The Structure, Biology, and Mechanical Function of Tendon/Ligament-Bone Interfaces.

After tendon or ligament reconstruction, the interface between the hard bone and soft connective tissue is considerably weakened and is difficult to restore through healing. The tendon/ligament-bone interface is mechanically the weakest point under tensile loading and is often the source of various postoperative complications, such as bone resorption and graft laxity. A comprehensive understanding of the macro- and microfeatures of the native tendon/ligament-bone interface would be beneficial for developing strategies for regenerating the tissue. This article discusses the structural, biological, and mechanical features of the tendon/ligament-bone interfaces and how these can be affected by aging and loading conditions.

A pleiotropic role of sialidase in the pathogenicity of Porphyromonas gingivalis.

As one of the keystone pathogens of periodontitis, the oral bacterium Porphyromonas gingivalis produces an array of virulence factors, including a recently identified sialidase (PG0352). Our previous report involving loss-of-function studies indicated that PG0352 plays an important role in the pathophysiology of P. gingivalis. However, this report had not been corroborated by gain-of-function studies or substantiated in different P. gingivalis strains. To fill these gaps, herein we first confirm the role of PG0352 in cell surface structures (e.g., capsule) and serum resistance using P. gingivalis W83 strain through genetic complementation and then recapitulate these studies using P. gingivalis ATCC33277 strain. We further investigate the role of PG0352 and its counterpart (PGN1608) in ATCC33277 in cell growth, biofilm formation, neutrophil killing, cell invasion, and P. gingivalis-induced inflammation. Our results indicate that PG0352 and PGN1608 are implicated in P. gingivalis cell surface structures, hydrophobicity, biofilm formation, resistance to complement and neutrophil killing, and host immune responses. Possible molecular mechanisms involved are also discussed. In summary, this report underscores the importance of sialidases in the pathophysiology of P. gingivalis and opens an avenue to elucidate their underlying molecular mechanisms.

MBD3 promotes epithelial-mesenchymal transition in gastric cancer cells by upregulating ACTG1 via the PI3K/AKT pathway.

BACKGROUND: Gastric cancer (GC) is a common malignancy and a leading cause of cancer-related death with high morbidity and mortality. Methyl-CpG binding domain protein 3 (MBD3), a key epigenetic regulator, is abnormally expressed in several cancers, participating in progression and metastasis. However, the role of MBD3 in GC remains unknown. METHODS: MBD3 expression was assessed via public databases and validated by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). The prognosis of MBD3 was analysed via bioinformatics based on the TCGA dataset. The migration, invasion and proliferation of GC cells were examined by transwell, wound healing, cell counting kit (CCK)-8, colony-formation and xenograft mouse models. Epithelial-mesenchymal transition (EMT) and phosphatidylinositide 3-kinases/ protein Kinase B (PI3K/AKT) pathway markers were evaluated by Western blotting. RNA sequencing was used to identify the target of MBD3. RESULTS: MBD3 expression was higher in GC tissues and cells than in normal tissues and cells. Additionally, high MBD3 levels were associated with poor prognosis in GC patients. Subsequently, we proved that MBD3 enhanced the migration, invasion and proliferation abilities of GC cells. Moreover, western blot results showed that MBD3 promoted EMT and activated the PI3K/AKT pathway. RNA sequencing analysis showed that MBD3 may increase actin γ1 (ACTG1) expression to promote migration and proliferation in GC cells. CONCLUSION: MBD3 promoted migration, invasion, proliferation and EMT by upregulating ACTG1 via PI3K/AKT signaling activation in GC cells and may be a potential diagnostic and prognostic target.

Pan-Cancer Analysis Reveals SOX2 as a Promising Prognostic and Immunotherapeutic Biomarker Across Various Cancer Types, Including Pancreatic Cancer.

