Kainate receptors are members of the glutamate receptor family that regulate synaptic function in the brain. They modulate synaptic transmission and the excitability of neurons; however, their contributions to neural circuits that underlie behavior are unclear. To understand the net impact of kainate receptor signaling, we generated knockout mice in which all five kainate receptor subunits were ablated (5ko). These mice displayed compulsive and perseverative behaviors, including over-grooming, as well as motor problems, indicative of alterations in striatal circuits. There were deficits in corticostriatal input to spiny projection neurons (SPNs) in the dorsal striatum and correlated reductions in spine density. The behavioral alterations were not present in mice only lacking the primary receptor subunit expressed in adult striatum (GluK2 KO), suggesting that signaling through multiple receptor types is required for proper striatal function. This demonstrates that alterations in striatal function dominate the behavioral phenotype in mice without kainate receptors.

Febrile seizures (FSs) are common neurological disorders in both infants and children, although the precise underlying mechanism remains to be explored, especially in the expression pattern and function of microRNAs (miRNAs). In this report, we aimed to screen new potential miRNAs and examine the role of miR-148a-3p in hippocampal neurons in FS rats via Synaptojanin-1 (SYNJ1). Thirty rats were randomly divided into the normal and FS model groups, which were investigated by miRNA array. This process identified 31 differentially expressed (20 upregulated and 11 downregulated) miRNAs and potential miRNA target genes. In addition, hippocampal neurons were assigned into five groups for different transfections. Apoptosis was detected by TUNEL and flow cytometry. SYNJ1 was identified as a target gene of miR-148-3p. In vitro experiments revealed that inhibition of miR-148a-3p decreased neuronal cell apoptosis. Moreover, overexpression of miR-148a-3p resulted in activation of PI3K/Akt signaling pathway and the apoptosis of hippocampal neurons. MiR-148a-3p inhibitor could reverse the above events. Taken together, our data demonstrated that the hippocampal miRNA expression profiles of a rat model of FS provide a large database of candidate miRNAs and neuron-related target genes. Furthermore, miR-148a-3p acted as a apoptosis enhcaner via the activation of the SYNJ1/PI3K/Akt signaling pathway, highlighting a potential therapeutic target in the treatment of infants with hyperthermia-induced brain injury.

Corydalis yanhusuo W.T. Wang is a classic herb that is frequently used in traditional Chinese medicine and is efficacious in promoting blood circulation, enhancing energy, and relieving pain. Benzylisoquinoline alkaloids (BIAs) are the main bioactive ingredients in Corydalis yanhusuo. However, few studies have investigated the BIA biosynthetic pathway in C. yanhusuo, and the biosynthetic pathway of species-specific chemicals such as tetrahydropalmatine remains unclear. We performed full-length transcriptomic and metabolomic analyses to identify candidate genes that might be involved in BIA biosynthesis and identified a total of 101 full-length transcripts and 19 metabolites involved in the BIA biosynthetic pathway. Moreover, the contents of 19 representative BIAs in C. yanhusuo were quantified by classical targeted metabolomic approaches. Their accumulation in the tuber was consistent with the expression patterns of identified BIA biosynthetic genes in tubers and leaves, which reinforces the validity and reliability of the analyses. Full-length genes with similar expression or enrichment patterns were identified, and a complete BIA biosynthesis pathway in C. yanhusuo was constructed according to these findings. Phylogenetic analysis revealed a total of ten enzymes that may possess columbamine-O-methyltransferase activity, which is the final step for tetrahydropalmatine synthesis. Our results span the whole BIA biosynthetic pathway in C. yanhusuo. Our full-length transcriptomic data will enable further molecular cloning of enzymes and activity validation studies.

