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In this study, a fluorescent probe (GMP-Tb-SSA) utilizing lanthanide coordination polymer nanoparticles, GMP-Tb, as a sensing platform, and 5-sulfosalicylic acid (SSA) as a cofactor ligand was proposed for the detection of copper ions (Cu2+). GMP-Tb was synthesized by the self-assembly of guanine monophosphate (GMP) and terbium ion (Tb3+), and SSA was introduced as a sensitizer into the GMP-Tb network. Cu2+ could efficiently inhibit the electron transfer from the ligand GMP to the central ion, Tb3+, leading to a significant quench of fluorescence of Tb3+. The method is highly selective with a linear range of 0 to 21 µM and a detection limit of 300 nM. It is not interfered by metal ions, amino acids, and other species, and can be successfully applied to the detection of Cu2+ in real water samples.
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As an effective ingredient of disinfectants, ClO- inevitably remains in water, which induces potential health hazards such as lung damage and kidney disease. In this study, we synthesized stimulus-responsive dual-ligand luminol-Tb-GMP coordination polymer nanoparticles (luminol-Tb-GMP CPNPs) as highly selective fluorescent probes for the real-time and visual detection of ClO- . CPNPs consist of Tb3+ , a nuclear metal, that coordinates with GMP and luminol, an auxiliary ligand. GMP can be oxidized by ClO- and damage its structure, resulting in fluorescence quenching of CPNPs. The two-ligand CPNPs sensor has a rapid fluorescent response, significant fluorescent color change, and high sensitivity, with a linear range of 2-18 µM and a detection limit of 0.14 µM. It has been successfully used to detect ClO- in tap water, fountain water, and drinking water. Simultaneously, the portable filter paper strip was prepared to expand the range of applications outside the laboratory, which will provide a promising application for the real-time and semiquantitative analysis of ClO- .
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Água Potável , Corantes Fluorescentes , Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Espectrometria de Fluorescência/métodos , Ligantes , Luminol/análise , Água Potável/análiseRESUMO
Thorium, as an important radioactive element, is widely present in nature, and its accompanying environmental pollution is also serious. Extracellular polymeric substances (EPS) are commonly found on the surface of microbial bodies and have strong adsorption capacity for metal ions. In this study, four methods were used to extract EPS from indigenous bacteria of rare earth tailings and to determine the best extraction method. The extracted EPS was applied to treat Th4+, and the changes in functional groups and composition of EPS were investigated. The results showed that the ultrasonic method was more efficient than other methods. The best removal efficiency was observed at pH 3.5, Th4+ concentration of 20 mg/L, and EPS dosage of 30 mL at 25 °C. After 9 h, the adsorption process reached equilibrium with a maximum removal efficiency of 75.93% and a maximum theoretical adsorption capacity of 25.96 mg/g. The Th4+ removal process was consistent with the Langmuir and Freundlich adsorption isotherms and the kinetic data were consistent with the pseudo-second-order kinetic model, which is mainly based on chemisorption. Amide I and amide II of proteins, C-H from aliphatic, as well as O-H and C = O from carboxylic acid play important roles in the adsorption process.
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Matriz Extracelular de Substâncias Poliméricas , Tório , Tório/análise , Tório/metabolismo , Matriz Extracelular de Substâncias Poliméricas/química , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Bactérias , Íons/análise , AdsorçãoRESUMO
Dermatophytosis is an intractable superficial fungal infection of keratinized structures, with approximately 20% incidence in humans. Alterations of keratinocytes in the pathogenesis of dermatophytosis at the transcriptome level remain unclear. To understand and characterize such responses, keratinocytes were infected with Trichophyton mentagrophytes. After infection with 1 × 105 conidia/mL T. mentagrophytes for 24 h, the adherence of fungal hyphae to keratinocytes and the damage caused to cell morphology and structure were observed by light microscopy and transmission electron microscopy, respectively. Levels of pro-inflammatory cytokines IL-1α, IL-1ß, TNFα, and IL-8 significantly increased after infection. RNA-seq and bioinformatic analyses revealed that 766 genes were significantly whereas 2207 genes were repressed in the T. mentagrophyte-infected cells. Some of the differentially expressed genes (DEGs) were related to inflammation, immune responses, wound healing, metabolism, and oxidative stress. GO and KEGG pathway enrichment analyses revealed that DEGs and pathways involved in inflammatory response, immune response, and pathogen-induced dysfunction were significantly enriched in the infected cells. Furthermore, gene set enrichment analysis revealed that higher expression gene sets were mainly involved in immune responses, whereas lower expression gene sets were related to cell component organization or biogenesis and transporter activity. Furthermore, protein-protein interaction network and function analyses revealed that JUN, TP53, FOS, MYC, and HSP90AA1 play a key role in immune responses. Overall, our study systematically uncovered the transcriptome-level response of keratinocytes to T. mentagrophyte and provided insights into dermatophytosis treatment.
