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Viral encephalitis continues to be a significant public health concern. In our previous study, we discovered a lower expression of antiviral factors, such as IFN-ß, STING and IFI16, in the brain tissues of patients with Rasmussen's encephalitis (RE), a rare chronic neurological disorder often occurred in children, characterized by unihemispheric brain atrophy. Furthermore, a higher cumulative viral score of human herpes viruses (HHVs) was also found to have a significant positive correlation with the unihemispheric atrophy in RE. Type I IFNs (IFN-I) signaling is essential for innate anti-infection response by binding to IFN-α/ß receptor (IFNAR). In this study, we infected WT mice and IFNAR-deficient A6 mice with herpes simplex virus 1 (HSV-1) via periocular injection to investigate the relationship between IFN-I signaling and HHVs-induced brain lesions. While all mice exhibited typical viral encephalitis lesions in their brains, HSV-induced epilepsy was only observed in A6 mice. The gene expression matrix, functional enrichment analysis and protein-protein interaction network revealed four gene models that were positively related with HSV-induced epilepsy. Additionally, ten key genes with the highest scores were identified. Taken together, these findings indicate that intact IFN-I signaling can effectively limit HHVs induced neural symptoms and brain lesions, thereby confirming the positive correlation between IFN-I signaling repression and brain atrophy in RE and other HHVs encephalitis.
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Epilepsia , Herpes Simple , Herpesvirus Humano 1 , Interferón Tipo I , Transducción de Señal , Animales , Femenino , Ratones , Encéfalo/patología , Encéfalo/virología , Modelos Animales de Enfermedad , Encefalitis por Herpes Simple/virología , Encefalitis por Herpes Simple/inmunología , Encefalitis por Herpes Simple/patología , Epilepsia/virología , Epilepsia/patología , Herpes Simple/virología , Herpes Simple/patología , Herpes Simple/inmunología , Herpesvirus Humano 1/patogenicidad , Herpesvirus Humano 1/inmunología , Interferón Tipo I/metabolismo , Interferón Tipo I/inmunología , Ratones Endogámicos C57BL , Ratones Noqueados , Mapas de Interacción de Proteínas , Receptor de Interferón alfa y beta/genética , Receptor de Interferón alfa y beta/deficienciaRESUMEN
Itch is a complex and unpleasant sensory experience. Recent studies have begun to investigate the neural mechanisms underlying the modulation of sensory and emotional components of itch in the brain. However, the key brain regions and neural mechanism involved in modulating the attentional processing of itch remain elusive. Here, we showed that the prelimbic cortex (PrL) is associated with itch processing and that the manipulation of itch-responsive neurons in the PrL significantly disrupted itch-induced scratching. Interestingly, we found that increasing attentional bias toward a distracting stimulus could disturb itch processing. We also demonstrated the existence of a population of attention-related neurons in the PrL that drive attentional bias to regulate itch processing. Importantly, itch-responsive neurons and attention-related neurons significantly overlapped in the PrL and were mutually interchangeable in the regulation of itch processing at the cellular activity level. Our results revealed that the PrL regulates itch processing by controlling attentional bias.
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In the past several years, rechargeable zinc batteries, featuring the merits of low cost, environmental friendliness, easy manufacturing, and enhanced safety, have, attracted much attention. Zinc (Zn) anodes for zinc metal batteries play an important role. In this review, the fundamental understanding of these batteries and modification strategies to deal with the problematic issues for Zn anodes, including dendrite growth, corrosion, and the hydrogen evolution phenomenon will be summarized. The practical application of Zn anodes can still lead to Zn dendrites, various side reactions, and serious safety risks. Therefore, metal-free anodes for "rocking chair" zinc ion batteries to replace Zn anodes are systemically reviewed. The performance and the zinc storage mechanism of metal-free anodes will be discussed. Subsequently, a "rocking chair" zinc ion battery prototype selected as a recent example is assessed to explore the merits and demerits of Zn anodes and metal-free anodes. To conclude, a perspective on the future of zinc metal batteries and "rocking chair" zinc ion batteries is presented. It is hoped that this review may provide for further improvement of commercial rechargeable zinc batteries.