Cnaphalocrocis medinalis granulovirus (CnmeGV) is a potential microbial agent against the rice leaffolder. Innate immunity is essential for insects to survive pathogenic infection. Therefore, to clarify the immune response of Cnaphalocrocis medinalis to the viral colonization, the gene expression profile of C. medinalis infected with CnmeGV was constructed by RNA-seq. A total of 8,503 differentially expressed genes (DEGs) were found including 5,304 up-regulated and 3,199 down-regulated unigenes. Gene enrichment analysis indicated that these DEGs were mainly linked to protein synthesis and metabolic process as well as ribosome and virus-infection pathways. Specifically, a significantly up-regulated PiggyBac-like transposon gene was identified suggested that the enhancement of transposon activity is related to host immunity. Further, the DEGs encoding oxidative stress related genes were identified and validated by RT-qPCR. Overall, 9 antioxidant enzyme genes and 4 antioxidant protein genes were up-regulated, and the extensive glutathione S-transferase genes were down-regulated. Our results provide a basis for understanding the molecular mechanisms of baculovirus action and oxidative stress response in C. medinalis and other insects.

Rapid climate change has wide-ranging implications for the Arctic region, including sea ice loss, increased geopolitical attention, and expanding economic activity resulting in a dramatic increase in shipping activity. As a result, the risk of harmful non-native marine species being introduced into this critical region will increase unless policy and management steps are implemented in response. Using data about shipping, ecoregions, and environmental conditions, we leverage network analysis and data mining techniques to assess, visualize, and project ballast water-mediated species introductions into the Arctic and dispersal of non-native species within the Arctic. We first identify high-risk connections between the Arctic and non-Arctic ports that could be sources of non-native species over 15 years (1997-2012) and observe the emergence of shipping hubs in the Arctic where the cumulative risk of non-native species introduction is increasing. We then consider how environmental conditions can constrain this Arctic introduction network for species with different physiological limits, thus providing a tool that will allow decision-makers to evaluate the relative risk of different shipping routes. Next, we focus on within-Arctic ballast-mediated species dispersal where we use higher-order network analysis to identify critical shipping routes that may facilitate species dispersal within the Arctic. The risk assessment and projection framework we propose could inform risk-based assessment and management of ship-borne invasive species in the Arctic.

Despite recent progress in hepatitis treatment, there have been no significant advances in the development of liver cancer vaccines in recent years. In this study, we investigated the regulatory effect and potential mechanism of hepatocyte growth factor receptor (MET, also known as HGFR) on tumor vaccinations for liver cancer in mice. Herein, we demonstrate that MET expression is significantly associated with the immunogenicity of liver cancer in mice and humans, and that MET depletion dramatically enhances the protective efficacy of chemotherapy-based anti-liver cancer vaccination. Mechanistically, MET repressed liver cancer immunogenicity independent of the traditional PI3K-AKT cascade, and MET interacted with vacuolar ATP synthase (V-ATPase) and mediated the activation of mammalian target of rapamycin (MTOR), thus suppressing liver cancer immunogenicity. The efficacy of chemotherapy-based liver cancer vaccination was markedly enhanced by targeting the MET-V-ATPase-MTOR axis, highlighting a translational strategy for identifying MET-associated drug candidates for cancer prevention.

Phthalate ester plasticizers are used to improve the plasticity and strength of plastics. One of the most widely used and studied, di-2-ethylhexyl phthalate (DEHP), has been labeled as an endocrine disruptor. The major and toxic metabolic derivative of DEHP, mono-2-ethylhexyl phthalate (MEHP), is capable of interfering with mitochondrial function, but its mechanism of action on mitophagy remains elusive. Here, we report that MEHP exacerbates cytotoxicity by amplifying the PINK1-Parkin-mediated mitophagy pathway. First, MEHP exacerbated mitochondrial damage induced by low-dose CCCP via increased reactive oxygen species (ROS) production, decreased mitochondrial membrane potential (MMP), and enhanced fragmentation in mitochondria. Second, co-exposure to MEHP and CCCP ("MEHP-CCCP") induced robust mitophagy. Mechanistically, MEHP-CCCP stabilized PINK1, increased the level of phosphorylated ubiquitin (pSer 65-Ub), and led to Parkin mitochondrial translocation and activation. Third, MEHP-CCCP synergistically caused more cell death, while inhibition of mitophagy, either through chemical or gene silencing, reduced cell death. Finally and importantly, co-treatment with N-acetyl cysteine (NAC) completely counteracted the effects of MEHP-CCCP, suggesting that mitochondrial ROS played a vital role in this process. Our results link mitophagy and MEHP cytotoxicity, providing an insight into the potential roles of endocrine disrupting chemicals (EDCs) in human diseases such as Parkinson's disease.

