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Visible light-enhanced [3 + 2] cycloaddition of N,N-disubstituted hydrazines with N-cyano-N-aryl-p-toluenesulfonamides is an efficient reaction pathway to polysubstituted 1,2,4-triazol-3-amines. The reaction is performed under mild conditions without the addition of any transition metals. This strategy involves a C(sp3)-H bond activation, a cyano cycloaddition, and the formation of two new CâN bonds. The protocol shows the advantages of good functional group tolerance and broad substrate scope. The late-stage modification experiments provide practical applications in the field of organic synthesis and medicinal chemistry.
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A copper-promoted aerobic oxidative [3+2] cycloaddition reaction for the synthesis of various substituted pyrazoles from N,N-disubstituted hydrazines with alkynoates in the presence of bases is developed. This work involves a direct C(sp3)-H functionalization and the formation of new C-C/C-N bonds. In this strategy, inexpensive and easily available Cu2O serves as the promoter and air acts as the green oxidant. The reaction exhibits the advantages of high atom and step economy, high regioselectivity, and easy operation.
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A facile and efficient catalyst-/metal-/oxidant-free DBU-promoted deaminative thiolation reaction of 1H-benzo[d]imidazol-2-amines and benzo[d]oxazol-2-amines has been developed at room temperature conditions in a one-pot protocol. This practical three-component strategy represents a novel and environmentally friendly reaction pathway toward the straightforward synthesis of various 2-thio-1H-benzo[d]imidazoles and 2-thiobenzo[d]oxazoles using carbon disulfide as a sulfur source through C-N bond cleavage and C-S bond formation process. Different types of 1H-benzo[d]imidazol-2-amines, benzo[d]oxazol-2-amines, and organic bromides are suitable substrates. The gram-scale and late-stage modification experiments provide the potential applications based on this methodology in the field of organic and medicinal chemistry.
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BACKGROUND: Amelogenesis imperfecta (AI) is a developmental enamel defect affecting the structure of enamel, esthetic appearance, and the tooth masticatory function. Gene mutations are reported to be relevant to AI. However, the mechanism underlying AI caused by different mutations is still unclear. This study aimed to reveal the molecular pathogenesis in AI families with 2 novel pre-mRNA splicing mutations. METHODS: Two Chinese families with AI were recruited. Whole-exome sequencing and Sanger sequencing were performed to identify mutations in candidate genes. Minigene splicing assays were performed to analyze the mutation effects on mRNA splicing alteration. Furthermore, three-dimensional structures of mutant proteins were predicted by AlphaFold2 to evaluate the detrimental effect. RESULTS: The affected enamel in family 1 was thin, rough, and stained, which was diagnosed as hypoplastic-hypomature AI. Genomic analysis revealed a novel splicing mutation (NM_001142.2: c.570 + 1G > A) in the intron 6 of amelogenin (AMELX) gene in family 1, resulting in a partial intron 6 retention effect. The proband in family 2 exhibited a typical hypoplastic AI, and the splicing mutation (NM_031889.2: c.123 + 4 A > G) in the intron 4 of enamelin (ENAM) gene was observed in the proband and her father. This mutation led to exon 4 skipping. The predicted structures showed that there were obvious differences in the mutation proteins compared with wild type, leading to impaired function of mutant proteins. CONCLUSIONS: In this study, we identified two new splicing mutations in AMELX and ENAM genes, which cause hypoplastic-hypomature and hypoplastic AI, respectively. These results expand the spectrum of genes causing AI and broaden our understanding of molecular genetic pathology of enamel formation.
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Amelogênese Imperfeita , Proteínas do Esmalte Dentário , Humanos , Feminino , Amelogenina/genética , Amelogênese Imperfeita/genética , Proteínas do Esmalte Dentário/genética , Proteínas do Esmalte Dentário/metabolismo , Mutação/genética , Proteínas Mutantes/genética , Proteínas da Matriz Extracelular/genéticaRESUMO
A facile access to benzo[d]thiazole-2(3H)-thiones and benzo[d]thiazol-2(3H)-ones has been developed through a temperature-controlled intermolecular [3 + 2] annulation of N,N-disubstituted arylhydrazines with CS2 in the presence of DMSO. This protocol can obviate the prefunctionalization of the starting materials. This direct C-S/C-N bond formation reaction was performed in the absence of any external catalysts, transition metals, bases, ligands, and oxidants with high step economy.
