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Photoactive artificial nanocatalysts that mimic natural photoenergy systems can yield clean and renewable energy. However, their poor photoabsorption capability and disfavored photogenic electron-hole recombination hinder their production. Herein, we designed two nanocatalysts with various microstructures by combining the tailored self-assembly of the meso-tetra(p-hydroxyphenyl) porphine photosensitizer with the growth of titanium dioxide (TiO2). The porphyrin photoabsorption antenna efficiently extended the absorption range of TiO2 in the visible region, while anatase TiO2 promoted the efficient electron-hole separation of porphyrin. The photo-induced electrons were transferred to the surface of the Pt co-catalyst for the generation of hydrogen via water splitting, and the hole was utilized for the decomposition of methyl orange dye. The hybrid structure showed greatly increased photocatalytic performance compared to the core@shell structure due to massive active sites and increased photo-generated electron output. This controlled assembly regulation provides a new approach for the fabrication of advanced, structure-dependent photocatalysts.
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Under the long-term pressure overload stimulation, the heart experiences embryonic gene activation, leading to myocardial hypertrophy and ventricular remodelling, which can ultimately result in the development of heart failure. Identifying effective therapeutic targets is crucial for the prevention and treatment of myocardial hypertrophy. Histone lysine lactylation (HKla) is a novel post-translational modification that connects cellular metabolism with epigenetic regulation. However, the specific role of HKla in pathological cardiac hypertrophy remains unclear. Our study aims to investigate whether HKla modification plays a pathogenic role in the development of cardiac hypertrophy. The results demonstrate significant expression of HKla in cardiomyocytes derived from an animal model of cardiac hypertrophy induced by transverse aortic constriction surgery, and in neonatal mouse cardiomyocytes stimulated by Ang II. Furthermore, research indicates that HKla is influenced by glucose metabolism and lactate generation, exhibiting significant phenotypic variability in response to various environmental stimuli. In vitro experiments reveal that exogenous lactate and glucose can upregulate the expression of HKla and promote cardiac hypertrophy. Conversely, inhibition of lactate production using glycolysis inhibitor (2-DG), LDH inhibitor (oxamate) and LDHA inhibitor (GNE-140) reduces HKla levels and inhibits the development of cardiac hypertrophy. Collectively, these findings establish a pivotal role for H3K18la in pathological cardiac hypertrophy, offering a novel target for the treatment of this condition.
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Cardiomegalia , Histonas , Ácido Láctico , Miócitos Cardíacos , Animais , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Histonas/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Miócitos Cardíacos/efeitos dos fármacos , Camundongos , Ácido Láctico/metabolismo , Processamento de Proteína Pós-Traducional , Modelos Animais de Doenças , Glucose/metabolismo , Masculino , Lisina/metabolismo , Camundongos Endogâmicos C57BL , GlicóliseRESUMO
Early adolescence is a critical period for the development of children's intelligence mindsets, which play a significant role in academic achievement. However, existing research predominantly employs variable-centered approaches, which fail to capture individual differences in mindset-achievement relations. This research addresses this gap by adopting a longitudinal person-centered approach to explore the joint developmental trajectories of growth and fixed mindsets among early adolescents. It further explores how these trajectories relate to changes in academic achievement (i.e., the mean of standardized mathematics and Chinese achievement test scores) over 2 years, accounting for intelligence and sociodemographic factors such as age, sex, and family SES. In two five-wave longitudinal studies with 748 (Mage = 10.23 years, SD = 0.30; 49% girls at T1) and 3258 (Mage = 10.34 years, SD = 0.37; 49% girls at T1) Chinese elementary school students from grades 4 to 6, four distinct mindset trajectory profiles were identified: Growth (initially high growth but low fixed mindsets), Fixed (initially high fixed but low growth mindsets), Moderate (initially moderate levels in both mindsets), and Both-High (initially high levels in both mindsets). Analysis across both studies revealed that students in the Growth trajectory profile exhibited the most significant improvements in academic achievement 2 years later. Conversely, students in the Both-High trajectory profile experienced the least favorable academic outcomes. These findings highlight the importance of recognizing individual differences in mindset trajectories and their potential impact on academic outcomes. The current research underscores the need for educational interventions that are tailored to different mindset profiles to optimize student development and achievement.