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Dermatomicoses , Tinha , Biologia Computacional , Dermatomicoses/microbiologia , Perfilação da Expressão Gênica , Humanos , Queratinócitos , Tinha/genética , Tinha/microbiologia , Transcriptoma , Trichophyton/genéticaRESUMO
With the widely application of liquid biopsy and the development of detection technology, the standardization of pre-analysis procedures is necessary. For controlling pre-analysis variation of circulating tumor DNA (ctDNA) in blood samples, the blood collection tubes for ctDNA preservation particularly contribute a lot. The objective of this study was to investigate whether ImproGene® Cell Free DNA Tube (ImproGene tube) can be used in sample collection, preservation and NGS based mutation detection for ctDNA. We investigated hemolysis and cell free DNA (cfDNA) concentration of blood samples stored in ImproGene tubes and detected ß-actin, LINE1 and exogenous gene level by qPCR. We compared cfDNA and RNA quantity between samples in ImproGene tube and Streck Cell-Free DNA BCT® (Streck tube). And 10 gene mutations and three fusion mutations analysis were compared by sequencing. When stored at room temperature within 7 days in ImproGene tubes, blood samples had no visible hemolysis and the cfDNA concentration, levels of ß-actin, LINE1 and exogenous gene remained stable which means no genomic DNA release and cfDNA was protected. There was no significant difference in cfDNA and RNA quantity between ImproGene tubes and Streck tubes. Furthermore, based on this limited data set, ImproGene tubes showed increased detection rates of low-level mutations. Therefore, ImproGene Cell Free DNA Tubes may have promising applications in sample collection, preservation and NGS based mutation detection for ctDNA by its good preservation performance.
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Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias , Actinas/genética , Ácidos Nucleicos Livres/genética , Hemólise , Humanos , Mutação , Neoplasias/genética , RNARESUMO
BACKGROUND: With the development of liquid biopsy technology, the demand for noninvasive prenatal testing (NIPT) is increasing rapidly. The aim of the study is to evaluate the effects of different blood collection tubes on plasma cfDNA and NIPT quality control. METHODS: We investigated hemolysis, cfDNA concentration, and fragment distribution within blood samples stored in EDTA, ImproGene, and Streck tubes. The effects of ImproGene and Streck tubes on NIPT quality control were evaluated. RESULTS: The ImproGene tubes prevented the time-dependent increase of cfDNA concentration and preserved the cfDNA fragment size distribution. For NIPT quality control, there is no significant difference in cfDNA, library concentration, and fetal fraction between ImproGene and Streck tubes samples. GC content of the samples in ImproGene tubes was closer to the human genome. CONCLUSION: The ImproGene cfDNA tube has excellent performance and is an effective choice for storing blood samples for NIPT testing or other cfDNA analysis.
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Ácidos Nucleicos Livres , Coleta de Amostras Sanguíneas , Ácidos Nucleicos Livres/genética , Ácido Edético , Feminino , Feto , Hemólise , Humanos , GravidezRESUMO
Diabetic nephropathy is a common kidney condition in patients with diabetes mellitus, which can result in renal failure. Pyroptosis, the process of pro-inflammatory programmed cell death, plays an important role in the pathogenesis of this disease. Long non-coding RNA MALAT1 has also been shown to be involved in diabetic nephropathy. Here, we investigated the role of MALAT1 and the microRNA miR-23c and its target gene ELAVL1 in renal tubular epithelial cells. Our data demonstrated that MALAT1 expression was substantially increased but miR-23c was decreased in streptozotocin-induced diabetic rats and in high-glucose-treated HK-2 cells. Downregulation of MALAT1 or upregulation the expression of miR-23c inhibited pyroptosis in HK-2 cells. In an effort to understand the signaling mechanisms underlying the pro-pyroptotic properties of MALAT1 and the anti-pyroptotic properties of miR-23c, we found that inhibiting the expression of MALAT1 downregulated the expression of ELAVL1, NLRP3, Caspase-1 and the pro-inflammatory cytokine IL-1ß. These findings were replicated by upregulation of miR-23c. Moreover, luciferase assays showed that miR-23c, as a target of MALAT1, directly repressed ELAVL1 expression and then decreased the expression of its downstream protein NLRP3. The expression of MALAT1 antagonized the effect of miR-23c on the downregulation of its target ELAVL1 and inhibited hyperglycemia-induced cell pyroptosis. This mechanism may contribute to a better understanding of diabetic nephropathy pathogenesis and facilitate the development of new therapeutic strategies for the treatment of this disease.