Changing functionalities of materials using simple methods is an active area of research, as it is "green" and lowers the developing cost of new products for the enterprises. A new small molecule racemic N,N-dimethyl aspartic acid has been prepared. Its structure is determined by single-crystal X-ray diffraction. It is characterized by FTIR, XPS, 1H NMR, and mass spectroscopy. Its near-infrared luminescence can be enhanced by the combination of metal ions, including Dy3+, Gd3+, Nd3+, Er3+, Sr3+, Y3+, Zn2+, Zr4+, Ho3+, Yb3+, La3+, Pr6+/Pr3+, and Sm3+ ions. An optical chemistry mechanism upon interaction between the sensitizer and activator is proposed. Furthermore, the association of Ca2+, Sr2+, or Zr4+ ions to the molecule enhanced its photodegradation for dyes under white-light irradiation. Specifically, rhodamine 6G can be degraded by the Ca2+-modified molecule; rhodamine B, rhodamine 6G, and fluorescein sodium salt can be degraded by the Sr2+- or Zr4+-modified molecule. This surprising development opens a way in simultaneously increasing NIR luminescence and the ability of dye photodegradation for the investigated molecule.

Long non‑coding RNA (lncRNA) LINC00473 plays a carcinogenic role in a variety of different tumor types. Nevertheless, the mechanisms through which LINC00473 regulates the radiosensitivity of esophageal squamous cell carcinoma (ESCC) cells remains elusive. In the present study, reverse transcription‑quantitative PCR was used to quantify the expression of LINC00473, microRNA (miRNA/miR)‑497‑5p and cell division cycle 25A (CDC25A) in ESCC tissues. The association between LINC00473 expression and the clinicopathological characteristics of patients with ESCC was also assessed. Furthermore, Cell Counting kit‑8 and colony formation assays were carried out to monitor the proliferation of ESCC cells exposed to X‑ray radiation. A dual‑luciferase reporter assay was also conducted to analyze the interaction between LINC00473 and miR‑497‑5p, as well as the interaction between CDC25A and miR‑497‑5p. The findings of the present study demonstrated that in ESCC tissues and cells, the expression levels of LINC00473 and CDC25A were significantly upregulated, while the expression of miR‑497‑5p was downregulated. The high expression level of LINC00473 was associated with a higher T stage, lymph node metastasis stage and a lower tumor differentiation grade in patients with ESCC. Following irradiation, transfection with miR‑497‑5p mimics reduced the promoting effect of LINC00473 overexpression on ESCC cell proliferation, and partially impeded the resistance of ESCC cells to X‑ray radiation induced by LINC00473 overexpression. Moreover, transfection with miR‑497‑5p inhibitors partially alleviated the inhibitory effects of LINC00473 knockdown on cellular proliferation, and partly reversed the sensitivity of cells to X‑ray irradiation induced by LINC00473 knockdown. Furthermore, it was confirmed that miR‑497‑5p was able to bind LINC00473 and the 3'‑untranslated region of CDC25A. On the whole, the findings of the present study demonstrate that LINC00473 reduces the radiosensitivity of ESCC cells by modulating the miR‑497‑5p/CDC25A axis.

Solitary fibrous tumor (SFT) is an uncommon mesenchymal tumor that is most common in the pleura. However, according to previous studies, the SFT of the pancreas is extremely rare; only 20 cases have been reported so far. Here, we conduct a literature review and report the first case of atypical/malignant SFT of the pancreas with spleen vein invasion.