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Tionas , Elementos de Transição , Metais , Temperatura , Tiazóis/química , Tionas/químicaRESUMO
An efficient copper-catalyzed aerobic oxidative cross-dehydrogenative coupling reaction for the synthesis of multisubstituted phosphorylhydrazides from N,N-disubstituted hydrazines and hydrogen phosphoryl compounds is accomplished. The reaction proceeds under mild conditions without the addition of any external oxidants and bases. This work reported here represents a direct P(âO)-N-N bond formation with the advantages of being operationally simple, good functional group tolerance, and high atom and step economy. Furthermore, the selected compounds exhibit potential inhibitory activity against tumor cells, which can be used in the field of screening of anticancer agents as new chemical entities.
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Antineoplásicos , Hidrazinas , Antineoplásicos/farmacologia , Catálise , Cobre/química , Hidrazinas/química , Hidrazinas/farmacologia , FosforilaçãoRESUMO
A new photocatalyst-free visible-light-enhanced strategy for the synthesis of pyrazolo[1,5-a][1,3,5]triazine-2,4-diamines via the formation of electron donor-acceptor (EDA) complexes is reported. The in situ generated pyrazolthiourea intermediates from 1H-pyrazol-3-amines and isothiocyanates undergo formal [4 + 2] annulation with 1,1,3,3-tetramethylguanidines (TMG) to deliver the corresponding products involved in three C-N bond formations in a one-pot protocol. The formation of EDA complex from pyrazolthiourea and TMG is confirmed by UV-vis spectroscopy and 1H NMR experiments. Moreover, this mild reaction proceeds in the absence of any external transition metals, oxidants, bases, and ligands. This efficient methodology for the synthesis of purine analogues pyrazolo[1,5-a][1,3,5]triazine-2,4-diamines provides potential synthetic applications in the field of drug research and development.
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Diaminas , Triazinas , Aminas , Luz , PurinasRESUMO
A metal- and oxidant-free three-component desulfurization and deamination condensation of amidines, isothiocyanates, and hydrazines for the synthesis of structurally diverse fully substituted 1H-1,2,4-triazol-3-amines is described. The reaction proceeds without the requirement of any external catalysts, metals, ligands, or oxidants. This [2 + 1 + 2] cyclization strategy involves C-N and C-S bond cleavage and the formation of new C-N bonds in one pot. This transformation provides a series of full substituted 1H-1,2,4-triazol-3-amines with advantages of a broad substrates scope, mild reaction conditions, environmental friendliness, and easy gram-scale applications. The fluorescence and aggregation-induced emission (AIE) properties of selected products were further tested. These synthesized 1H-1,2,4-triazol-3-amines may be worth investigating for further applications in the fields of organic chemistry, medicinal chemistry, and optical materials.
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BACKGROUND AND OBJECTIVE: This study was designed to investigate the p38 mitogen-activated protein kinase (MAPK) signaling pathway involved in Aquaporin1 (AQP1) expression caused by staphylococcal peptidoglycan (PGN) in cultured rat pleural mesothelial cells (rPMCs) in vitro. METHODS: RT-PCR and immunoblot analysis were used to determine the relative mRNA and protein levels of AQP1 by PGN in rPMCs. P38 kinase inhibitor SB203580, JNK inhibitor SP600125, and ERK1/2 inhibitor PD98059 were used to determine the effects of PGN-induced AQP1 expression by immunoblot. Activation of p38 by PGN was reflected by detecting the phosphorylation constituent of p38, using immunoblot. The shift of localization after activation of p38 by PGN was investigated by immunofluorescence assay. RESULTS: AQP1 transcription and protein expression were decreased by PGN in dose-dependent and time-dependent manners in rPMCs. Down-regulation of AQP1 by PGN was blocked only by SB203580, neither by SP600125 nor by PD98059. Furthermore, rPMCs exposed to PGN showed activation of p38 MAPK. Phospho-p38 protein production was increased by PGN stimulation in rPMCs. The localization of phospho-p38 was both in the cytosol and nuclei after PGN treatment, while its normal distribution is mainly in the cytosol in rPMCs. CONCLUSION: AQP1 expression was decreased by PGN in both dose-dependent and time-dependent manners in rPMCs. This down-regulation by PGN-induced AQP1 in rPMCs may be mediated by the activation of p38 MARK pathway.