SOX2 is associated with the initiation, growth, and progression of various tumors and is related to stem cells. However, further studies of SOX2 in a pan-cancer context are warranted. In this study, we obtained pan-cancer and clinical data from TCGA, GTEx, STRING, and TISIDB databases and we analyzed the relationship between SOX2 expression levels and changes in gene diagnostics and survival prognosis. Additionally, we compared the expression levels of SOX2 in pancreatic cancer and healthy pancreatic tissues using Wilcoxon's rank-sum test. Functional enrichment analysis was conducted to identify potential signaling pathways and biological functions. To determine the prognostic value, we used the area under the curve (AUC) and Cox regression analysis. We further developed nomograms to predict overall survival at 1, 6, and 12 months after cancer diagnosis. Moreover, we assessed immune cell infiltration using single-sample gene set enrichment analysis. The methylation status of SOX2 was analyzed using the UALCAN and MethSurv databases. Furthermore, we verified the differential expression of SOX2 in pancreatic cancer cell lines by western blotting and quantitative polymerase chain reaction. We also confirmed the effect of SOX2 on the invasion and migration of pancreatic cancer cells using transwell and scratch assays. The biological effects were confirmed using a clone-formation assay. Our findings suggest that SOX2 is highly expressed in various tumor tissues and has potential clinical significance. It can be used as a new biomarker for pancreatic adenocarcinoma and plays a crucial role in immune infiltration.

Transcriptome sequencing of circular RNA reveals the involvement of hsa-SCMH1_0001 in the pathogenesis of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease. Exosomes are endosome-derived extracellular vesicles that can take part in intercellular communication. Circular RNAs (circRNAs) are noncoding RNAs characterized by covalently closed-loop structures, which perform a crucial function in many diseases. AIM: To clarify the expression and function of exosomal circRNSs of PD patients and look for circRNAs that might be related to the pathogenesis of PD. MATERIALS AND METHODS: We examined circRNA and mRNA expression profiles in peripheral exosomes from PD patients (n = 23) and healthy controls (n = 15) using next-generation sequencing (NGS) technology, functional annotation, and quantitative polymerase chain reaction. Correlation analysis was performed between the expression levels of the circRNAs and the clinical characteristics of PD patients. The binding miRNAs and target genes were predicted using TargetScanHuman, miRDB, and miRTarBase. The predicted target genes were compared with the differentially expressed mRNAs in sequencing results. RESULTS: According to the NGS, 62 upregulated and 37 downregulated circRNAs in the PD group were screened out. Correlation analysis revealed that hsa-SCMH1_0001 has strong clinical relevance. We identified 17 potential binding miRNAs of hsa-SCMH1_0001 with 149 potential target genes. ARID1A and C1orf115 belong to the intersection of the predicted target genes and the differentially expressed mRNAs obtained by sequencing. CONCLUSION: This study suggested that hsa-SCMH1_0001 and its target genes ARID1A and C1orf115 are downregulated in PD patients and may be involved in the occurrence of PD.

CTSK and PLAU as Prognostic Biomarker and Related to Immune Infiltration in Pancreatic Cancer: Evidence from Bioinformatics Analysis and qPCR.

Pancreatic adenocarcinoma (PAAD) is a malignancy with the highest mortality rate worldwide. There is a pressing need for novel biomarkers that can facilitate early detection and serve as targets for therapeutic interventions beyond the commonly utilized CA199 marker. This study utilized microarray datasets (GSE15471, GSE62165, and GSE28735) from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) and construct a protein-protein interaction network using STRING and Cytoscape. Hub genes were selected using BiNGO. Expression profiles and clinical data from the Cancer Genome Atlas (TCGA) were then used to compare the expression levels of CTSK and PLAU in pancreatic cancer and healthy pancreatic tissues via the Wilcoxon rank-sum test, with further validation using qPCR. Functional enrichment analysis was conducted to explore potential signaling pathways and biological functions. Prognostic values were assessed by the Kaplan-Meier and Cox regression analyses, and an overall survival (OS) nomogram was created to predict 1-, 2-, and 3-year survival after cancer diagnosis. The infiltration of immune cells was evaluated by single-sample gene set enrichment analysis. The methylation status of both genes was analyzed using the UALCAN and MethSurv databases. The results demonstrated that CTSK and PLAU were overexpressed in pancreatic cancer and that the hypomethylation status of both genes was associated with a poor prognosis. The overexpression of both genes was positively correlated with various immune cells, and functional enrichment analysis revealed that they were associated with immune cell infiltration. Besides, the effects of PLAU on the migration and invasion of pancreatic cancer cells were also verified by scratch and transwell experiments. Consequently, CTSK and PLAU have potential as prognostic biomarkers for pancreatic cancer.

Strain induced electrochemical behaviors of ionic liquid electrolytes in an electrochemical double layer capacitor: Insights from molecular dynamics simulations.