The aim of the study was to assess the clinico-pathological features and prognosis of mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRC) in young colorectal cancer (CRC) patients.

To investigate the effect of recombinant adenovirus-mediated HIF-1 alpha (HIF-1α) on the expression of vascular endothelial growth factor (VEGFA) and HIF-1α in hypoxic brain microvascular endothelial cells (BMEC) in rats.

Recent studies have shown that MDR could be induced by the high stemness of cancer cells. In a previous study, we found bufalin could reverse MDR and inhibit cancer cell stemness in colorectal cancer, but the relationship between them was unclear. Here we identified overexpressing CD133 increases levels of Akt/nuclear factor-κB signaling mediators and MDR1, while increasing cell chemoresistance. Furthermore, bufalin reverses colorectal cancer MDR by regulating cancer cell stemness through the CD133/nuclear factor-κB/MDR1 pathway in vitro and in vivo. Taken together, our results suggest that bufalin could be developed as a novel 2-pronged drug that targets CD133 and MDR1 to eradicate MDR cells and could ultimately be combined with conventional chemotherapeutic agents to improve treatment outcomes for patients with colorectal cancer.

Background: Pancreatic cancer (PC) is a highly malignant tumor with no effective early diagnostic biomarkers. This study was performed to screen and identify serum microRNAs (miRNAs) as noninvasive biomarkers for PC diagnosis. Methods: Two upregulated miRNAs were selected by integrated analysis of three independent GEO datasets. Then, the expressions of two miRNAs in serum were determined by quantitative reverse-transcription PCR among 120 PC patients, 40 benign disease controls and 40 healthy controls. The correlation between serum miRNAs and clinical characteristics was analyzed. The diagnostic utility of miRNAs was compared to CA19-9 using receiver operating characteristic curve analysis. Results: We discovered miR-1290 and miR-1246 were upregulated in PC patients through GEO datasets analysis. Serum miR-1290 and miR-1246 expression levels were elevated in PC patients compared to all controls and dramatically decreased after tumor resection (all P<0.001). The area under the curve (AUC) for miR-1290 was larger than miR-1246 and CA19-9 (miR-1290: 0.91; miR-1246: 0.81; CA19-9: 0.82). The combined diagnosis of individual or both miRNAs with CA19-9 was more effective for discriminating PC from all controls than the single CA19-9 assay (miR-1290+CA19-9: 0.96, miR-1246+CA19-9: 0.93, miR-1290+miR-1246+CA19-9: 0.97). The abundance of serum miR-1290 and miR-1246 was associated with tumor stage and size respectively and logistic modeling proved that both of them were independent risk factors for PC. Conclusion: Serum miR-1290 and miR-1246 might be promising biomarkers for PC diagnosis and the combined detection of CA19-9, together with miR-1290 or miR-1246, could improve the diagnostic accuracy of PC.

Marek's disease virus (MDV), an alpha herpes virus, causes a lymphoproliferative state in chickens known as Marek's disease (MD), resulting in severe monetary losses to the poultry industry. Because lymphocytes of bursa of Fabricius and spleen are prime targets of MDV replication during the early cytolytic phase of infection, the immune response in bursa and spleen should be the foundation of late immunity induced by MDV. However, the mechanism of the MDV-mediated host immune response in lymphocytes in the early stage is poorly understood. The present study is primarily aimed at identifying the crucial genes and significant pathways involved in the immune response of chickens infected with MDV CVI988 and the very virulent RB1B (vvRB1B) strains. Using the RNA sequencing approach, we analyzed the generated transcriptomes from lymphocytes isolated from chicken bursa and spleen. Our findings validated the expression of previously characterized genes; however, they also revealed the expression of novel genes during the MDV-mediated immune response. The results showed that after challenge with CVI988 or vvRB1B strains, 634 and 313 differentially expressed genes (DEGs) were identified in splenic lymphocytes, respectively. However, 58 and 47 DEGs were observed in bursal lymphocytes infected with CVI988 and vvRB1B strains, respectively. Following MDV CVI988 or vvRB1B challenge, the bursal lymphocytes displayed changes in IL-6 and IL-4 gene expression. Surprisingly, splenic lymphocytes exhibited an overwhelming alteration in the expression of cytokines and cytokine receptors involved in immune response signaling. On the other hand, there was no distinct trend between infection with CVI988 and vvRB1B and the expression of cytokines and chemokines, such as IL-10, IFN-γ, STAT1, IRF1, CCL19, and CCL26. However, the expression profiles of IL-1β, IL-6, IL8L1, CCL4 (GGCL1), and CCL5 were significantly upregulated in splenic lymphocytes from chickens infected with CVI988 compared with those of chickens infected with vvRB1B. Because these cytokines and chemokines are considered to be associated with B cell activation and antigenic signal transduction to T cells, they may indicate differences of immune responses initiated by vaccinal and virulent strains during the early phase of infection. Collectively, our study provides valuable data on the transcriptional landscape using high-throughput sequencing to understand the different mechanism between vaccine-mediated protection and pathogenesis of virulent MDV in vivo.