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Aquaporina 1/metabolismo , Sistema de Sinalização das MAP Quinases , Pleura/metabolismo , Animais , Células Cultivadas , Regulação para Baixo , Células Epiteliais/metabolismo , Masculino , Peptidoglicano , Fosforilação , Ratos Wistar , Staphylococcus aureusRESUMO
OBJECTIVE: To establish model of dental pulp cells with activated Notch signaling pathway, and investigate the effect of activating Notch signaling pathway on senescence of human dental pulp cells in vitro. METHODS: Human dental pulp cells were isolated, cultured as usual, and used from the 4(th) passage. The cells were divided into the activated group and the negative control group. In the activated group, the way of coating dishes with Jagged1 protein (10 mg/L) was used to activate Notch signaling pathway. The negative control group cells received no treatment. In the 4(th), 8(th), and 10(th) passages, the expression levels of the Notch signaling pathway downstream gene Hes1 were verified by real-time quantitative PCR (RT-qPCR). The cell changes after activating Notch signaling pathway were observed at three levels: (1) The cell morphology changes were observed through invert phase contrast microscope. The cell activity was detected with MTT assay. (2) The alkaline phosphatase (ALP) expression and its activity, and senescence-associated &bgr;-galatosidase (SA-ß-Gal) expression were observed with the kit. (3) The expression changes of senescence related genes were verified using RT-qPCR. The difference between the negative control group and the activated group was analyzed using student's t test. RESULTS: The expression level of the downstream gene Hes1 of Notch signaling pathway increased after coating the dishes with Jagged1 protein, indicating the establishment of the model of dental pulp cells with activated Notch signaling pathway. Compared with the negative control group, the aging cells of the activated group appeared relatively late. In the 8(th) and 10(th) passage, the cell activity increased. In the 10th passage, ALP activity increased, but SA-ß-Gal expression decreased. p16 gene expression decreased in each passage, and p53 gene expression decreased in the 8(th) and 10(th) passages. CONCLUSION: Jagged1 could activate Notch signaling pathway effectively. Through activating Notch signaling pathway, the dental pulp cells showed a trend of senescence delay at different levels, such as cell morphology, metabolic enzyme expressions and related gene expressions.
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Senescência Celular , Polpa Dentária/citologia , Células Epiteliais/metabolismo , Receptores Notch/fisiologia , Transdução de Sinais , Proteínas de Ligação ao Cálcio/metabolismo , Células Cultivadas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-1 , Proteínas de Membrana/metabolismo , Proteínas Serrate-JaggedRESUMO
OBJECTIVE: To evaluate the effects of Jidesheng anti-venom used externally for skin and soft-tissue necrosis from Chinese cobra bite. METHODS: A retrospective review was performed according to the clinical data recorded from January 2002 to December 2012. A total of 126 patients (116 females and 10 males) with skin and soft-tissue necrosis due to Chinese cobra bite were divided into two groups. The control group was treated externally with 40% glyceride magnesium sulfate (n = 52), and the treatment group was given Jidesheng anti-venom externally (n = 74). The data collected included maximum local necrotic area of skin and soft tissues, de-tumescence time, healing time, and skin-grafting rate. RESULTS: There were no significant differences in gender, age, and disease condition between the control and treatment groups (P > 0.05). No statistically significant difference was found in de-tumescence time between the two groups (P > 0.05). The maximum local necrotic area of skin and soft tissues was (19.9 +/- 7.3) cm2 in the treatment group, while it was (23.3 +/- 6.4) cm2 in the control group. The healing time of the treatment group was shorter than that of the control group [(32.1 +/- 3.7) vs (34.4 +/- 4.5) days)]. The skin-grafting rate in the treatment group was lower than that of the control group (10.81% vs 25.00%). There were statistically significant differences in maximum local necrotic area of skin and soft tissues, healing time, and skin-grafting rate between the control and treatment groups (all P < 0.05). CONCLUSION: External application of Jidesheng anti-venom may help to promote wound healing and reduce the skin-grafting rate in cases of skin and soft-tissue necrosis due to Chinese cobra bite.