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Nefropatias Diabéticas/metabolismo , Proteína Semelhante a ELAV 1/genética , MicroRNAs/genética , Piroptose , RNA Longo não Codificante/genética , Animais , Caspase 1/genética , Caspase 1/metabolismo , Linhagem Celular , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Proteína Semelhante a ELAV 1/metabolismo , Células Epiteliais/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Túbulos Renais/citologia , Túbulos Renais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Shrinkage cracks are some of the most common defects in timber structures obtained from woods with an uneven distribution of moisture content and are subject to external dynamic environmental changes. To accurately predict the changes in the moisture content of wood components at any time and position, this study first applied the principles of food drying and established a moisture field model for laminated wood based on the analogy between heat and humidity transfer. A model for predicting the moisture content of wood that considers time and spatial distribution was then proposed. Second, by collecting relevant experimental data and establishing a finite element analysis model, three moisture absorption conditions (0-9.95%, 0-13.65%, and 0-17.91%) and four desorption conditions (34-5.5%, 28-8.3%, 31-11.8%, and 25.5-15.9%) were analyzed. In the moisture absorption comparison, the time needed to reach 95% equilibrium moisture content was 2.43 days, 4.07 days, and 6.32 days. The rate at which the internal components reached equilibrium moisture content exceeded 10 days. The temporal and spatial distribution of wood moisture content revealed the correctness of the proposed wood moisture field model. Finally, the moisture content prediction model was applied in the order of characteristic equation solutions, moisture content gradient difference, and laminated wood size. The results revealed that the established humidity field model can predict the wood moisture content and how it changes over time and in space. Notably, 1-2 orders for the solution of the characteristic equation are recommended when applying the prediction model. The greater the difference in moisture content, the faster the equilibrium moisture content is reached. The moisture content varies greatly based on the component size and position. Notably, the influence of moisture gradient and wood size on the average wood moisture content cannot be ignored.
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OBJECTIVE: Cerebral microbleeds (CMBs) are punctate hemorrhagic lesions within the brain parenchyma and are a classic manifestation of cerebral small vessel disease (CSVD). The primary objective of this study is to investigate the potential role of miR-4685-3p and underlying mechanisms by which miR-4685-3p modulates matrix metalloproteinase-9 (MMP9) in cerebral microvascular endothelial cell injury. METHODS: We employed high-throughput sequencing to screen for differentially expressed miRNAs in the peripheral blood of patients with CMBs and healthy controls. Employing lipopolysaccharide (LPS) to induce cellular damage, we aim to establish a model of human brain microvascular endothelial cells (hCMEC/D3) injury. We also had cells transfected with miR-4685-3p mimic and MMP9 overexpression plasmid. We utilized quantitative polymerase chain reaction (qPCR) to assess the expression levels of miR-4685-3p and performed Western blot analysis to examine MMP9 expression levels in the cells. We employed the CCK-8 assay, TUNEL assay, and tube formation assay to evaluate cellular viability, apoptotic rates, and angiogenic capabilities. Furthermore, dual-luciferase reporter assay analysis was conducted to confirm the relationship between miR-4685-3p and MMP9. RESULTS: The sequencing results indicated a downregulation of miR-4685-3p in the peripheral blood of patients with CMBs. Within the context of LPS-induced injury to hCMEC/D3 cells, miR-4685-3p exhibits reduced expression, whereas MMP9 expression levels are elevated. The elevation of miR-4685-3p expression levels attenuates LPS-induced cellular apoptosis and enhances the viability and tube-forming capacity of hCMEC/D3 cells. Concomitant transfection with MMP9 overexpression constructs effectively reversed the detrimental effects of LPS on hCMEC/D3 cell integrity. We further confirmed that miR-4685-3p overexpression directly targets MMP9, leading to negative regulation of MMP9 expression. CONCLUSION: Upregulating miR-4685-3p, which targets the MMP9 axis, mitigated LPS-induced cerebral microvascular endothelial cell injury, potentially playing a protective role in the progression of CMBs.