This study aimed to investigate the role of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor(R) signaling in the regulation of seizure susceptibility and to explore the potential mechanism in rats.

Various salmonid species are cultivated in cold water aquaculture. However, due to limited genomic data resources, specific high-throughput genotyping tools are not available to many of the salmonid species. In this study, a 57K single nucleotide polymorphism (SNP) array for rainbow trout (Oncorhynchus mykiss) was utilized to detect polymorphisms in seven salmonid species, including Hucho taimen, Oncorhynchus masou, Salvelinus fontinalis, Brachymystax lenok, Salvelinus leucomaenis, O. kisutch, and O. mykiss. The number of polymorphic markers per population ranged from 3,844 (O. kisutch) to 53,734 (O. mykiss), indicating that the rainbow trout SNP array was applicable as a universal genotyping tool for other salmonid species. Among the six other salmonid populations from four genera, 28,882 SNPs were shared, whereas 525 SNPs were polymorphic in all four genera. The genetic diversity and population relationships of the seven salmonid species were studied by principal component analysis (PCA). The phylogenetic relationships among populations were analyzed using the maximum likelihood method, which indicated that the shared SNP markers provide reliable genomic information for population genetic analyses in common aquaculture salmonid fishes. Furthermore, this obtained genomic information may be applicable for population genetic evaluation, marker-assisted breeding, and propagative parent selection in fry production.

Meloidogyne incognita is a devastating nematode that causes significant losses in cucumber production worldwide. Although numerous studies have emphasized on the susceptible response of plants after nematode infection, the exact regulation mechanism of M. incognita-resistance in cucumber remains elusive. Verification of an introgression line, 'IL10-1', with M. incognita-resistance provides the opportunity to unravel the resistance mechanism of cucumber against M. incognita.

The present study investigated test-taking motivation in L2 listening testing context by applying Expectancy-Value Theory as the framework. Specifically, this study was intended to examine the complex relationships among expectancy, importance, interest, listening anxiety, listening metacognitive awareness, and listening test score using data from a large-scale and high-stakes language test among Chinese first-year undergraduates. Structural equation modeling was used to examine the mediating effect of listening metacognitive awareness on the relationship between expectancy, importance, interest, listening anxiety, and listening test score. According to the results, test takers' listening scores can be predicted by expectancy, interest, and listening anxiety significantly. The relationship between expectancy, interest, listening anxiety, and listening test score was mediated by listening metacognitive awareness. The findings have implications for test takers to improve their test taking motivation and listening metacognitive awareness, as well as for L2 teachers to intervene in L2 listening classrooms.

Src homology 2 containing protein tyrosine phosphatase (PTP) 2 (Shp2) is a typical tyrosine phosphatase interacting with receptor tyrosine kinase to regulate multiple signaling pathways in diverse pathological processes. Here, we will investigate the effect of Shp2 inhibition on pulmonary arterial hypertension (PAH) in a rat model and its potential cellular and molecular mechanisms underlying.