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Medicamentos de Ervas Chinesas/administração & dosagem , Venenos Elapídicos/antagonistas & inibidores , Mordeduras de Serpentes/tratamento farmacológico , Lesões dos Tecidos Moles/tratamento farmacológico , Administração Cutânea , Animais , Venenos Elapídicos/toxicidade , Elapidae , Feminino , Humanos , Masculino , Necrose , Estudos Retrospectivos , Pele/efeitos dos fármacos , Pele/patologia , Mordeduras de Serpentes/patologia , Lesões dos Tecidos Moles/patologiaRESUMO
OBJECTIVE: This study aimed to evaluate the long-term clinical performance of Giomer and a self-etch adhesive system compared with a nanofilled resin composite and etch-and-rinse adhesive system in Class I and Class II restorations. METHOD: The study was designed to be double-blinded with intra-individual control. 48 patients with 54 pairs of cavities (class I or class II) were recruited. Each pair of restorations was placed with either BEAUTIFIL II (BF) and FL-BOND II (FL) or Filtek Z350 (Z350) and Scotchbond Multi-Purpose (SMP). Clinical evaluation was performed at baseline, 6-month, 18-month, 4-year and 8-year after placement according to modified USPHS criteria. Kaplan-Meier survival analysis and log rank tests were performed (SPSS 20.0, IBM Corporation, US) to compare the survival probability of different restorations.A generalized linear mixed model (GLMM) was adopted to assess the performance of the materials. The McNemar test was used to show significant changes for all the evaluation criteria and difference between them. RESULTS: At the eight-year recall, 32 patients with 67 restorations were present. There were twelve restorations in total recorded as failure due to loss of retention, restoration fracture, secondary caries, tooth fracture or endodontic treatment due to pulp necrosis. The survival probabilities and calculated annual failure rate(AFR) of BF and Z350 restorations at 8-year were 87.2 % vs 87.8 % and 1.6 % vs 1.5 % respectively with no significant difference (p > 0.05)between the two materials. Over the recall time range of eight years, decreased possibility of alpha rating was observed for retention, marginal adaptation, marginal staining and surface roughness for both materials (p < 0.05). Decreased possibility of alpha rating was observed for surface staining and secondary caries for Z350 (p < 0.05) and restoration fracture for BF (p < 0.05), respectively. Comparing the two restorative systems over eight years, no significant difference was seen for linear decline of the possibility of alpha rating for any of the criteria evaluated (p > 0.05). CONCLUSION: Giomer material and the self-etch adhesive system had comparable clinical performance with nanofilled resin composite and etch-and-rinse adhesive system over the observation period of eight years.
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Resinas Compostas , Restauração Dentária Permanente , Cimentos de Resina , Humanos , Resinas Compostas/química , Masculino , Feminino , Método Duplo-Cego , Adulto , Cimentos de Resina/química , Pessoa de Meia-Idade , Cimentos de Ionômeros de Vidro/química , Falha de Restauração Dentária , Cárie Dentária/terapia , Nanocompostos/química , Bis-Fenol A-Glicidil MetacrilatoRESUMO
Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes. Additionally, ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified. Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes. Indeed, clinicians have been aware of these concerns for years. Based on the current evidence of studies, this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions. The evolution of different kinetic irrigation methods, their effects, limitations, the paradigm shift, current indications, and effective operational procedures regarding intracanal medication are also discussed. This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication, thus facilitating a better understanding of infection control, standardizing clinical practice, and ultimately improving the success of endodontic therapy.
