Image_1_Exploring the pathogenesis linking traumatic brain injury and epilepsy via bioinformatic analyses.JPEG

Traumatic brain injury (TBI) is a serious disease that could increase the risk of epilepsy. The purpose of this article is to explore the common molecular mechanism in TBI and epilepsy with the aim of providing a theoretical basis for the prevention and treatment of post-traumatic epilepsy (PTE). Two datasets of TBI and epilepsy in the Gene Expression Omnibus (GEO) database were downloaded. Functional enrichment analysis, protein–protein interaction (PPI) network construction, and hub gene identification were performed based on the cross-talk genes of aforementioned two diseases. Another dataset was used to validate these hub genes. Moreover, the abundance of infiltrating immune cells was evaluated through Immune Cell Abundance Identifier (ImmuCellAI). The common microRNAs (miRNAs) between TBI and epilepsy were acquired via the Human microRNA Disease Database (HMDD). The overlapped genes in cross-talk genes and target genes predicted through the TargetScan were obtained to construct the common miRNAs–mRNAs network. A total of 106 cross-talk genes were screened out, including 37 upregulated and 69 downregulated genes. Through the enrichment analyses, we showed that the terms about cytokine and immunity were enriched many times, particularly interferon gamma signaling pathway. Four critical hub genes were screened out for co-expression analysis. The miRNA–mRNA network revealed that three miRNAs may affect the shared interferon-induced genes, which might have essential roles in PTE. Our study showed the potential role of interferon gamma signaling pathway in pathogenesis of PTE, which may provide a promising target for future therapeutic interventions.</p

Table_3_Exploring the pathogenesis linking traumatic brain injury and epilepsy via bioinformatic analyses.DOCX

Traumatic brain injury (TBI) is a serious disease that could increase the risk of epilepsy. The purpose of this article is to explore the common molecular mechanism in TBI and epilepsy with the aim of providing a theoretical basis for the prevention and treatment of post-traumatic epilepsy (PTE). Two datasets of TBI and epilepsy in the Gene Expression Omnibus (GEO) database were downloaded. Functional enrichment analysis, protein–protein interaction (PPI) network construction, and hub gene identification were performed based on the cross-talk genes of aforementioned two diseases. Another dataset was used to validate these hub genes. Moreover, the abundance of infiltrating immune cells was evaluated through Immune Cell Abundance Identifier (ImmuCellAI). The common microRNAs (miRNAs) between TBI and epilepsy were acquired via the Human microRNA Disease Database (HMDD). The overlapped genes in cross-talk genes and target genes predicted through the TargetScan were obtained to construct the common miRNAs–mRNAs network. A total of 106 cross-talk genes were screened out, including 37 upregulated and 69 downregulated genes. Through the enrichment analyses, we showed that the terms about cytokine and immunity were enriched many times, particularly interferon gamma signaling pathway. Four critical hub genes were screened out for co-expression analysis. The miRNA–mRNA network revealed that three miRNAs may affect the shared interferon-induced genes, which might have essential roles in PTE. Our study showed the potential role of interferon gamma signaling pathway in pathogenesis of PTE, which may provide a promising target for future therapeutic interventions.</p

Dual-Targeting into the Mitochondria of Cancer Cells for Ratiometric Investigation of the Dynamic Fluctuation of Sulfur Dioxide and Formaldehyde with Two-Photon Integrated Semiconducting Polymer Dots

Mitochondrial sulfur dioxide (SO2) and formaldehyde (FA) in cancer cells serve as important signal molecules in mediating multiple physiological and pathological activities. Accurate monitoring of the dynamic fluctuation of SO2 and FA in the mitochondria of cancer cells is important for insight into their relationships and functions in cancer, understanding cancer mechanism, and the role of mitochondrial homeostasis in cancer invasion and metastasis. Herein, a novel integrated two-photon semiconducting polymer dot (BF@Pdots) with dual-targeting (cancer cells and mitochondrial) and dual-emission in green and red regions, which is rationally designed through a four-step engineering strategy by using two newly synthesized functionalized polymers PFNA and FD-PSMA as precursors, has been developed for accurate tracking of the dynamic variation of SO2 and FA in the mitochondria of cancer cells. The sensing mechanism is on the basis of the fluorescence resonance energy transfer (FRET) process in BF@Pdots tuned by the reversible Michael addition reaction between the sensing-groups and SO2 (or FA). The integrated BF@Pdots nanoprobes display excellent performances in the accurate detection of the dynamic fluctuation of SO2 and FA such as precise positioning in the mitochondria of cancer cells, self-calibrating ratiometric, two-photon emission with long wavelength excitation, and fast reversible response. The BF@Pdots nanoprobes are also applied to the ratiometric detection of the dynamic fluctuation of exogenous and endogenous SO2 and FA in the mitochondria of cancer cells for the first time with satisfactory results. Taken together, this work will provide an attractive way to develop versatile integrated Pdots-based fluorescent probes through flexible molecular engineering for applications in accurate imaging of biomolecules in living systems

