Image_4_Porphyromonas gingivalis-induced periodontitis could contribute to cognitive impairment in Sprague–Dawley rats via the P38 MAPK signaling pathway.JPEG

BackgroundPeriodontitis is one of the most common oral diseases and has been shown to be a risk factor for systemic diseases. Our aim was to investigate the relationship between periodontitis and cognitive impairment and to explore the role of the P38 MAPK signaling pathway in this process.MethodsWe established a periodontitis model by ligating the first molars of SD rats with silk thread and injecting Porphyromonas gingivalis (P. gingivalis) or P. gingivalis plus the P38 MAPK inhibitor SB203580 at the same time for ten weeks. We assessed alveolar bone resorption and spatial learning and memory using microcomputed tomography and the Morris water maze test, respectively. We used transcriptome sequencing to explore the genetic differences between the groups. The gingival tissue, peripheral blood and hippocampal tissue were assessed for the cytokines TNF-α, IL-1β, IL-6, IL-8 and C reactive protein (CRP) with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT–PCR). We observed the presence of P. gingivalis in the hippocampus of rats by paraffin-fluorescence in situ hybridization (FISH). We determined the activation of microglia by immunofluorescence. Finally, Western blot analysis was employed to determine the expression of amyloid precursor protein (APP), β-site APP-cleaving enzyme 1 (BACE1) and P38MAPK pathway activation.ResultsWe demonstrated that silk ligature-induced periodontitis plus injection of P. gingivalis into subgingival tissue could lead to memory and cognitive impairment. Transcriptome sequencing results suggested that there were neurodegenerative diseases in the P. gingivalis group, and the MWM test showed that periodontitis reduced the spatial learning and memory ability of mild cognitive impairment (MCI) model rats. We found high levels of inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8) and CRP in the gingiva, peripheral blood and hippocampus, and the expression of APP and BACE1 was upregulated, as was the P38 MAPK pathway activation. Activated microglia and the presence of P. gingivalis were also found in the hippocampus. P38 MAPK inhibitors mitigated all of these changes.ConclusionOur findings strongly suggest that topical application of P. gingivalis increases the inflammatory burden in the peripheral and central nervous systems (CNS) and that neuroinflammation induced by activation of P38 MAPK leads to impaired learning and memory in SD rats. It can also modulate APP processing. Therefore, P38 MAPK may serve as a linking pathway between periodontitis and cognitive impairment.</p

Image_3_Porphyromonas gingivalis-induced periodontitis could contribute to cognitive impairment in Sprague–Dawley rats via the P38 MAPK signaling pathway.JPEG

BackgroundPeriodontitis is one of the most common oral diseases and has been shown to be a risk factor for systemic diseases. Our aim was to investigate the relationship between periodontitis and cognitive impairment and to explore the role of the P38 MAPK signaling pathway in this process.MethodsWe established a periodontitis model by ligating the first molars of SD rats with silk thread and injecting Porphyromonas gingivalis (P. gingivalis) or P. gingivalis plus the P38 MAPK inhibitor SB203580 at the same time for ten weeks. We assessed alveolar bone resorption and spatial learning and memory using microcomputed tomography and the Morris water maze test, respectively. We used transcriptome sequencing to explore the genetic differences between the groups. The gingival tissue, peripheral blood and hippocampal tissue were assessed for the cytokines TNF-α, IL-1β, IL-6, IL-8 and C reactive protein (CRP) with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT–PCR). We observed the presence of P. gingivalis in the hippocampus of rats by paraffin-fluorescence in situ hybridization (FISH). We determined the activation of microglia by immunofluorescence. Finally, Western blot analysis was employed to determine the expression of amyloid precursor protein (APP), β-site APP-cleaving enzyme 1 (BACE1) and P38MAPK pathway activation.ResultsWe demonstrated that silk ligature-induced periodontitis plus injection of P. gingivalis into subgingival tissue could lead to memory and cognitive impairment. Transcriptome sequencing results suggested that there were neurodegenerative diseases in the P. gingivalis group, and the MWM test showed that periodontitis reduced the spatial learning and memory ability of mild cognitive impairment (MCI) model rats. We found high levels of inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8) and CRP in the gingiva, peripheral blood and hippocampus, and the expression of APP and BACE1 was upregulated, as was the P38 MAPK pathway activation. Activated microglia and the presence of P. gingivalis were also found in the hippocampus. P38 MAPK inhibitors mitigated all of these changes.ConclusionOur findings strongly suggest that topical application of P. gingivalis increases the inflammatory burden in the peripheral and central nervous systems (CNS) and that neuroinflammation induced by activation of P38 MAPK leads to impaired learning and memory in SD rats. It can also modulate APP processing. Therefore, P38 MAPK may serve as a linking pathway between periodontitis and cognitive impairment.</p

