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Untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a widely used method for discovering natural products (NPs); however, automatic MS/MS data mining for the discovery of NPs remains a challenge. In this work, LindenaneExtractor, a program based on characteristic MS/MS ions of lindenane sesquiterpenoids (LSs) was developed to automatically extract the LSs features for target LS discovery in plant extracts. To build this program, fragmentation mechanisms of characteristic ions of LSs were elucidated and confirmed by quantum chemical calculation and deuterium-labeled compounds. Subsequently, the information of characteristic ions was integrated and coded to develop LindenaneExtractor, which was further examined by standards and several public databases. Finally, the target LS features in Sarcandra hainanensis extract were automatically extracted by LindenaneExtractor and visualized by feature-based molecular networking and two-dimensional (2D) retention time-m/z plot, leading to the discovery of 96 target LSs in total, 37 of these compounds were potentially new NPs and one was confirmed by further isolation. This work proposed a new strategy for target NP analysis and discovery based on automatic MS/MS data mining, which could significantly improve the efficiency and accuracy of NP discovery.
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Produtos Biológicos , Sesquiterpenos , Produtos Biológicos/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Mineração de Dados , Humanos , Íons , Extratos Vegetais , Espectrometria de Massas em Tandem/métodosRESUMO
Three novel lindenane-monoterpene heterodimers with different skeleton types (1-3), together with a known analogue (4), were obtained from the seeds of Sarcandra glabra. Their structures were elucidated on the basis of comprehensive spectroscopic analyses, single crystal X-ray diffraction, and calculations of ECD. Sarcaglarone A (1) displayed an unprecedented monocyclic monoterpene moiety formed by a free-radical-mediated C1'-C5' bond formation reaction. 6α-Hydroxysarglaperoxide A (2) and 7'-oxyisosarcaglabrin A (3) are C23 and C25 terpenes formed by [2 + 2 + 2] cycloaddition and the Diels-Alder reaction, respectively. Their inhibitory activities against nitric oxide (NO) production were evaluated.
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Monoterpenos , Sementes , Terpenos , Óxido Nítrico/análise , Estrutura MolecularRESUMO
Brominated flame retardants (BFRs) are a series of stable and outstanding flame retardants bringing human exposure risks in indoor environment. However, sampling methods now available for BFRs are solvent-consuming and relatively complicated. This study provides a new option of low-volume air sampling device using cartridges with a sorbent mixture for different types of legacy and novel BFRs. In this study, we found that HC-C18 sorbent is most suitable for polybrominated diphenyl ethers (PBDEs) and novel BFRs (NBFRs) enrichment, and that NH2 for hexabromocyclododecanes (HBCDs). The sorbent mixture was optimized using a complex of HC-C18 and NH2 sorbents with elution recovery of 69.4% ± 7.9-117% ± 10%, pumping-through recovery of 84.5% ± 7.9-127% ± 36%, and breakthrough recovery of 70.8% ± 3.4-118% ± 6% for PBDEs, NBFRs, and HBCDs in indoor air. A sequential elution was also achieved using hexane for PBDEs and NBFRs and ethyl acetate for HBCDs. The method was validated with field sampling at nine student dormitory rooms. For legacy BFRs, all the isomers of HBCDs were detected in the air of nine rooms with the median concentrations of 91, 33, and 25 pg/m3 for (±)α-HBCD, (±)ß-HBCD, (±)γ-HBCD, respectively, while PBDEs were hardly detected. In contrast, NBFRs were detected at total concentrations of 15-811 pg/m3. Pentabromotoluene (PBT) was the most frequently detected NBFRs with a median concentration of 4 pg/m3, followed by EHTBB at 56 pg/m3 and HBBZ at 21 pg/m3. For the risk assessment, the total hazard index value for air inhalation of BFRs was estimated at 6.1â10-4-0.35, which are consistently lower than 1, indicating no immediate health risk, while their long-term effects remain worth concerns.