Data_Sheet_1_Operation of the Atypical Canonical Bone Morphogenetic Protein Signaling Pathway During Early Human Odontogenesis.PDF

Bone morphogenetic protein (BMP) signaling plays essential roles in the regulation of early tooth development. It is well acknowledged that extracellular BMP ligands bind to the type I and type II transmembrane serine/threonine kinase receptor complexes to trigger the BMP signaling pathway. Then, the receptor-activated Smad1/5/8 in cytoplasm binds to Smad4, the central mediator of the canonical BMP signaling pathway, to form transfer complexes for entering the nucleus and regulating target gene expression. However, a recent study revealed the functional operation of a novel BMP-mediated signaling pathway named the atypical BMP canonical signaling pathway in mouse developing tooth, which is Smad1/5/8 dependent but Smad4 independent. In this study, we investigated whether this atypical BMP canonical signaling is conserved in human odontogenesis. We showed that pSMAD1/5/8 is required for the expression of Msh homeobox 1 (MSX1), a well-defined BMP signaling target gene, in human dental mesenchyme, but the typical BMP canonical signaling is in fact not operating in the early human developing tooth, as evidenced by the absence of pSMAD1/5/8-SMAD4 complexes in the dental mesenchyme and translocation of pSMAD1/5/8, and the expression of MSX1 induced by BMP4 is mothers against decapentaplegic homolog 4 (SMAD4)-independent in human dental mesenchymal cells. Moreover, integrative analysis of RNA-Seq data sets comparing the transcriptome profiles of human dental mesenchymal cells with and without SMAD4 knockdown by siRNA displays unchanged expression profiles of pSMAD1/5/8 downstream target genes, further affirming the functional operation of the atypical canonical BMP signaling pathway in a SMAD1/5/8-dependent but SMAD4-independent manner in the dental mesenchyme during early odontogenesis in humans.</p

Table_1_Exploring the pathogenesis linking traumatic brain injury and epilepsy via bioinformatic analyses.DOCX

Traumatic brain injury (TBI) is a serious disease that could increase the risk of epilepsy. The purpose of this article is to explore the common molecular mechanism in TBI and epilepsy with the aim of providing a theoretical basis for the prevention and treatment of post-traumatic epilepsy (PTE). Two datasets of TBI and epilepsy in the Gene Expression Omnibus (GEO) database were downloaded. Functional enrichment analysis, protein–protein interaction (PPI) network construction, and hub gene identification were performed based on the cross-talk genes of aforementioned two diseases. Another dataset was used to validate these hub genes. Moreover, the abundance of infiltrating immune cells was evaluated through Immune Cell Abundance Identifier (ImmuCellAI). The common microRNAs (miRNAs) between TBI and epilepsy were acquired via the Human microRNA Disease Database (HMDD). The overlapped genes in cross-talk genes and target genes predicted through the TargetScan were obtained to construct the common miRNAs–mRNAs network. A total of 106 cross-talk genes were screened out, including 37 upregulated and 69 downregulated genes. Through the enrichment analyses, we showed that the terms about cytokine and immunity were enriched many times, particularly interferon gamma signaling pathway. Four critical hub genes were screened out for co-expression analysis. The miRNA–mRNA network revealed that three miRNAs may affect the shared interferon-induced genes, which might have essential roles in PTE. Our study showed the potential role of interferon gamma signaling pathway in pathogenesis of PTE, which may provide a promising target for future therapeutic interventions.</p

Image_2_Exploring the pathogenesis linking traumatic brain injury and epilepsy via bioinformatic analyses.JPEG

Traumatic brain injury (TBI) is a serious disease that could increase the risk of epilepsy. The purpose of this article is to explore the common molecular mechanism in TBI and epilepsy with the aim of providing a theoretical basis for the prevention and treatment of post-traumatic epilepsy (PTE). Two datasets of TBI and epilepsy in the Gene Expression Omnibus (GEO) database were downloaded. Functional enrichment analysis, protein–protein interaction (PPI) network construction, and hub gene identification were performed based on the cross-talk genes of aforementioned two diseases. Another dataset was used to validate these hub genes. Moreover, the abundance of infiltrating immune cells was evaluated through Immune Cell Abundance Identifier (ImmuCellAI). The common microRNAs (miRNAs) between TBI and epilepsy were acquired via the Human microRNA Disease Database (HMDD). The overlapped genes in cross-talk genes and target genes predicted through the TargetScan were obtained to construct the common miRNAs–mRNAs network. A total of 106 cross-talk genes were screened out, including 37 upregulated and 69 downregulated genes. Through the enrichment analyses, we showed that the terms about cytokine and immunity were enriched many times, particularly interferon gamma signaling pathway. Four critical hub genes were screened out for co-expression analysis. The miRNA–mRNA network revealed that three miRNAs may affect the shared interferon-induced genes, which might have essential roles in PTE. Our study showed the potential role of interferon gamma signaling pathway in pathogenesis of PTE, which may provide a promising target for future therapeutic interventions.</p