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Noise, as an unavoidable stress (pressure) source in the modern life, affects animals in many ways, both behaviorally and physiologically. Behavioral changes may be driven by changes in hormone secretion in animals. When animals face with noise stress, the neuroendocrine systems, mainly the hypothalamic-pituitary-adrenal (HPA) axis, are activated, which promotes the secretion and release of stress hormones, and then leads to a series of behavioral changes. The behavioral changes can be easily observed, but the changes in physiological indicators such as hormone levels need to be accurately measured. Currently, many studies have measured the variations of stress hormone levels in animals under different noise conditions. Taking glucocorticoid as an example, this paper summarizes the different measurement methods of stress hormones, especially the non-invasive measurement methods, and compares the advantages and shortcomings of them. It provides a variety of measurement choices for the study of related issues, and also helps us to further understand the sources of animal stress, in order to provide a better habitat for animals.
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Sistema Hipotálamo-Hipofisário , Ruído , Sistema Hipófise-Suprarrenal , Estresse Fisiológico , Animais , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Estresse Fisiológico/fisiologia , Glucocorticoides/metabolismo , Estresse Psicológico/fisiopatologiaRESUMO
Interest in socioeconomic differences in academic motivation has been longstanding. However, previous research has often treated both low- and high-SES students as homogenous groups. This study aims to address this gap by investigating the developmental trajectory profiles of mathematics motivation during early adolescence, with a focus on variations within and across SES groups. Multigroup latent class growth analysis was used on a sample of 3718 early adolescents in China (initial Mage was 9.40 ± 0.52 years; 48.0% girls) across 2 years from grades 4 through 6. The analysis identified three distinct self-determined mathematics motivation trajectory profiles within each SES group: a good-quality profile (i.e., initially high autonomous but low controlled), a high-quantity profile (i.e., initially high both autonomous and controlled), and a low-quantity profile (i.e., initially low both autonomous and controlled). A greater proportion of low-SES students were observed within the low-quantity profile than within the good-quality profile. The study found that the failure-is-enhancing view was a protective factor against two relatively maladaptive motivational trajectory profiles (i.e., high-quantity profile and low-quantity profile), irrespective of socioeconomic background. These findings emphasize the importance of implementing motivational interventions for early adolescents that consider both structural factors (e.g., socioeconomic backgrounds) and psychological factors (e.g., failure beliefs), to foster students' academic development.
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Matemática , Motivação , Classe Social , Humanos , Feminino , Masculino , China , Adolescente , Criança , Estudantes/psicologia , Sucesso AcadêmicoRESUMO
Bacterial resistance and excessive inflammation are common issues that hinder wound healing. Antimicrobial peptides (AMPs) offer a promising and versatile antibacterial option compared to traditional antibiotics, with additional anti-inflammatory properties. However, the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation. TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs. Therefore, in this study, a composite hydrogel (HAMA/t-GL13K) was prepared via the photocross-linking method, in which tFNAs carry GL13K. The hydrogel was injectable, biocompatible, and could be instantly photocured. It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS. Thereby, the hydrogel inhibited bacterial infection, shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring. The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.
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Infecções Bacterianas , Ácidos Nucleicos , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Ácidos Nucleicos/farmacologia , Hidrogéis/farmacologia , Hidrogéis/química , Cicatrização , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologiaRESUMO
Among the numerous complications of diabetes mellitus, diabetic wounds seriously affect patients' quality of life and result in considerable psychological distress. Promoting blood vessel regeneration in wounds is a crucial step in wound healing. Lonicerin (LCR), a bioactive compound found in plants of the Lonicera japonica species and other honeysuckle plants, exhibits anti-inflammatory and antioxidant activities, and it recently has been found to alleviate ulcerative colitis by enhancing autophagy. In this study we investigated the efficacy of LCR in treatment of diabetic wounds and the underlying mechanisms. By comparing the single-cell transcriptomic data from healing and non-healing states in diabetic foot ulcers (DFU) of 5 patients, we found that autophagy and SIRT signaling activation played a crucial role in mitigating inflammation and oxidative stress, and promoting cell survival in wound healing processes. In TBHP-treated human umbilical vein endothelial cells (HUVECs), we showed that LCR alleviated cell apoptosis, and enhanced the cell viability, migration and angiogenesis. Furthermore, we demonstrated that LCR treatment dose-dependently promoted autophagy in TBHP-treated HUVECs by upregulating Sirt1 expression, and exerted its anti-apoptotic effect through the Sirt1-autophagy axis. Knockdown of Sirt1 significantly decreased the level of autophagy, and mitigated the anti-apoptotic effect of LCR. In a STZ-induced diabetic rat model, administration of LCR significantly promoted wound healing, which was significantly attenuated by Sirt1 knockdown. This study highlights the potential of LCR as a therapeutic agent for the treatment of diabetic wounds and provides insights into the molecular mechanisms underlying its effects.