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Controle de Infecções , Tratamento do Canal Radicular , ConsensoRESUMO
OBJECTIVE: To explore whether the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT) could inhibit Notch signaling pathway in human dental pulp cells, and its effects on the proliferation ability of the cells. METHODS: Human dental pulp cells were primarily cultured from healthy premolars or wisdom teeth extracted intactly. The γ-secretase inhibitor DAPT (5 µmol/L) was added to the culture medium from passage 4 to the end. The cells of passages 4, 8 and 10 were used as check points in this study. The Real-time RT-PCR and RT2 Profiler PCR Array were applied to analyze the expression changes of Notch signaling pathway downstream genes. And the methyl thiazolyl tetrazolium (MTT) method was used to test the proliferation ability of the cells. RESULTS: After DAPT was added, Hes1 gene expression level decreased significantly in the cells of passages 4, 8 and 10 as compared with that of the same passage cells in the control group. The relative gene expression ratio (experimental/control) decreased to 0.20 in the cells of passage 10, and the difference was significant (t=33.143,P=0.001). The PCR Array results of passage 10 dental pulp cells also showed a decline of Notch signaling pathway downstream genes Hey1 and NR4A2 in the experimental group as compared with the control group. The proliferation of passages 8, and 10 experimental cells were slowed down, and the difference was significant. CONCLUSION: Notch signaling pathway of human dental pulp cells could be inhibited by DAPT effectively. The proliferation of the cells was slowed down by the effect of DAPT, and the normal life cycle of the cells was affected.
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Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Polpa Dentária/citologia , Dipeptídeos/farmacologia , Receptores Notch/metabolismo , Polpa Dentária/efeitos dos fármacos , Humanos , Cultura Primária de Células , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
This research aims to assess the anti-hyperlipidemia effects of alliin in vivo and its potential mechanisms through transcriptomics and metabolomics analysis. A hyperlipidemia mode was established in C57BL/6 mice fed a high-fat diet, and the related physiological parameters of the animals were recorded. Serum TC and MDA in livers significantly decreased by 12.34% and 29.59%, respectively, and SOD and CAT in livers significantly increased by 40.64% and 39.05%, respectively, after high doses of alliin interventions. In total, 148 significantly different genes, particularly Cel, Sqle, Myc, and Ugt1a2, were revealed for their potential roles in HFD-induced alliin, mainly through steroid biosynthesis, triglyceride metabolism, drug metabolism-cytochrome P450, and the PI3K-Akt signaling pathway, according to transcriptomics analysis. Metabolomics results revealed 18 significantly different metabolites between the alliin group and HFD group, which were classified as carboxylic acids, such as N-undecanoylglycine, adipic acid, D-pantothenic acid, cyprodenate, and pivagabine. We found pantothenic acid played a vital role and was effective through pantothenic acid and CoA biosynthesis metabolism. The "steroid biosynthesis pathway" was identified as the most significant metabolic pathway by integrated transcriptomics and metabolomics analysis. This work offered a theoretical framework for the mechanism of alliin lipid lowering in the future. The development and utilization of alliin will be a viable strategy to improve the health status of people with hyperlipidemia, suggesting prospective market opportunities.