Image_1_Porphyromonas gingivalis-induced periodontitis could contribute to cognitive impairment in Sprague–Dawley rats via the P38 MAPK signaling pathway.JPEG

BackgroundPeriodontitis is one of the most common oral diseases and has been shown to be a risk factor for systemic diseases. Our aim was to investigate the relationship between periodontitis and cognitive impairment and to explore the role of the P38 MAPK signaling pathway in this process.MethodsWe established a periodontitis model by ligating the first molars of SD rats with silk thread and injecting Porphyromonas gingivalis (P. gingivalis) or P. gingivalis plus the P38 MAPK inhibitor SB203580 at the same time for ten weeks. We assessed alveolar bone resorption and spatial learning and memory using microcomputed tomography and the Morris water maze test, respectively. We used transcriptome sequencing to explore the genetic differences between the groups. The gingival tissue, peripheral blood and hippocampal tissue were assessed for the cytokines TNF-α, IL-1β, IL-6, IL-8 and C reactive protein (CRP) with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT–PCR). We observed the presence of P. gingivalis in the hippocampus of rats by paraffin-fluorescence in situ hybridization (FISH). We determined the activation of microglia by immunofluorescence. Finally, Western blot analysis was employed to determine the expression of amyloid precursor protein (APP), β-site APP-cleaving enzyme 1 (BACE1) and P38MAPK pathway activation.ResultsWe demonstrated that silk ligature-induced periodontitis plus injection of P. gingivalis into subgingival tissue could lead to memory and cognitive impairment. Transcriptome sequencing results suggested that there were neurodegenerative diseases in the P. gingivalis group, and the MWM test showed that periodontitis reduced the spatial learning and memory ability of mild cognitive impairment (MCI) model rats. We found high levels of inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8) and CRP in the gingiva, peripheral blood and hippocampus, and the expression of APP and BACE1 was upregulated, as was the P38 MAPK pathway activation. Activated microglia and the presence of P. gingivalis were also found in the hippocampus. P38 MAPK inhibitors mitigated all of these changes.ConclusionOur findings strongly suggest that topical application of P. gingivalis increases the inflammatory burden in the peripheral and central nervous systems (CNS) and that neuroinflammation induced by activation of P38 MAPK leads to impaired learning and memory in SD rats. It can also modulate APP processing. Therefore, P38 MAPK may serve as a linking pathway between periodontitis and cognitive impairment.</p

Image_5_Porphyromonas gingivalis-induced periodontitis could contribute to cognitive impairment in Sprague–Dawley rats via the P38 MAPK signaling pathway.JPEG

BackgroundPeriodontitis is one of the most common oral diseases and has been shown to be a risk factor for systemic diseases. Our aim was to investigate the relationship between periodontitis and cognitive impairment and to explore the role of the P38 MAPK signaling pathway in this process.MethodsWe established a periodontitis model by ligating the first molars of SD rats with silk thread and injecting Porphyromonas gingivalis (P. gingivalis) or P. gingivalis plus the P38 MAPK inhibitor SB203580 at the same time for ten weeks. We assessed alveolar bone resorption and spatial learning and memory using microcomputed tomography and the Morris water maze test, respectively. We used transcriptome sequencing to explore the genetic differences between the groups. The gingival tissue, peripheral blood and hippocampal tissue were assessed for the cytokines TNF-α, IL-1β, IL-6, IL-8 and C reactive protein (CRP) with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT–PCR). We observed the presence of P. gingivalis in the hippocampus of rats by paraffin-fluorescence in situ hybridization (FISH). We determined the activation of microglia by immunofluorescence. Finally, Western blot analysis was employed to determine the expression of amyloid precursor protein (APP), β-site APP-cleaving enzyme 1 (BACE1) and P38MAPK pathway activation.ResultsWe demonstrated that silk ligature-induced periodontitis plus injection of P. gingivalis into subgingival tissue could lead to memory and cognitive impairment. Transcriptome sequencing results suggested that there were neurodegenerative diseases in the P. gingivalis group, and the MWM test showed that periodontitis reduced the spatial learning and memory ability of mild cognitive impairment (MCI) model rats. We found high levels of inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8) and CRP in the gingiva, peripheral blood and hippocampus, and the expression of APP and BACE1 was upregulated, as was the P38 MAPK pathway activation. Activated microglia and the presence of P. gingivalis were also found in the hippocampus. P38 MAPK inhibitors mitigated all of these changes.ConclusionOur findings strongly suggest that topical application of P. gingivalis increases the inflammatory burden in the peripheral and central nervous systems (CNS) and that neuroinflammation induced by activation of P38 MAPK leads to impaired learning and memory in SD rats. It can also modulate APP processing. Therefore, P38 MAPK may serve as a linking pathway between periodontitis and cognitive impairment.</p