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Diabetes Mellitus Experimental , Luteolina , Cicatrização , Animais , Humanos , Ratos , Autofagia/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Luteolina/farmacologia , Luteolina/uso terapêutico , Qualidade de Vida , Sirtuína 1/genética , Sirtuína 1/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
Pulmonary arterial hypertension (PAH) is a severe disease resulting from progressive increases in pulmonary vascular resistance and pulmonary vascular remodeling, ultimately leading to right ventricular failure and even death. Hypoxia, inflammation, immune reactions, and epigenetic modifications all play significant contributory roles in the mechanism of PAH. Increasingly, epigenetic changes and their modifying factors involved in reprogramming through regulation of methylation or the immune microenvironment have been identified. Among them, histone lactylation is a new post-translational modification (PTM), which provides a novel visual angle on the functional mechanism of lactate and provides a promising diagnosis and treatment method for PAH. This review detailed introduces the function of lactate as an important molecule in PAH, and the effects of lactylation on N6-methyladenosine (m6A) and immune cells. It provides a new perspective to further explore the development of lactate regulation of pulmonary hypertension through histone lactylation modification.
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Introduction: Cyanogenic glycosides (CNglcs) are bioactive plant products involving in plant defense against herbivores by virtue of their abilities to release toxic hydrogen cyanide (HCN). Aspergillus niger has been shown to be effective in producing ß-glucosidase, which could degrade CNglcs. However, whether A. niger could remove CNglcs under ensiling conditions is still unknown. Methods: In this study, we first investigated the HCN contents in ratooning sorghums for two years, then the sorghums were ensiled with or without the addition of A. niger. Results: Two years' investigation indicated that the contents of HCN in fresh ratooning sorghum were larger than 801 mg/kg FW (fresh weight), which could not be reduced by silage fermentation under safety threshold (200 mg/kg FW). A. niger could produce ß-glucosidase over a range of pH and temperature, which degraded the CNglcs and removed the hydrogen cyanide (HCN) at early days of ratooning sorghum fermentation. The addition of A. niger (2.56 × 107 CFU/ml) altered the microbial community, increased bacterial diversity, improved the nutritive qualities, and reduced the HCN contents in ensiled ratooning sorghum lower than 100 mg/kg FW after 60 days of fermentation. Overall, the addition of 150 ml A. niger + 50 ml sterile water per 3 kg silage could efficiently remove CNglcs from ratooning sorghum silage. Conclusion: In conclusion, A. niger could produce ß-glucosidase which degraded the CNglcs during the early days of fermentation, benefiting the ensiling process and improving the utilization of ratooning sorghum.
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The Ras GTPase-activating protein SYNGAP1 plays a central role in synaptic plasticity, and de novo SYNGAP1 mutations are among the most frequent causes of autism and intellectual disability. How SYNGAP1 is regulated during development and how to treat SYNGAP1-associated haploinsufficiency remain challenging questions. Here, we characterize an alternative 3' splice site (A3SS) of SYNGAP1 that induces nonsense-mediated mRNA decay (A3SS-NMD) in mouse and human neural development. We demonstrate that PTBP1/2 directly bind to and promote SYNGAP1 A3SS inclusion. Genetic deletion of the Syngap1 A3SS in mice upregulates Syngap1 protein and alleviates the long-term potentiation and membrane excitability deficits caused by a Syngap1 knockout allele. We further report a splice-switching oligonucleotide (SSO) that converts SYNGAP1 unproductive isoform to the functional form in human iPSC-derived neurons. This study describes the regulation and function of SYNGAP1 A3SS-NMD, the genetic rescue of heterozygous Syngap1 knockout mice, and the development of an SSO to potentially alleviate SYNGAP1-associated haploinsufficiency.