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Encéfalo , Células Endoteliais , Metaloproteinase 9 da Matriz , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Células Endoteliais/metabolismo , Encéfalo/patologia , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Masculino , Apoptose/genética , Microvasos/patologia , Lipopolissacarídeos/farmacologia , Hemorragia Cerebral/genética , Hemorragia Cerebral/patologia , Hemorragia Cerebral/metabolismo , Feminino , Pessoa de Meia-Idade , Linhagem CelularRESUMO
The transformation of social development modes has led to profound changes in the pattern of intangible cultural heritage, while simultaneously posing significant challenges to its preservation. The rapid development of artificial intelligence (AI) technology has brought new development opportunities in various research fields. This study intends, by constructing and evaluating a theoretical model, to investigate whether AI-generated cultural and creative products can promote the sustainability of intangible cultural heritage. The central focus of this research is to measure the effectiveness of AI technologies in promoting the sustainability of intangible cultural heritage. The context of the research design is rooted in the attention, interest, search, action, and share (AISAS) model, incorporating theories of perceived value and cultural identity, to forecast the long-term viability of AI-generated cultural and creative products in the promotion of intangible cultural heritage. This research was conducted in Tianjin, China and carried out using quantitative methods, a questionnaire survey, and the accidental sampling method, taking a sample of 291 participants for analysis. The results show that 1) the attraction of and interest and participation in AI-generated Yangliuqing New Year Print cultural and creative products have a positive effect on perceived value; 2) the purchase and sharing of these products have a positive impact on cultural identity; 3) the perceived value has a positive impact on cultural identity; and 4) cultural identity has a positive impact on the sustainability of intangible cultural heritage. This study contributes to the theoretical development and practical application of the AISAS model and offers valuable insights into the future development trajectory of intangible cultural heritage, thereby promoting its sustainability. The limitations of this study are its small sample size and geographical restrictions. In future studies, the sample size will be expanded and will include more regions for data analysis.
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OBJECTIVE: This study aimed to investigate the effects of Shiquan Dabu Tang (SDT) on growth and angiogenesis of subcutaneously implanted tumors, hepatic metastases, and incision-implanted tumors after surgical removal of primary colon tumor in mice. METHODS: Three experimental models were built after surgical removal of primary colon tumor and the mice were randomly divided into three groups: primary tumor resection (TR) group, primary tumor-preserved (TP) group and SDT group. After resection of the primary tumor and SDT treatment for 10 d, levels of vascular endothelial growth factor (VEGF), angiostatin (AS) and endostatin (ES) were examined by enzyme-linked immunosorbent assay (ELISA); microvascular density (MVD) and cell proliferation of metastasis were detected by streptavidin-peroxidase immunohistochemical staining; tumor cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assay. RESULTS: In the subcutaneously implanted tumor model, the average volume of metastases of the SDT group was significantly lower than that of the TR group (P<0.01); the incidence rate of metastases was 50%. In the hepatic metastases model, the average number of hepatic metastases nodules of the SDT group was significantly lower than that of the TR group (P<0.01); the incidence rate of metastases was 40%. In the incision-implanted tumor model, the average volume of metastases of the SDT group was significantly lower than that of the TR group; the incidence rate of metastases was 30%. MVD was significantly inhibited by SDT and Ki67 expression of the SDT group was significantly lower than that of the TR group (P<0.01). TUNEL apoptotic index of tumor of the SDT group was higher than that of the TR group (P<0.01). ELISA showed that the serum VEGF level was significantly decreased and the serum ES level was significantly increased in the SDT group compared with those in the TR group (P<0.01). CONCLUSION: Resection of primary tumor in mice causes imbalance of VEGF, AS and ES, thus promoting angiogenesis and metastasis of tumors. SDT can inhibit growth, angiogenesis and cell proliferation of the metastatic tumor and promote cell apoptosis after surgical removal of the primary tumors.
