-IRGP prognostic signature in SKCM, which can identify and provide new insights into immunological biomarkers.

WITHDRAWN: Resveratrol partially prevents learning and memory deficits in rats exposed to gaseous formaldehyde.

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Allele frequencies of 20 autosomal STR loci for 207 unrelated individuals of the Blang people in China.

The Blang is a minority living in the mountainous areas of Xishuangbanna Dai Autonomous Prefecture, and they also scatter in the neighboring cities of Lincang and Simao. This population is investigated in this study through PowerPlex® 21 System. The frequency distribution of allele, forensic, and population parameters of 20 autosomal short tandem repeat loci were evaluated based on 207 non-related individuals from Blang minority; meanwhile, the genetic relationships between Blang and 11 related populations were also assessed.

Paternal Y chromosomal genotyping reveals multiple large-scale admixtures in the formation of Lolo-Burmese-speaking populations in southwest China.

Background: Bai and Yi people are two Tibeto-Burman speaking ethnic groups in Yunnan, southwest China. The genetic structure and history of these two groups are largely unknown due to a lack of available genetic data.Aim: To investigate the paternal genetic structure and population relationship of the Yi and Bai people.Subjects and methods: We collected samples from 278 Bai individuals and 283 Yi individuals from Yunnan and subsequently genotyped 43 phylogenetically relevant Y-SNPs in those samples. We estimated haplogroup frequencies and merged our data with a reference database including 46 representative worldwide populations to infer genetic relationships.Results: Y chromosomal haplogroup O-M175 is the dominant lineage in both Bai and Yi people. The Bai and Yi show a close genetic relationship with other Tibeto-Burman-speaking populations with high frequencies of haplogroup O2a2b1a1-Page23, which is also confirmed by PCA. The frequencies of the Tai-Kadai specific lineage O1a-M119, the southern China widespread lineage O1b-P31 and the eastern China enriched lineage O2a1b-002611, are also relatively high in our studied populations.Conclusions: The paternal Y chromosomal affinity of the Bai and Yi with Tibeto-Burman groups is consistent with the language classification. During the formation of the Bai and Yi populations, there were multiple large-scale admixtures, including the expansion of Neolithic farming populations from northern China, the assimilation of Tai-Kadai-speaking populations in southwest China, the demographic expansion driven by Neolithic agricultural revolution from southern China, and the admixture with populations of military immigration from northern and eastern China.

Age estimation using pulp/enamel volume ratio of impacted mandibular third molars measured on CBCT images in a northern Chinese population.

The present study aims to evaluate the relation between chronological age and the ratio of pulp volume (PV) to enamel volume (EV) of impacted mandibular third molars (IMTMs) by using cone-beam computed tomography (CBCT) images and an improved 3D image segmentation technique. A sample of CBCT images of IMTM was collected from 414 northern Chinese subjects (214 male and 200 female clinical patients) ranging in age from 20 to 65 years. The GrowCut effect image segmentation (GCEIS) module algorithm was used to calculate the PV and EV from CBCT images. The total sample was divided into a training group and validation group in a ratio of 7 to 3. The PV/EV ratio (PEr) in the training sample was used to develop a mathematical formula for age estimation as follows: age = - 5.817-21.726 × Ln PEr (p < 0.0001) (Ln, natural logarithm). The mean absolute error (MAE) and root mean square error (RMSE) were used to determine the precision and accuracy of the mathematical formula in the validation group and all samples. The MAEs in the male, female, and pooled gender samples were 9.223, 7.722, and 8.41, respectively, and the RMSEs in the male, female, and pooled gender samples were 10.76, 9.58, and 9.986, respectively. The precise and accurate results indicate that the PEr of IMTM in CBCT images is a potential index for dental age estimation and is possible to be used in forensic medicine.

Allele frequency of 19 autosomal STR loci in the Bai population from the southwestern region of mainland China.

The aim of this study was to investigate a 19 STR loci database using the Bai population from China. This multiplex amplification kit included 13 CODIS STR markers and six plus STR markers (D19S433, Penta E, D2S1338, Penta D, D6S1043, and D12S391) that were successfully analyzed by using 1158 DNA samples from the Bai population from the southwestern part of mainland China. These results indicate that this multiplex amplification kit may provide significant polymorphic information for kinship testing and relationship investigations.