Table_2_Exploring the pathogenesis linking traumatic brain injury and epilepsy via bioinformatic analyses.DOCX

Traumatic brain injury (TBI) is a serious disease that could increase the risk of epilepsy. The purpose of this article is to explore the common molecular mechanism in TBI and epilepsy with the aim of providing a theoretical basis for the prevention and treatment of post-traumatic epilepsy (PTE). Two datasets of TBI and epilepsy in the Gene Expression Omnibus (GEO) database were downloaded. Functional enrichment analysis, protein–protein interaction (PPI) network construction, and hub gene identification were performed based on the cross-talk genes of aforementioned two diseases. Another dataset was used to validate these hub genes. Moreover, the abundance of infiltrating immune cells was evaluated through Immune Cell Abundance Identifier (ImmuCellAI). The common microRNAs (miRNAs) between TBI and epilepsy were acquired via the Human microRNA Disease Database (HMDD). The overlapped genes in cross-talk genes and target genes predicted through the TargetScan were obtained to construct the common miRNAs–mRNAs network. A total of 106 cross-talk genes were screened out, including 37 upregulated and 69 downregulated genes. Through the enrichment analyses, we showed that the terms about cytokine and immunity were enriched many times, particularly interferon gamma signaling pathway. Four critical hub genes were screened out for co-expression analysis. The miRNA–mRNA network revealed that three miRNAs may affect the shared interferon-induced genes, which might have essential roles in PTE. Our study showed the potential role of interferon gamma signaling pathway in pathogenesis of PTE, which may provide a promising target for future therapeutic interventions.</p

Table_1_Operation of the Atypical Canonical Bone Morphogenetic Protein Signaling Pathway During Early Human Odontogenesis.XLSX

Bone morphogenetic protein (BMP) signaling plays essential roles in the regulation of early tooth development. It is well acknowledged that extracellular BMP ligands bind to the type I and type II transmembrane serine/threonine kinase receptor complexes to trigger the BMP signaling pathway. Then, the receptor-activated Smad1/5/8 in cytoplasm binds to Smad4, the central mediator of the canonical BMP signaling pathway, to form transfer complexes for entering the nucleus and regulating target gene expression. However, a recent study revealed the functional operation of a novel BMP-mediated signaling pathway named the atypical BMP canonical signaling pathway in mouse developing tooth, which is Smad1/5/8 dependent but Smad4 independent. In this study, we investigated whether this atypical BMP canonical signaling is conserved in human odontogenesis. We showed that pSMAD1/5/8 is required for the expression of Msh homeobox 1 (MSX1), a well-defined BMP signaling target gene, in human dental mesenchyme, but the typical BMP canonical signaling is in fact not operating in the early human developing tooth, as evidenced by the absence of pSMAD1/5/8-SMAD4 complexes in the dental mesenchyme and translocation of pSMAD1/5/8, and the expression of MSX1 induced by BMP4 is mothers against decapentaplegic homolog 4 (SMAD4)-independent in human dental mesenchymal cells. Moreover, integrative analysis of RNA-Seq data sets comparing the transcriptome profiles of human dental mesenchymal cells with and without SMAD4 knockdown by siRNA displays unchanged expression profiles of pSMAD1/5/8 downstream target genes, further affirming the functional operation of the atypical canonical BMP signaling pathway in a SMAD1/5/8-dependent but SMAD4-independent manner in the dental mesenchyme during early odontogenesis in humans.</p

Dual-Emission Carbonized Polymer Dots for Ratiometric pH Sensing, pH-Dependent Generation of Singlet Oxygen, and Imaging-Guided Dynamics Monitoring of Photodynamic Therapy

The pH environment in cancer cells has been demonstrated to display vital influences on the therapeutic effect of photodynamic therapy (PDT). It is very interesting to develop pH-responsive probes for simultaneous pH sensing and dynamics monitoring of the effects of PDT, and therefore assessing the correlation between them. In this study, a multifunctional fluorescence probe, dual-emission carbonized polymer dot (CPD) in blue and red regions, which uses ethylene imine polymer (PEI) and 4,4′,4″,4‴-(porphine-5, 10, 15, 20-tetrayl) tetrakis (benzoic acid) (TCPP) as precursors through a one-step hydrothermal amide reaction, has been designed for ratiometric pH sensing, generating pH-dependent 1O2 for PDT of cancer cells, and investigating the dynamics effects of PDT through pH-guided imaging. The prepared CPDs were successfully used for ratiometric pH response, pH-dependent generation of 1O2, and dynamics monitoring PDT in HeLa cells. This study may provide an alternative strategy to prepare CPD-based theranostic integrated nanoprobes for PDT through the rational design of precursors