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Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Linhagem Celular Tumoral , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Neovascularização Patológica , FitoterapiaRESUMO
Introduction: As a representation of the gut microbiota, fecal and cecal samples are most often used in human and animal studies, including in non-alcoholic fatty liver disease (NAFLD) research. However, due to the regional structure and function of intestinal microbiota, whether it is representative to use cecal or fecal contents to study intestinal microbiota in the study of NAFLD remains to be shown. Methods: The NAFLD mouse model was established by high-fat diet induction, and the contents of the jejunum, ileum, cecum, and colon (formed fecal balls) were collected for 16S rRNA gene analysis. Results: Compared with normal mice, the diversity and the relative abundance of major bacteria and functional genes of the ileum, cecum and colon were significantly changed, but not in the jejunum. In NAFLD mice, the variation characteristics of microbiota in the cecum and colon (feces) were similar. However, the variation characteristics of intestinal microbiota in the ileum and large intestine segments (cecum and colon) were quite different. Discussion: Therefore, the study results of cecal and colonic (fecal) microbiota cannot completely represent the results of jejunal and ileal microbiota.
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[This corrects the article DOI: 10.3389/fcimb.2022.870785.].
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In recent years, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in the world. As an important model animal, the characteristics of gut microbiota alteration in mice with NAFLD have been studied but the changes in metabolite abundance in NAFLD mice and how the gut microbiota affects these intestinal metabolites remain unclear. In this experiment, a mouse model for NAFLD was established by a high-fat diet. The use of 16S rDNA technology showed that while there were no significant changes in the alpha diversity in the cecum of NAFLD mice, the beta diversity changed significantly. The abundance of Blautia, Unidentified-Lachnospiraceae, Romboutsia, Faecalibaculum, and Ileibacterium increased significantly in NAFLD mice, while Allobaculum and Enterorhabdus decreased significantly. Amino acids, lipids, bile acids and nucleotide metabolites were among the 167 significantly different metabolites selected. The metabolic pathways of amino acids, SFAs, and bile acids were significantly enhanced, while the metabolic pathways of PUFAs, vitamins, and nucleotides were significantly inhibited. Through correlation and MIMOSA2 analysis, it is suggested that gut microbiota does not affect the changes of lipids and bile acids but can reduce thiamine, pyridoxine, and promote L-phenylalanine and tyramine production. The findings of this study will help us to better understand the relationship between gut microbiota and metabolites in NAFLD.
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Microbiota , Hepatopatia Gordurosa não Alcoólica , Aminoácidos/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Lipídeos , Fígado/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologiaRESUMO
The members of the family Iridoviridae are large, double-stranded DNA viruses that infect various hosts, including both vertebrates and invertebrates. Although great progress has been made in genomic and phylogenetic analyses, the adequacy of the existing criteria for classification within the Iridoviridae family remains unknown. In this study, we redetermined 23 Iridoviridae core genes by re-annotation, core-pan analysis and local BLASTN search. The phylogenetic tree based on the 23 re-annotated core genes (Maximum Likelihood, ML-Tree) and amino acid sequences (composition vector, CV-Tree) were found to be consistent with previous reports. Furthermore, the information provided by synteny analysis and codon usage preference (relative synonymous codon usage, correspondence analysis, ENC-plot and Neutrality plot) also supports the phylogenetic relationship. Collectively, our results will be conducive to understanding the genera demarcation within the Iridoviridae family based on genomic synteny and component (codon usage preference) and contribute to the existing taxonomy methods for the Iridoviridae family.