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OBJECTIVE: To explore the clinical effect of warming-needle moxibustion with different lengths of moxa stick for asthenospermia with kidney deficiency and liver depression. METHODS: A total of 240 patients with asthenospermia of kidney deficiency and liver depression were randomly divided into a 4-cm group (moxibustion with 4-cm moxa stick, 60 cases, 3 cases dropped off), a 3-cm group (moxibustion with 3-cm moxa stick, 60 cases, 4 cases dropped off), a 2-cm group (moxibustion with 2-cm moxa stick, 60 cases, 2 cases dropped off) and an acupuncture group (60 cases, 3 cases dropped off). All patients were treated with warming-needle moxibustion with different lengths of moxa stick or conventicnal acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Zhongji (CV 3), Guilai (ST 29), Yaoyangguan (GV 3), Guanyuanshu (BL 26), etc., once a day, five times a week; 4-week treatment was taken as one course, a total of two courses of treatment were given. The semen routine indexes, seminal plasma biochemical indexes, sex hormone levels and TCM syndrome score were compared before and after treatment among the 4 groups. RESULTS: After treatment, the sperm density, sperm viability, ratio of grade A sperm, ratio of grade A and B sperm, seminal plasma fructose and neutral α-glucosidase were higher than those before treatment (P<0.05, P<0.01), and the sperm deformity rates were lower than those before treatment in the 4-cm group and the 3-cm group (P<0.01, P<0.05). The ratio of grade A sperm, ratio of grade A and B sperm, seminal plasma fructose and neutral α-glucosidase in the 4-cm group were higher than the other three groups (P<0.05, P<0.01), and the sperm deformity rate was lower than the other three groups (P<0.05). After treatment, except for dizziness and tinnitus score, each-domain score and total scores of TCM syndrome scale in the 4-cm group and the 3-cm group were lower than those before treatment (P<0.01, P<0.05). The each-domain score of depression, weak waist and knees, low sexual function and total score in the 4-cm group were lower than those in the other three groups (P<0.05, P<0.01). The total effective rate was 87.7% (50/57) in the 4-cm group, which was higher than 78.6% (44/56) in the 3-cm group, 77.6% (45/58) in the 2-cm group and 70.2% (40/57) in the acupuncture group (P<0.05, P<0.01). CONCLUSION: The warming-needle moxibustion with 4-cm moxa stick could effectively improve quality and motility of sperm and clinical symptoms in patients with asthenospermia of kidney deficiency and liver depression, which is superior to moxibustion with 3-cm, 2-cm moxa sticks and conventional acupuncture.
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Terapia por Acupuntura , Moxibustión , Puntos de Acupuntura , Depresión , Fructosa , Humanos , Riñón , Hígado , Masculino , Semen , Resultado del Tratamiento , alfa-GlucosidasasRESUMEN
Itch is a cutaneous sensation that is critical in driving scratching behavior. The long-standing question of whether there are specific neurons for itch modulation inside the brain remains unanswered. Here, we report a subpopulation of itch-specific neurons in the ventrolateral orbital cortex (VLO) that is distinct from the pain-related neurons. Using a Tet-Off cellular labeling system, we showed that local inhibition or activation of these itch-specific neurons in the VLO significantly suppressed or enhanced itch-induced scratching, respectively, whereas the intervention did not significantly affect pain. Conversely, suppression or activation of pain-specific neurons in the VLO significantly affected pain but not itch. Moreover, fiber photometry and immunofluorescence verified that these itch- and pain-specific neurons are distinct in their functional activity and histological location. In addition, the downstream targets of itch- and pain-specific neurons were different. Together, the present study uncovers an important subpopulation of neurons in the VLO that specifically modulates itch processing.