Electrochemical Double Layer Capacitors (EDLCs) with ionic liquid electrolytes outperform conventional ones using aqueous and organic electrolytes in energy density and safety. However, understanding the electrochemical behaviors of ionic liquid electrolytes under compressive/tensile strain is essential for the design of flexible EDLCs as well as normal EDLCs, which are subject to external forces during assembly. Despite many experimental studies, the compression/stretching effects on the performance of ionic liquid EDLCs remain inconclusive and controversial. In addition, there is hardly any evidence of prior theoretical work done in this area, which makes the literature on this topic scarce. Herein, for the first time, we developed an atomistic model to study the processes underlying the electrochemical behaviors of ionic liquids in an EDLC under strain. Constant potential non-equilibrium molecular dynamics simulations are conducted for EMIM BF4 placed between two graphene walls as electrodes. Compared to zero strain, low compression of the EDLC resulted in compromised performance as the electrode charge density dropped by 29%, and the performance reduction deteriorated significantly with a further increase in compression. In contrast, stretching is found to enhance the performance by increasing the charge storage in the electrodes by 7%. The performance changes with compression and stretching are due to changes in the double-layer structure. In addition, an increase in the value of the applied potential during the application of strain leads to capacity retention with compression revealed by the newly performed simulations.

Correction: Ding et al. MBD3 as a Potential Biomarker for Colon Cancer: Implications for Epithelial-Mesenchymal Transition (EMT) Pathways. Cancers 2023, 15, 3185.

In the published paper [...].

LncRNA UCA1 promotes pancreatic cancer cell migration by regulating mitochondrial dynamics via the MAPK pathway.

PURPOSE: Long non-coding RNA urothelial cancer associated 1 (UCA1) serves as an oncogene in various cancers. However, the mechanism underlying the role of UCA1 in pancreatic cancer remains unclear. This study aimed to explore the role of UCA1 in pancreatic cancer. METHODS: The expression and prognosis of UCA1 were analyzed using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The results were validated by immunohistochemistry (IHC) and qRT-PCR. The biofunctions of UCA1 were analyzed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). The migration abilities and mitochondrial dynamics of PC cells were examined using the Transwell assay, mitochondrial membrane potential (MMP), and fluorescence. The mitochondrial-related protein and MAPK/ERK pathway markers were evaluated using western blotting. RESULTS: UCA1 expression was significantly higher in pancreatic cancer tissues than in normal tissues. High UCA1 expression indicated poor clinical outcomes and was associated with clinical features in patients with pancreatic cancer. Additionally, high UCA1 expression is a potential independent marker for poor prognosis. Subsequently, we demonstrated that UCA1 enhanced the migration capability, increased MMP, enhanced mitochondrial fusion, and inhibited mitochondrial autophagy in pancreatic cancer cells via the MAPK/ERK pathway. CONCLUSION: UCA1 promotes the migration by regulating the mitochondrial dynamics of pancreatic cancer cells via the MAPK/ERK pathway. Our findings suggest that UCA1 may serve as a potential biomarker in pancreatic cancer prognosis.

Neurosurgical robots in China: State of the art and future prospect.

Neurosurgical robots have developed for decades and can effectively assist surgeons to carry out a variety of surgical operations, such as biopsy, stereo-electroencephalography (SEEG), deep brain stimulation (DBS), and so forth. In recent years, neurosurgical robots in China have developed rapidly. This article will focus on several key skills in neurosurgical robots, such as medical imaging systems, automatic manipulator, lesion localization techniques, multimodal image fusion technology, registration method, and vascular imaging technology; introduce the clinical application of neurosurgical robots in China, and look forward to the potential improvement points in the future based on our experience and research in the field.

The NONRATT023402.2/rno-miR-3065-5p/NGFR axis affects levodopa-induced dyskinesia in a rat model of Parkinson's disease.