Image_2_Porphyromonas gingivalis-induced periodontitis could contribute to cognitive impairment in Sprague–Dawley rats via the P38 MAPK signaling pathway.JPEG

BackgroundPeriodontitis is one of the most common oral diseases and has been shown to be a risk factor for systemic diseases. Our aim was to investigate the relationship between periodontitis and cognitive impairment and to explore the role of the P38 MAPK signaling pathway in this process.MethodsWe established a periodontitis model by ligating the first molars of SD rats with silk thread and injecting Porphyromonas gingivalis (P. gingivalis) or P. gingivalis plus the P38 MAPK inhibitor SB203580 at the same time for ten weeks. We assessed alveolar bone resorption and spatial learning and memory using microcomputed tomography and the Morris water maze test, respectively. We used transcriptome sequencing to explore the genetic differences between the groups. The gingival tissue, peripheral blood and hippocampal tissue were assessed for the cytokines TNF-α, IL-1β, IL-6, IL-8 and C reactive protein (CRP) with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT–PCR). We observed the presence of P. gingivalis in the hippocampus of rats by paraffin-fluorescence in situ hybridization (FISH). We determined the activation of microglia by immunofluorescence. Finally, Western blot analysis was employed to determine the expression of amyloid precursor protein (APP), β-site APP-cleaving enzyme 1 (BACE1) and P38MAPK pathway activation.ResultsWe demonstrated that silk ligature-induced periodontitis plus injection of P. gingivalis into subgingival tissue could lead to memory and cognitive impairment. Transcriptome sequencing results suggested that there were neurodegenerative diseases in the P. gingivalis group, and the MWM test showed that periodontitis reduced the spatial learning and memory ability of mild cognitive impairment (MCI) model rats. We found high levels of inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8) and CRP in the gingiva, peripheral blood and hippocampus, and the expression of APP and BACE1 was upregulated, as was the P38 MAPK pathway activation. Activated microglia and the presence of P. gingivalis were also found in the hippocampus. P38 MAPK inhibitors mitigated all of these changes.ConclusionOur findings strongly suggest that topical application of P. gingivalis increases the inflammatory burden in the peripheral and central nervous systems (CNS) and that neuroinflammation induced by activation of P38 MAPK leads to impaired learning and memory in SD rats. It can also modulate APP processing. Therefore, P38 MAPK may serve as a linking pathway between periodontitis and cognitive impairment.</p

An All-in-One, Bioderived, Air-Permeable, and Sweat-Stable MXene Epidermal Electrode for Muscle Theranostics

Muscle fatigue is a common symptom experienced by many people and associated with less maximal force production of fatigued muscle. It is highly desirable to simultaneously and imperceivably diagnose muscle fatigue and restore muscle function using one skin electrode, yet no such electrode has been developed so far. Herein, we report an all-in-one, bioderived, air-permeable, and sweat-stable MXene electrode that can concurrently and comfortably record electromyographic (EMG) signals and achieve electrostimulation and electrothermal therapy for muscle theranostics. Leveraging the structural arrangement of perennial herbs and ion cross-linking of MXene in sweat, MXene-based electrodes (MBE) exhibit high breathability, are ultralightweight (∼0.25 mg/cm3), and have low and stable electrode–skin interfacial impedance at a variety of environments, facilitating the long-term reliable monitoring of electrophysiology. Taken together with electrostimulation and electrothermal therapy at the skin surface, MBE can diagnose muscle fatigue and restore muscle function by stimulating blood circulation. In addition, it can also be used for muscle rehabilitation training and prosthesis control via human–computer interaction. Our all-in-one, bioderived, air-permeable, and sweat-stable MXene electrode has a great potential for daily wearable healthcare of muscle fatigue

Dynamic Ag–N Bond Enhanced Stretchable Conductor for Transparent and Self-Healing Electronic Skin

Stretchable conductors have been achieved by stacking conductive nanomaterials onto the surfaces of elastomeric substrates. However, many of them show a dramatic decrease in conductivity under strain without an efficient way for the conductive layer to release strain. Here, we report a transparent, stretchable, and self-healing conductor with excellent mechanoelectrical stability by introducing dynamic bonding between conductive nanomaterials and an elastomeric substrate. We prepare the conductor by semiembedding Ag nanowires (AgNWs) into a self-healing polydimethylsiloxane (PDMS)-based elastomer, which is modified with bipyridine (Bpy) ligand and further cross-linked by adding Zn2+ as coordinator (Zn–Bpy–PDMS). The dynamic Ag–N bonds not only improve the wettability of the substrate and facilitate the spreading of AgNWs but also reversibly break and reform to accommodate the deformation of AgNWs. As a result, the resistance increase of Zn–Bpy–PDMS/AgNWs is much smaller than that without the dynamic bonding (PDMS/AgNWs). Besides, this conductor exhibits excellent conductivity (76.2 Ω/sq) and transparency (86.6% @ 550 nm), as well as extraordinary self-healing property with a low resistance increase (ΔR/R0 ∼ 1.4) after healing at room temperature for 1 day. This work provides insights into the future design of integrated electronic skin with transparency, stretchability, conductivity, and self-healing capability for applications in wearable optoelectronic devices