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BACKGROUND: The etiology of Rasmussen's encephalitis (RE), a rare chronic neurological disorder characterized by CD8+ T cell infiltration and unihemispheric brain atrophy, is still unknown. Various human herpes viruses (HHVs) have been detected in RE brain, but their contribution to RE pathogenesis is unclear. METHODS: HHVs infection and relevant immune response were compared among brain tissues from RE, temporal lobe epilepsy (TLE) and traumatic brain injury (TBI) patients. Viral antigen or genome, CD8+ T cells, microglia and innate immunity molecules were analyzed by immunohistochemical staining, DNA dot blot assay or immunofluorescence double staining. Cytokines were measured by multiplex flow cytometry. Cell apoptosis was visualized by TUNEL staining. Viral infection, immune response and the severity of unihemispheric atrophy were subjected to correlation analysis. RESULTS: Antigens of various HHVs were prevalent in RE and TLE brains, and the cumulative viral score of HHVs positively correlated with the unihemispheric atrophy in RE patients. CD8+ T cells infiltration were observed in both RE and TLE brains and showed co-localization with HHV antigens, but their activation, as revealed by Granzyme B (GZMB) release and apoptosis, was found only in RE. In comparison to TLE, RE brain tissues contained higher level of inflammatory cytokines, but the interferon-ß level, which was negatively correlated with cumulative viral score, was relatively lower. In line with this, the DNA sensor STING and IFI16, rather than other innate immunity signaling molecules, were insufficiently activated in RE. CONCLUSIONS: Compared with TBI, both RE and TLE had prevalently HHV infection and immune response in brain tissues. However, in comparison to TLE, RE showed insufficient activation of antiviral innate immunity but overactivation of cytotoxic T cells. Our results show the relatively lower level of antiviral innate immunity and overactivation of cytotoxic T cells in RE cases upon HHV infection, the overactivated T cells might be a compensate to the innate immunity but the causative evidence is lack in our study and need more investigation in the future.
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Encefalitis , Epilepsia del Lóbulo Temporal , Virus , Encéfalo/metabolismo , Encefalitis/patología , Epilepsia del Lóbulo Temporal/patología , Humanos , Interferón beta , Virus/metabolismoRESUMEN
The Pd-catalyzed carbene coupling reaction of N-tosylhydrazones and benzyl bromides has been developed into a polymerization process for the first time, providing an efficient method for the synthesis of poly(arylene vinylene)s (PAVs). This method affords PAVs bearing E-vinylene units predominantly. It can also introduce a CF3 group on each vinylene carbon atom in the polymer main chain. The polymerization has a broad scope and the resultant polymers exhibit interesting optical properties and good thermal stabilities.
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OBJECTIVE: Rasmussen's encephalitis (RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses such as human cytomegalovirus (HCMV) has been hypothesized to be a potential trigger for RE. Interferon-induced transmembrane protein-3 (IFITM3) single-nucleotide polymorphism (SNP) rs12252 is associated with the severity of viral infection disease. This study aimed to address the possibility that HCMV infection and IFITM3 rs12252 might be associated with RE disease progression. METHODS: The expression of HCMV and IFITM3 was detected with immunohistochemical staining, in situ hybridization and immunofluorescence double staining. The genotype of IFITM3 rs12252 was detected using the Sanger sequencing method. A genetic association analysis was carried out for this SNP and HCMV antigen expression. The relationship between this SNP and the clinical characteristics of these patients was further analyzed. In in vitro study, HCMV replication in SH-SY5Y cells with overexpressed IFITM3 variant was detected by immunofluorescence and real-time RT-PCR. RESULTS: Elevated expression of HCMV and IFITM3 was observed in the brain tissue of RE patients. Moreover, the IFITM3 polymorphism rs12252-C was found to associate with HCMV high detection and rapid disease progression in RE patients with the IFITM3 rs12252-CC genotype. In vitro study showed the overexpressed IFITM3 variant was associated with HCMV high infection level. CONCLUSION: These results suggest that the IFITM3 rs12252-C is associated with the disease progression of RE patients via facilitating persistent HCMV infection in brain tissue and provides new insight into understanding the pathogenesis of RE.