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Processamento Alternativo , Deficiência Intelectual , Humanos , Camundongos , Animais , Regulação para Cima , Processamento Alternativo/genética , Neurônios/metabolismo , Camundongos Knockout , Deficiência Intelectual/genética , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genéticaRESUMO
Background: This study aimed to identify prognostic signatures to predict the prognosis of breast cancer (BRCA) patients based on a series of comprehensive analyses of gene expression data. Methods: The RNA-sequencing expression data and corresponding BRCA patient clinical data were collected from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. Firstly, the differently expressed genes (DEGs) related to prognosis between tumor tissues and normal tissues were ascertained by performing R package "limma". Secondly, the DEGs were used to construct a polygenic risk scoring model by the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator Cox regression (Lasso-cox) analysis method. Thirdly, survival analysis was performed to investigate the risk score values in the TCGA cohort. And the enrichment analysis, immune cell infiltration levels analysis, and protein-protein internet (PPI) analysis were performed. Simultaneously, the GEO cohort was used to validate the model. Lastly, we constructed a nomogram to explore the influence of polygenic risk score and other clinical factors on the survival probability of patients with BRCA. Results: A total of 1000 DEGs including 396 upregulated genes and 604 downregulated genes were identified from the TCGA-BRCA dataset. We obtained 5 prognosis-related genes, as the key biomarkers by Lasso-cox analysis (FBXL19, HAGHL, PHKG2, PKMYT1, and TXNDC17), all of which were significantly upregulated in breast tumors. The prognostic prediction of the 5 genes model was great in training and validation cohorts. Moreover, the high-risk group had a poorer prognosis. The Cox regression analysis showed that the comprehensive risk score for 5 genes was an independent prognosis factor. Conclusion: The 5 genes risk model constructed in this study had an independent predictive ability to distinguish patients with a high risk of death from those with a low-risk score, and it can be used as a practical and reliable prognostic tool for BRCA.
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Annually increasing electric vehicles will undoubtedly end in tremendous amount of waste LiFePO4 (LFP) batteries. In this work, a highly-efficient and easy-going solid-phase method is proposed for direct regeneration of the waste LFP cathode material (W-LFP). The W-LFP is successfully regenerated via heat treatment with the addition of Li2CO3, CNTs and glucose. After activation, the dispersibility of CNTs in water is improved, making it easier to mix well with other materials. Also, the hydroxyl and carboxyl groups on CNTs have a certain degree of reducibility, which is conducive to the reduction of Fe3+ to Fe2+. After subsequent heat treatment, the three-dimensional conductive network composed of CNTs greatly enhances the conductivity and the ionic diffusion coefficient of LFP, thereby improving its electrochemical performance. Meanwhile, the decay and regeneration mechanisms of LFP are investigated by characterization and electrochemical testing. The regenerated LFP achieves an excellent specific capacity of 155.47 mAh/g at 0.05 C, which is around 99% that of new LFP. Additionally, the costs of main consumption in the regeneration process only account for 33.7% the price of new LFP. This low-cost, high-value-added and solid-phase direct regeneration process is proved to have great economic and energy-saving potential, which is promising for recycling the waste LFP cathode materials.
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Fontes de Energia Elétrica , Lítio , Lítio/química , Eletrodos , Reciclagem , Íons/química , ResíduosRESUMO
As a typical type of persistent organic pollutant, perfluorooctanoic acid (PFOA) is pervasive in the environment. Multiple studies have found that PFOA has hepatotoxicity, but the mechanism remains poorly understood. In this study, the toxic effects of different concentrations of PFOA on zebrafish liver cells were systematically assessed by recording cell survival, ultrastructural observations, and transcriptome analyses. The results showed that the inhibition of cell viability and the massive accumulation of autophagic vacuoles were observed at 400 µM PFOA, while transcriptomic changes occurred with treatments of 1 and 400 µM PFOA. The transcription levels of 1055 (977 up- and 78 down-regulated genes) and 520 (446 up- and 74 down-regulated genes) genes were significantly changed after treatment with 1 and 400 µM PFOA, respectively. Based on Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, significant expression changes were observed in autophagy, tight junction, signal transduction, immune system, endocrine system, and metabolism-related pathways, indicating that such processes were greatly affected by PFOA exposure. The findings of this study will provide a scientific basis for the toxic effects and potential toxic mechanisms of PFOA on zebrafish, and provide information for ecological risk assessments.
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Poluentes Químicos da Água , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Poluentes Químicos da Água/toxicidade , Caprilatos/toxicidade , Caprilatos/metabolismo , FígadoRESUMO
Synapses are the basic units for information processing and storage in the nervous system. It is only when the synaptic connection is established, that it becomes meaningful to discuss the structure and function of a circuit. In humans, our unparalleled cognitive abilities are correlated with an increase in the number of synapses. Additionally, genes involved in synaptogenesis are also frequently associated with neurological or psychiatric disorders, suggesting a relationship between synaptogenesis and brain physiology and pathology. Thus, understanding the molecular mechanisms of synaptogenesis is the key to the mystery of circuit assembly and neural computation. Furthermore, it would provide therapeutic insights for the treatment of neurological and psychiatric disorders. Multiple molecular events must be precisely coordinated to generate a synapse. To understand the molecular mechanisms underlying synaptogenesis, we need to know the molecular components of synapses, how these molecular components are held together, and how the molecular networks are refined in response to neural activity to generate new synapses. Thanks to the intensive investigations in this field, our understanding of the process of synaptogenesis has progressed significantly. Here, we will review the molecular mechanisms of synaptogenesis by going over the studies on the identification of molecular components in synapses and their functions in synaptogenesis, how cell adhesion molecules connect these synaptic molecules together, and how neural activity mobilizes these molecules to generate new synapses. Finally, we will summarize the human-specific regulatory mechanisms in synaptogenesis and results from human genetics studies on synaptogenesis and brain disorders.