Dynamic Ag–N Bond Enhanced Stretchable Conductor for Transparent and Self-Healing Electronic Skin

Stretchable conductors have been achieved by stacking conductive nanomaterials onto the surfaces of elastomeric substrates. However, many of them show a dramatic decrease in conductivity under strain without an efficient way for the conductive layer to release strain. Here, we report a transparent, stretchable, and self-healing conductor with excellent mechanoelectrical stability by introducing dynamic bonding between conductive nanomaterials and an elastomeric substrate. We prepare the conductor by semiembedding Ag nanowires (AgNWs) into a self-healing polydimethylsiloxane (PDMS)-based elastomer, which is modified with bipyridine (Bpy) ligand and further cross-linked by adding Zn2+ as coordinator (Zn–Bpy–PDMS). The dynamic Ag–N bonds not only improve the wettability of the substrate and facilitate the spreading of AgNWs but also reversibly break and reform to accommodate the deformation of AgNWs. As a result, the resistance increase of Zn–Bpy–PDMS/AgNWs is much smaller than that without the dynamic bonding (PDMS/AgNWs). Besides, this conductor exhibits excellent conductivity (76.2 Ω/sq) and transparency (86.6% @ 550 nm), as well as extraordinary self-healing property with a low resistance increase (ΔR/R0 ∼ 1.4) after healing at room temperature for 1 day. This work provides insights into the future design of integrated electronic skin with transparency, stretchability, conductivity, and self-healing capability for applications in wearable optoelectronic devices

Dynamic Ag–N Bond Enhanced Stretchable Conductor for Transparent and Self-Healing Electronic Skin

Stretchable conductors have been achieved by stacking conductive nanomaterials onto the surfaces of elastomeric substrates. However, many of them show a dramatic decrease in conductivity under strain without an efficient way for the conductive layer to release strain. Here, we report a transparent, stretchable, and self-healing conductor with excellent mechanoelectrical stability by introducing dynamic bonding between conductive nanomaterials and an elastomeric substrate. We prepare the conductor by semiembedding Ag nanowires (AgNWs) into a self-healing polydimethylsiloxane (PDMS)-based elastomer, which is modified with bipyridine (Bpy) ligand and further cross-linked by adding Zn2+ as coordinator (Zn–Bpy–PDMS). The dynamic Ag–N bonds not only improve the wettability of the substrate and facilitate the spreading of AgNWs but also reversibly break and reform to accommodate the deformation of AgNWs. As a result, the resistance increase of Zn–Bpy–PDMS/AgNWs is much smaller than that without the dynamic bonding (PDMS/AgNWs). Besides, this conductor exhibits excellent conductivity (76.2 Ω/sq) and transparency (86.6% @ 550 nm), as well as extraordinary self-healing property with a low resistance increase (ΔR/R0 ∼ 1.4) after healing at room temperature for 1 day. This work provides insights into the future design of integrated electronic skin with transparency, stretchability, conductivity, and self-healing capability for applications in wearable optoelectronic devices

Image_1_Molecular Expression Profile of Changes in Rat Acute Spinal Cord Injury.tif

Background: Spinal cord injury (SCI) is a highly lethal and debilitating disease with a variety of etiologies. To date, there is no effective therapeutic modality for a complete cure. The pathological mechanisms of spinal cord injury at the molecular gene and protein expression levels remain unclear.Methods: This study used single-cell transcriptomic analysis and protein microarray analysis to analyzes changes in the gene expression profiles of cells and secretion of inflammatory factors respectively, around the lesion site in a rat SCI model.Results: Single-cell transcriptomic analysis found that three types of glial cells (microglia, astrocyte, and oligodendrocyte) becomes activated after acute injury, with GO exhibiting a variety of inflammatory-related terms after injury, such as metabolic processes, immune regulation, and antigen presentation. Protein microarray results showed that the levels of four inflammatory cytokines favoring SCI repair decreased while the levels of nine inflammatory cytokines hindering SCI repair increased after injury.Conclusion: These findings thus reveal the changes in cellular state from homeostatic to reactive cell type after SCI, which contribute to understand the pathology process of SCI, and the potential relationship between glial cells and inflammatory factors after SCI, and provides new theoretical foundation for further elucidating the molecular mechanisms of secondary SCI.</p