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Infecciones por Citomegalovirus , Citomegalovirus , Progresión de la Enfermedad , Encefalitis , Proteínas de la Membrana/genética , Proteínas de Unión al ARN/genética , Células Cultivadas , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/genética , Infecciones por Citomegalovirus/metabolismo , Infecciones por Citomegalovirus/virología , Encefalitis/genética , Encefalitis/metabolismo , Encefalitis/virología , Encefalitis Viral/genética , Encefalitis Viral/metabolismo , Encefalitis Viral/virología , Genotipo , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: To determine the effects of Ginkgo biloba extract (EGB) on major periodontal pathogens in subgingival plaque. METHODS: Sixty patients with moderate to severe periodontitis were selected and randomly assigned to 3 groups: EGB group, a positive (periocline) and a negative control groups. Subgingival plaque samples were collected before treatment and 1 week, 2 months and 4 months after treatment. The detection rates of 4 major periodontal pathogens-Treponema denticola (Td), Tannerella forsythus (Tf), Prevotella intermedia (Pi), and Porphyromonas gingivalis (Pg)-were detected by polymerase chain reaction (PCR). Clinical indicators were examined before treatment, 3 and 6 months after treatment. RESULTS: EGB significantly decreased the detection rate of all the 4 pathogens 1 week after treatment, and then gradually increased at 2 and 4 months. EGB's inhibition effect was better than or comparable to periocline, except for Pg in short-term. The difference of plaque index (PLI) and bleeding index (BI) was not statistically significant among the groups, while for probing depth (PD) and attachment loss (AL), the difference was statistically significant between the EGB group and negative control group at 3 and 6 months after treatment. CONCLUSION: EGB significantly inhibited major periodontal pathogens and can be used as an adjuvant for periodontitis treatment.
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Adyuvantes Farmacéuticos/farmacología , Bacterias/efectos de los fármacos , Placa Dental/tratamiento farmacológico , Placa Dental/microbiología , Ginkgo biloba/química , Periodoncio/microbiología , Extractos Vegetales/farmacología , Adyuvantes Farmacéuticos/uso terapéutico , Bacterias/aislamiento & purificación , Estudios de Seguimiento , Humanos , Periodoncio/efectos de los fármacos , Periodoncio/patología , Extractos Vegetales/uso terapéutico , Reacción en Cadena de la Polimerasa , Resultado del TratamientoRESUMEN
AIM: To investigate the regulatory effects and the related mechanisms of streptococcal protein on the immunologic activity of RAW264.7 murine macrophages. METHODS: RAW264.7 cells were incubated with different concentrated streptococcal protein respectively. The proliferation of RAW264.7 cells was determined by MTT assay. The phagocytosis of macrophages was analyzed by neutral red phagocytosis assay. The activities of IL-6 and TNF-alpha in the cultured supernatants were measured by bio-chemical methods. The mRNA expression of TNF-alpha, IL-6 and Toll-like receptors (TLRs) in cells was detected by reverse transcription polymerase chain reaction (RT-PCR). The expression of TLR2 and TLR4 in peritoneal cells was measured by flow cytometry. RESULTS: Streptococcal protein significantly enhanced the activities of proliferation and phagocytosis of macrophages (P<0.05), induced the release of IL-6, TNF-alpha and the expression of IL-6, TNF-alpha mRNA (P<0.05).The streptococcal protein, meanwhile, also up-regulated the expression of TLR2 and TLR4 in macrophages in vitro (P<0.05). CONCLUSION: Streptococcal protein may promote proliferation, phagocytosis and cytokines production in regulation of the activity of murine macrophages.