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Introduction: Porphyromonas gingivalis and Enterococcus faecalis promote the development of pulpitis and periapical periodontitis. These bacteria are difficult to eliminate from the root canal systems, leading to persistent infection and poor treatment outcomes. We explored the response of human dental pulp stem cells (hDPSCs) to bacterial invasion and the mechanisms underlying the impact of residual bacteria on dental pulp regeneration. Methods: Single-cell sequencing was used to categorize the hDPSCs into clusters based on their response to P. gingivalis and E. faecalis. We depicted a single-cell transcriptome atlas of hDPSCs stimulated by P. gingivalis or E. faecalis. Results: The most differentially expressed genes in the Pg samples were THBS1, COL1A2, CRIM1, and STC1, which are related to matrix formation and mineralization, and HILPDA and PLIN2, which are related to the cellular response to hypoxia. A cell cluster characterized by high expression levels of THBS1 and PTGS2 was increased after P. gingivalis stimulation. Further signaling pathway analysis showed that hDPSCs prevented P. gingivalis infection by regulating the TGF-ß/SMAD, NF-κB, and MAPK/ERK signaling pathways. Differentiation potency and pseudotime trajectory analyses showed that hDPSCs infected by P. gingivalis undergo multidirectional differentiation, particularly to the mineralization-related cell lineage. Furthermore, P. gingivalis can create a hypoxia environment to effect cell differentiation. The Ef samples were characterized by the expression of CCL2, which is related to leukocyte chemotaxis, and ACTA2, which is related to actin. There was an increased proportion of a cell cluster that was similar to myofibroblasts and exhibited significant ACTA2 expression. The presence of E. faecalis promoted the differentiation of hDPSCs into fibroblast-like cells, which highlights the role of fibroblast-like cells and myofibroblasts in tissue repair. Discussion: hDPSCs do not maintain their stem cell status in the presence of P. gingivalis and E. faecalis. They differentiate into mineralization-related cells in the presence of P. gingivalis and into fibroblast-like cells in the presence of E. faecalis. We identified the mechanism underlying the infection of hDPSCs by P. gingivalis and E. faecalis. Our results will improve understanding of the pathogenesis of pulpitis and periapical periodontitis. Furthermore, the presence of residual bacteria can have adverse effects on the outcomes of regenerative endodontic treatment.
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The hypoglycemic effects of konjac glucomannans (KGMs) are well recognized, and our previous study showed KGMs with different molecular weight have different hypoglycemic effects on diabetes rats, but the detailed mechanisms still remain unclear. In this study, KGMs with medium molecular weight (KGM-M, 757.1 kDa) and low molecular weight (KGM-L, 87.3 kDa) were utilized to investigate the possible mechanism on hypoglycemic effects of type 2 diabetic (T2DM) rats. The results revealed that KGM-M had better effects than KGM-L on decreasing fasting blood glucose, mitigating insulin resistance and improving inflammation. Further mechanism analysis showed that KGM-M better enriched gut flora diversity and the abundance of Ruminococcus and Lachnoclostridium, which was accompanied by increased short chain fatty acids (SCFAs) production and expression of G protein-coupled receptors (GPCRs), and improved regulation on bile acid synthesis. Antibiotics treatment eliminated the beneficial effects of KGMs on gut flora, SCFAs, GPCRs and bile acid synthesis. By contrast, fecal microbiota transplantation (FMT) treatment restored the structure of intestinal microbiota. And after FMT treatment, KGM-M displayed higher hypoglycemic activity than KGM-L, probably due to the better effects on intestinal microbiota, SCFAs production, GPCRs expression and bile acid synthesis inhibition.