Levodopa-induced dyskinesia (LID) is a common motor complication in Parkinson's disease. However, few studies have focused on the pathogenesis of LID at the transcriptional level. NONRATT023402.2, a long non-coding RNA (lncRNA) that may be related to LID was discovered in our previous study and characterized in rat models of LID. In the present study, NONRATT023402.2 was overexpressed by injection of adeno-associated virus (AAV) in striatum of LID rats, and 48 potential target genes, including nerve growth factor receptor (NGFR) were screened using next-generation sequencing and target gene predictions. The NONRATT023402.2/rno-miR-3065-5p/NGFR axis was verified using a dual luciferase reporter gene. Overexpression of NONRATT023402.2 significantly increased the abnormal involuntary movements (AIM) score of LID rats, activated the PI3K/Akt signaling pathway, and up-regulated c-Fos in the striatum. NGFR knockdown by injection of ShNGFR-AAV into the striatum of LID rats resulted in a significant decrease in the PI3K/Akt signaling pathway and c-Fos expression. The AIM score of LID rats was positively correlated with the expressions of NONRATT023402.2 and NGFR. A dual luciferase reporter assay showed that c-Fos, as a transcription factor, bound to the NONRATT023402.2 promoter and activated its expression. Together, the results showed that NONRATT023402.2 regulated NGFR expression via a competing endogenous RNA mechanism, which then activated the PI3K/Akt pathway and promoted c-Fos expression. This suggested that c-Fos acted as a transcription factor to activate NONRATT023402.2 expression, and form a positive feedback regulation loop in LID rats, thus, aggravating LID symptoms. NONRATT023402.2 is therefore a possible novel therapeutic target for LID.

Next-generation magnesium-ion batteries: The quasi-solid-state approach to multivalent metal ion storage.

Mg-ion batteries offer a safe, low-cost, and high-energy density alternative to current Li-ion batteries. However, nonaqueous Mg-ion batteries struggle with poor ionic conductivity, while aqueous batteries face a narrow electrochemical window. Our group previously developed a water-in-salt battery with an operating voltage above 2 V yet still lower than its nonaqueous counterpart because of the dominance of proton over Mg-ion insertion in the cathode. We designed a quasi-solid-state magnesium-ion battery (QSMB) that confines the hydrogen bond network for true multivalent metal ion storage. The QSMB demonstrates an energy density of 264 W·hour kg-1, nearly five times higher than aqueous Mg-ion batteries and a voltage plateau (2.6 to 2.0 V), outperforming other Mg-ion batteries. In addition, it retains 90% of its capacity after 900 cycles at subzero temperatures (-22°C). The QSMB leverages the advantages of aqueous and nonaqueous systems, offering an innovative approach to designing high-performing Mg-ion batteries and other multivalent metal ion batteries.

Identification of Cuproptosis Clusters and Integrative Analyses in Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease; it mainly occurs in the elderly population. Cuproptosis is a newly discovered form of regulated cell death involved in the progression of various diseases. Combining multiple GEO datasets, we analyzed the expression profile and immunity of cuproptosis-related genes (CRGs) in PD. Dysregulated CRGs and differential immune responses were identified between PD and non-PD substantia nigra. Two CRG clusters were defined in PD. Immune analysis suggested that CRG cluster 1 was characterized by a high immune response. The enrichment analysis showed that CRG cluster 1 was significantly enriched in immune activation pathways, such as the Notch pathway and the JAK-STAT pathway. KIAA0319, AGTR1, and SLC18A2 were selected as core genes based on the LASSO analysis. We built a nomogram that can predict the occurrence of PD based on the core genes. Further analysis found that the core genes were significantly correlated with tyrosine hydroxylase activity. This study systematically evaluated the relationship between cuproptosis and PD and established a predictive model for assessing the risk of cuproptosis subtypes and the outcome of PD patients. This study provides a new understanding of PD-related molecular mechanisms and provides new insights into the treatment of PD.

Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy.

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.

Selective activation of TGFß signaling by P. gingivalis-mediated upregulation of GARP aggravates esophageal squamous cell carcinoma.