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The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several that exist only in a subset of species as well as substantial species-specific molecular differences across homologous neuronal, glial, and non-neural subtypes. The latter are exemplified by human-specific switching between expression of the neuropeptide somatostatin and tyrosine hydroxylase, the rate-limiting enzyme in dopamine production in certain interneurons. The above molecular differences are also illustrated by expression of the neuropsychiatric risk gene FOXP2, which is human-specific in microglia and primate-specific in layer 4 granular neurons. We generated a comprehensive survey of the dlPFC cellular repertoire and its shared and divergent features in anthropoid primates.
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Córtex Pré-Frontal Dorsolateral , Evolução Molecular , Primatas , Somatostatina , Tirosina 3-Mono-Oxigenase , Adulto , Animais , Dopamina/metabolismo , Córtex Pré-Frontal Dorsolateral/citologia , Córtex Pré-Frontal Dorsolateral/metabolismo , Humanos , Pan troglodytes , Primatas/genética , Análise de Célula Única , Somatostatina/genética , Somatostatina/metabolismo , Transcriptoma , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
High level noise can damage cochlear hair cells, auditory nerve and synaptic connections between cochlear hair cells and auditory nerve, resulting in noise-induced hearing loss (NIHL). Recent studies have shown that animal cochleae have circadian rhythm, which makes them different in sensitivity to noise throughout the day. Cochlear circadian rhythm has a certain relationship with brain-derived neurotrophic factor and glucocorticoids, which affects the degree of hearing loss after exposure to noise. In this review, we summarize the research progress of the regulation of cochlear sensitivity to noise by circadian rhythm and prospect the future research direction.
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Ritmo Circadiano , Perda Auditiva Provocada por Ruído , Animais , Limiar Auditivo , Cóclea , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Células Ciliadas Auditivas , Ruído/efeitos adversosRESUMO
Vitellogenin (Vg) is an important factor that impacts oocyte maturation, egg formation and embryonic development in Arthropoda. Two orthologs of Vg gene were obtained from the genome of Phytoseiulus persimilis and termed as PpVg1 and PpVg2. Both orthologs belong to the large lipid transfer protein superfamily. The expression of PpVg1 and PpVg2 was low in immatures and male adults, and increased rapidly in female adults after mating, and reached a peak before the first egg was laid (168× and 20.5× the level in virgin females, respectively). When PpVg1 and PpVg2 were interfered with dsRNA, the relative expression decreased by 81.0 and 30.9%, respectively, and 7.8 and 31.4% interfered individuals died within 24 h. Among surviving individuals, ca. 51.1 and 44.8% are infertile. Factors that might be related to expression of Vg genes are also discussed.
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Ácaros , Vitelogeninas , Animais , Feminino , Masculino , Reprodução , Vitelogeninas/genética , Vitelogeninas/metabolismoRESUMO
Fluoride-containing toothpaste is daily used in toothbrush. Some compounds derived from natural herbs that have antibacterial and anti-inflammatory activities has attracted increasing attention as potential supplements for the control of oral diseases. In this paper, a natural product mixture (NPM-8) containing eight herbs extracts was added to toothpaste, and its antibacterial and anti-inflammatory effects were investigated. The results showed that NPM-8-containing toothpaste exhibited superior and faster inhibitory and bactericidal effects against S. mutans, S. sanguinis and P. gingivalis than that of the NPM-8-free toothpaste. NPM-8-containing toothpaste significantly reduced the biomass of single-species or three-species biofilms. The cytotoxicity of the NPM-8-containing toothpaste was similar to that of the conventional fluoride toothpaste and CHX. The NPM-8-containing toothpaste could significantly inhibit IL-1ß and IL-6 production in HGE cells and exhibited a better anti-inflammatory effect than that of the NPM-8-free toothpaste. In conclusion, NPM-8-containing fluoride toothpaste is superior to conventional fluoride toothpaste in regard to their antibacterial, antibiofilm, and anti-inflammatory properties. NPM-8-containing toothpaste also has good biocompatibility and is safe for daily use. It indicates that NPM-8 is a promising natural product mixture in oral health.