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Diabetes Mellitus , Microbioma Gastrointestinal , Ratos , Animais , Hipoglicemiantes/farmacologia , Peso Molecular , Ácidos Graxos Voláteis/metabolismo , Ácidos e Sais Biliares/farmacologiaRESUMO
INTRODUCTION: Aiming to kill bacteria in dentin tubules of infected dental pulp cavities, we evaluated the effects of sodium hypochlorite (NaOCl) solution agitated by different irrigation protocols, i.e., conventional needle irrigation (CNI), passive ultrasonic irrigation (PUI), the EDDY tip, and the neodymium-doped yttrium aluminum perovskite (Nd:YAP) laser. The EDDY achieved good antibacterial effects as passive ultrasonic irrigation in the coronal and middle thirds. Nd:YAP laser irradiation and PUI were effective in the apical third of the root canal. OBJECTIVES: To evaluate the ability of NaOCl agitated by high-frequency sonic irrigation-EDDY, PUI, and Nd:YAP laser-to kill bacteria in infected root canal walls and if the associated temperature increases at the root surface during application. METHODOLOGY: Infected root canal models were established, and roots were randomly divided into six groups: negative control, positive control, CNI, PUI, sonic agitation with EDDY, and Nd:YAP laser groups. After irrigation, the teeth were split and stained using the LIVE/DEAD BacLight Bacterial Viability Kit. Dead bacteria depth was evaluated by a confocal laser scanning microscopy and the temperature at the root surface was assessed using a thermal imaging camera during the irrigation process. RESULTS: In the coronal and middle thirds of the root canal, PUI and EDDY had stronger antibacterial effects than CNI (p<0.05); in the apical third, the antibacterial effects of PUI and Nd:YAP laser-activated irrigation were better than CNI (p<0.05). The maximum change in temperature was significantly greater during continuous Nd:YAP laser application compared with the other methods, but intermittent irrigation helped lessening this trend. CONCLUSIONS: NaOCl agitated by EDDY tip and PUI exhibited a similar bacteria elimination effect in the coronal and middle root canal. Nd:YAP laser was effective in the apical third and intermittent irrigation reduced its thermal impact.
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Cavidade Pulpar , Ultrassom , Tratamento do Canal Radicular , Bactérias , AntibacterianosRESUMO
One of the most effective ways to solve the problem of knowledge graph completion is embedding-based models. Graph neural networks (GNNs) are popular and promising embedding models which can exploit and use the structural information of neighbors in knowledge graphs. The current GNN-based knowledge graph completion methods assume that all neighbors of a node have equal importance. This assumption which cannot assign different weights to neighbors is pointed out in our study to be unreasonable. In addition, since the knowledge graph is a kind of heterogeneous graph with multiple relations, multiple complex interactions between nodes and neighbors can bring challenges to the effective message passing of GNNs. We then design a multi-relational graph attention network (MRGAT) which can adapt to different cases of heterogeneous multi-relational connections and then calculate the importance of different neighboring nodes through a self-attention layer. The incorporation of self-attention mechanism into the network with different node weights optimizes the network structure, and therefore, significantly results in a promotion of performance. We experimentally validate the rationality of our models on multiple benchmark knowledge graphs, where MRGAT achieves the best performance on various evaluation metrics including MRR score, Hits@ score compared with other state-of-the-art baseline models.
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Algoritmos , Reconhecimento Automatizado de Padrão , Conhecimento , Bases de Conhecimento , Redes Neurais de ComputaçãoRESUMO
The mechanism of Da-KGM showed poorer hypolipidemic effect, has not elucidated in previous study. Here, we performed hyperlipidemic hamsters administrated with 6% KGM (Konjac Glucomannan) and Da-KGM respectively to evaluate different underlying mechanisms. Poorer lipid-lowering effect was shown with Da-KGM treatment, and marked changes in relative abundance of Aldercreutzia and Parasutterella were not detected as KGM. Meanwhile, significant alteration of Ileibacterium was observed between KGM and Da-KGM group. Moreover, pathway of primary bile acids synthesis was enriched in cecal metabolites. KGM, not Da-KGM, remarkably increased concentration of Glycocholic acid (GCA) and Ursodeoxycholic acid (UDCA), which were negatively corrected with Ileibacterium. Marked increases in ileal Farnesoid X receptor (FXR) and hepatic Cholesterol 7α-hydroxylase (CYP7A1) were observed in KGM group, along with strong reduction of ileal Multi-drug resistance-associated protein2 (MRP2/ABCC2) and hepatic FXR expression, but not in Da-KGM group. There were no obvious changes in serum lipid level and bile acids, as well as gene expression after antibiotic treatment. Our results revealed that different hypolipidemic effects of KGM and Da-KGM might be associated with gut microbiota and bile acids metabolism.