Aberrant TGFß signaling plays critical roles in the progression of multiple cancers; however, the functional mechanism of this signaling network in the infectious milieu of Esophageal Squamous Cell Carcinoma (ESCC) remains largely unknown. In this study, by using global transcriptomic analysis, we found that Porphyromonas gingivalis infection increased TGFß secretion and promoted the activation of TGFß/Smad signaling in cultured cells and in clinical ESCC samples. Furthermore, we demonstrated for the first time that P. gingivalis enhanced the expression of Glycoprotein A repetitions predominant (GARP), thereby activating TGFß/Smad signaling. Moreover, the increased GARP expression and the subsequent TGFß activation was partially dependent on the fimbriae (FimA) of P. gingivalis. Intriguingly, eliminating P. gingivalis, inhibiting TGFß, or silencing GARP led to a decreased phosphorylation of Smad2/3, the central mediator of TGFß signaling, as well as an attenuated malignant phenotype of ESCC cells, indicating that the activation of TGFß signaling could be an adverse prognostic factor of ESCC. Consistently, our clinical data demonstrated that the phosphorylation of Smad2/3 and the expression of GARP were positively correlated to the poor prognosis of ESCC patients. Lastly, using xenograft models, we found that P. gingivalis infection remarkably activated TGFß signaling and subsequently enhanced the tumor growth and lung metastasis. Collectively, our study indicated that TGFß/Smad signaling mediates the oncogenic function of P. gingivalis in ESCC, which is augmented by the expression of GARP. Therefore, targeting either P. gingivalis or GARP-TGFß signaling could be a potential treatment strategy for patients with ESCC.

MBD3 as a Potential Biomarker for Colon Cancer: Implications for Epithelial-Mesenchymal Transition (EMT) Pathways.

The tumor EMT is a crucial event in tumor pathogenesis and progression. Previous research has established MBD3's significant role in pancreatic cancer EMT. However, MBD3's precise role in colon cancer remains unclear and warrants further investigation. Pan-cancer analysis revealed MBD3's differential expression in various tumors and its significant association with tumor occurrence, growth, and progression. Moreover, analysis of single-cell sequencing and clinical data for colon cancer revealed MBD3 expression's negative correlation with clinical indicators such as survival prognosis. Functional enrichment analysis confirmed the association between MBD3 and EMT in colon cancer. Pathological examinations, western blotting, and qRT-PCR in vitro and in vivo validated MBD3's differential expression in colon cancer. Transwell, CCK-8, clone formation, and in vivo tumorigenesis experiments confirmed MBD3's impact on migration, invasion, and proliferation. Our findings demonstrate MBD3 as a potential prognostic marker and therapeutic target for colon cancer.

SPI1-mediated MIR222HG transcription promotes proneural-to-mesenchymal transition of glioma stem cells and immunosuppressive polarization of macrophages.

Background: Glioma stem cells (GSCs) are a key factor in glioblastoma (GBM) development and treatment resistance. GSCs can be divided into the mesenchymal (MES) and proneural (PN) subtypes, and these two subtypes of GSCs can undergo interconversion under certain conditions. MES GSCs have higher malignancy and radioresistance and are closely associated with an immunosuppressive microenvironment. Long noncoding RNAs (lncRNAs) play a broad role in GBM, while the role of GSCs subtype remains unknown. Methods: We performed RNA sequencing to explore the lncRNA expression profile in MES- and PN-subtype GBM tissues. The biological function of a host gene-MIR222HG-in GBM development was confirmed in vitro and in vivo. Specifically, RNA sequencing, RNA pulldown, mass spectrometry, RIP, ChIP, luciferase reporter assays and Co-IP were performed. Results: MIR222HG, the expression of which can be induced by SPI1, has high levels in MES GBM tissues. Functionally, we demonstrated that MIR222HG promotes the MES transition and radioresistance in GSCs in vivo and in vitro. Mechanistically, MIR222HG can bind to the YWHAE/HDAC5 complex to promote the MES transition of GSCs through H4 deacetylation. Moreover, cotranscribed miR221 and miR222 can be delivered to macrophages via exosomes to target SOCS3, causing immunosuppressive polarization. Finally, PLX-4720 sensitivity is associated with SPI1 expression and acts on MES GSCs to enhance radiosensitivity. Conclusions: This study demonstrates that targeting SPI1 to block transcription of the MIR222HG cluster helps to reduce radioresistance and combat the immunosuppressive microenvironment in GBM. PLX-4720 is a potential GBM drug and radiosensitizer.

Hypoxia-elicited Exosomes Promote the Chemoresistance of Pancreatic Cancer Cells by Transferring LncROR via Hippo Signaling.