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Ranaviruses can infect both captive and wild cold-blooded vertebrates, leading to significant economic and environmental losses. With the cases of ranavirus infection increasing, many ranavirus genomic sequences were published, but little is known about ranavirus taxonomy on a whole-genome level. In this study, 44 ranaviruses core genes were identified in 32 ranaviruses genome sequences by using PanX. The neighbour-joining phylogenetic trees (NJ-tree) based on 44 ranaviruses core genes and 24 iridoviridae core genes and composition vector phylogenetic tree (CV-Tree) based on whole genome were constructed. The three of phylogenetic trees showed that 32 ranavirus isolates can be divided into 4 different subgroups including SGIV-like, EHNV-like, FV3-like and CMTV-like, and subgroups taxonomic position of three phylogenetic trees were consistent. However, the phylogenetic position of ToRV could not be determined if it belongs to FV3-like or CMTV-like group. Subsequently, we carried out dot plot analysis and confirmed that ToRV should belong to CMTV-like group. Based on dot plot analysis and phylogenetic trees, the taxonomic classification of ranaviruses was confirmed. Finally, four genes which are suitable for the construction of phylogenetic tree were selected from ranavirus core genes by recombination analysis, substitution saturation analysis and single-gene phylogenetic analysis. Phylogenetic tree based on concatenated sequences of the four selected genes showed that the classification of subgroups was identical with three of the phylogenetic trees. Conclusion: Our results confirmed taxonomic identification of ranaviruses; the four selected genes used in phylogenetic analysis will make taxonomic identification more convenient and accurate.
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Infecções por Vírus de DNA , Ranavirus , Anfíbios , Animais , Infecções por Vírus de DNA/epidemiologia , Infecções por Vírus de DNA/veterinária , Genômica , Filogenia , Ranavirus/genéticaRESUMO
Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.
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Coreia/diagnóstico , Coreia/terapia , China , Coreia/genética , Consenso , Distonia/diagnóstico , Distonia/genética , Distonia/terapia , Humanos , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genéticaRESUMO
Ischemic stroke is a serious threat to human life and health, which is often accompanied by cerebral ischemia-reperfusion (I/R) injury in clinic. Ischemic postconditioning (IPostC) is a short period of mild non-fatal ischemia in the early stage of cerebral I/R injury. However, there are few reports about the protective effect of IPostC. In the present study, we investigated the neuroprotective effect of IPostC in a mice model of ischemia induced by the middle cerebral artery occlusion (MCAO). MicroRNA-124(miR-124) is a small RNA highly expressed in the brain. Several studies have shown that miR-124 is significantly decreased in IPostC. Therefore, we hypothesize that IPostC may play an important role by downregulating the expression of miR-124. Mice were treated with cerebral I/R and IPostC treatment on the basis of MCAO. The results showed that IPostC significantly reduced neurobehavioral deficits and decreased brain infarct volume. Moreover, we also found that inhibiting miR-124 effectively reduced neurons/cells apoptosis in vivo and vitro. In addition, western blot analysis of apoptosis-related proteins and PI3K/Akt2 signaling pathway proteins showed that downregulation of miR-124 significantly decreased the expression of Caspase-3 and BAX, and increased the expression of anti-apoptotic protein Bcl-2. Inhibition of miR-124 also increase PI3K/Akt/mTOR signaling pathway, thus inhibiting cell apoptosis and autophagy. However, overexpression of miR-124 weakens the protective effect of IPostC. These observations suggest that IPostC exerts its neuroprotective effect through negatively regulating PI3K/Akt2 signaling pathway by miR-124.
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Infarto Cerebral/patologia , Pós-Condicionamento Isquêmico , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose , Regulação para Baixo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Neurônios , Células PC12 , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Transdução de SinaisRESUMO
Meteorological conditions, gas-phase precursors, and aerosol acidity (pH) can influence the formation of secondary inorganic aerosols (SIA) in fine particulate matter (PM2.5). Most works related to the influence of pH and gas-phase precursors on SIA have been laboratory research, but field observation research is very scarce, especially in arid environments. The relationship among SIA, pH, gas-phase precursors, and meteorological conditions are investigated in Hohhot, a major city in China with an arid environment. Secondary inorganic species, e.g., SO42-, NO3-, were typically found at low levels, reflecting the low level of secondary aerosol. It is interesting to note that the level of SO2 in Hohhot was higher than in other cities while SO42- was relatively lower than in other cities. Multiple receptor models were used to explore the contributions to the SIA and quantify the source impacts on the SIA. Annual average aerosol pH in Hohhot was 5.6 (range 1.1-8.4) which was estimated by a thermodynamic equilibrium model. Additionally, a statistical method was used to evaluate the influence of SIA sources on ambient aerosol concentrations. Aerosol water content and particulate acidity were found to be positively associated with secondary SO42-, while NO2 and RH had a significant impact on secondary NO3- in an arid atmosphere. The findings explain the relationship between gaseous precursors, relative humidity, aerosol pH and temperature in the arid city of Hohhot.