Recent studies have found that hypoxia contributes to tumor progression and drug resistance by inducing the secretion of exosomes. However, the mechanism underlying this resistance in pancreatic cancer remains to be explored. In this study, we investigated the effect of hypoxia-induced tumor-derived exosomes (Hexo) on stemness and resistance to gemcitabine in pancreatic cancer cells, as well as the molecular mechanisms involved in this process. Firstly, we discovered that hypoxia promoted stemness and induced resistance to gemcitabine in pancreatic cancer cells. Secondly, we showed that exosomes secreted by pancreatic cancer cells under normoxic or hypoxic conditions can be transfected into tumor cells. Thirdly, it was demonstrated that Hexo promotes proliferation, stemness, and resistance to gemcitabine in pancreatic cancer cells, as well as inhibits the apoptosis and cell cycle arrest induced by gemcitabine. Finally, it was verified that Hexo inactivated the Hippo/Yes-associated protein (Hippo/YAP) pathway in pancreatic cancer cells by transferring exosomal long non-coding RNA regulator of reprogramming (lncROR). In summary, the hypoxic tumor microenvironment could promote stemness and induce resistance to gemcitabine in pancreatic cancer cells. Mechanistically, Hexo enhanced stemness to promote chemoresistance in pancreatic cancer cells by transferring lncROR via Hippo signaling. Thus, exosomal lncROR may serve as a candidate target of chemotherapy for pancreatic cancer.

LncRNA FAM83A-AS1 promotes epithelial-mesenchymal transition of pancreatic cancer cells via Hippo pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been proved to play a vital role in pancreatic cancer (PC). However, the role of lncRNA FAM83A-AS1 in PC remains unclear. In this study, we explored the biological function and underlying mechanism of FAM83A-AS1 in PC cells. METHODS: The FAM83A-AS1 expression was assessed via public databases and validated by qRT-PCR. The biofunction and immune cell infiltration of FAM83A-AS1 were analyzed through GO, KEGG, GESA and ssGSEA. The migration, invasion and proliferation abilities of PC cells were examined by Transwell, wound healing, CCK8 and colony formation. The EMT and Hippo pathway markers were evaluated by western blot. RESULTS: FAM83A-AS1 expression was higher in PC tissues and cells than normal. Additionally, FAM83A-AS1 was associated with poor prognosis of PC and involved in cadherin binding and immune infiltration. Subsequently, we proved FAM83A-AS1 overexpression enhanced the migration, invasion and proliferation abilities of PC cells, whereas FAM83A-AS1 downregulation inhibited those. Moreover, western blot results showed that FAM83A-AS1 knockdown increased the E-cadherin expression and decreased the expression of N-cadherin, ß-catenin, Vimentin, Snail and Slug. On the contrary, FAM83A-AS1 upregulation results in the opposite effects. Besides, FAM83A-AS1 overexpression inhibited the expression of p-YAP, p-MOB1, p-Lats1, SAV1, MST1 and MST2 as well as the results of FAM83A-AS1 knockdown were opposite. CONCLUSION: FAM83A-AS1 promoted EMT of PC cells via Hippo signaling inactivation and may be a potential diagnosis and prognosis target.

Subthalamic nucleus stimulation attenuates motor seizures via modulating the nigral orexin pathway.

Background: Focal motor seizures that originate in the motor region are a considerable challenge because of the high risk of permanent motor deficits after resection. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a potential treatment for motor epilepsy that may enhance the antiepileptic actions of the substantia nigra pars reticulata (SNr). Orexin and its receptors have a relationship with both STN-DBS and epilepsy. We aimed to investigate whether and how STN inputs to the SNr regulate seizures and the role of the orexin pathway in this process. Methods: A penicillin-induced motor epileptic model in adult male C57BL/6 J mice was established to evaluate the efficacy of STN-DBS in modulating seizure activities. Optogenetic and chemogenetic approaches were employed to regulate STN-SNr circuits. Selective orexin receptor type 1 and 2 antagonists were used to inhibit the orexin pathway. Results: First, we found that high-frequency ipsilateral or bilateral STN-DBS was effective in reducing seizure activity in the penicillin-induced motor epilepsy model. Second, inhibition of STN excitatory neurons and STN-SNr projections alleviates seizure activities, whereas their activation amplifies seizure activities. In addition, activation of the STN-SNr circuits also reversed the protective effect of STN-DBS on motor epilepsy. Finally, we observed that STN-DBS reduced the elevated expression of orexin and its receptors in the SNr during seizures and that using a combination of selective orexin receptor antagonists also reduced seizure activity. Conclusion: STN-DBS helps reduce motor seizure activity by inhibiting the STN-SNr circuit. Additionally, orexin receptor antagonists show potential in suppressing motor seizure activity and may be a promising therapeutic option in the future.