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Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental/métodos , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Hidrocarbonetos Bromados/análise , Adolescente , Adsorção , Adulto , Habitação , Humanos , Medição de Risco , Adulto JovemRESUMO
Modern retrieval systems tend to deteriorate because of their large output of useless and even misleading information, especially for complex search requests on a large scale. Complex information retrieval (IR) tasks requiring multi-hop reasoning need to fuse multiple scattered text across two or more documents. However, there are two challenges for multi-hop retrieval. To be specific, the first challenge is that since some important supporting facts have little lexical or semantic relationship with the retrieval query, the retriever often omits them; the second challenge is that once a retriever chooses misinformation related to the query as the entities of cognitive graphs, the retriever will fail. In this study, in order to improve the performance of retrievers in complex tasks, an intelligent sensor technique was proposed based on a sub-scope with cognitive reasoning (2SCR-IR), a novel method of retrieving reasoning paths over the cognitive graph to provide users with verified multi-hop reasoning chains. Inspired by the users' process of step-by-step searching online, 2SCR-IR includes a dynamic fusion layer that starts from the entities mentioned in the given query, explores the cognitive graph dynamically built from the query and contexts, gradually finds relevant supporting entities mentioned in the given documents, and verifies the rationality of the retrieval facts. Our experimental results show that 2SCR-IR achieves competitive results on the HotpotQA full wiki and distractor settings, and outperforms the previous state-of-the-art methods by a more than two points absolute gain on the full wiki setting.
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Swietenia is a genus in the plant family Meliaceae. This genus contains seven to eight known species, found in the tropical and subtropical regions of the Americas and West Africa. Thus far, more than 160 limonoids have been isolated from four species of the genus Swietenia. Limonoids are rich in structure type and biological activity, and these compounds are the main active components in the Swietenia species. This paper will give a comprehensive overview of the recent phytochemical and pharmacological research on the terpenes from Swietenia plants and encourage further drug discovery research.
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Limoninas/química , Limoninas/farmacologia , Meliaceae/química , Estrutura Molecular , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Relação Estrutura-AtividadeRESUMO
The self-assembly process of formation of worm-like micelles of a block copolymer-platinum(ii) complex hybrid is investigated with respect to the influence of solvent quality. When the solvent quality is moderately weakened, unilamellar free-standing sheets are achieved, in which the worm-like micelles snap off to form star micelles together with a few short worms. Extremely worsened solvent quality leads to unilamellar vesicle-like nanostructures, onto which only star micelles emerged. With the intermediate solvent quality, the sheets coexist with the vesicle-like nanostructures. This is well correlated with mechanistic insights regarding the morphological transition from sheet- to vesicle-like nanoassemblies. In these aggregates, short worms and star micelles still hold their core-shell structures. Furthermore, these unconventional superstructures are well interrelated with their luminescence properties. This result challenges the conventional paradigm of the amphiphilic self-assembly of surfactants and block copolymers in selective solvents, where they form bilayered nanostructures and are required universally to be rearranged during the morphological transition from micelles to vesicles.
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Biomimetic robots yearn for compliant actuators that are comparable to biological muscle in both functions and structural properties. For that, electrostatic actuators have been developed to imitate bio-muscle in features of fast response, high power, energy-efficiency, etc. However, those actuators typically lack impact damping performance, making them vulnerable and unstable in real applications. Here, we present auxetic electrostatic actuators that address this issue and demonstrate muscle-like performance by using elastomer-enhanced auxetics and electrostatic zipping mechanism. The proposed actuators contract linearly on applied voltage, producing large actuation strength (15 N) and contraction ratio (59%). Fabricated from readily available materials, our prototypes can quickly attenuate vibrations caused by impacts and absorb shock energy in 0.3 s. Furthermore, leveraging their 2-dimensional working mode and self-locking mechanism, a stiffness-changing muscle for a robotic arm and an active tensegrity device exemplify the potential applications of auxetic electrostatic actuators to a wide range of bionic robots.
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NLRP3 inflammasome plays an important role in autoimmunity and the dysregulation of NLRP3 inflammasome can lead to various human diseases. Natural products are an important source for the discovery of safe and effective inflammatory inhibitors. Chloranthalactone B (CTB), a lindenane sesquiterpenoid (LS) from a common traditional Chinese medicine (TCM) (Sarcandra glabra), could significantly inhibit the level of IL-1ß. This study aims to investigate the anti-inflammatory mechanism and target of CTB and its therapeutic effects on inflammatory diseases. CTB significantly inhibited IL-1ß secretion induced by different agonists. Co-IP and flow cytometry results showed that CTB inhibited NLRP3-NEK7 interactions, but had no significant effect on upstream events. Pull-down, DARTS, CETSA, biolayer interferometry assay (BLI), and LC/MS/MS results showed that CTB could covalently bind to cysteine 279 (Cys279) in the NACHT domain of NLRP3. The result of the chemical modification indicated that the epoxide motif was the key group of CTB for its anti-inflammatory effect of CTB. Further animal studies showed that CTB significantly reduced the symptoms and inflammation levels of gout, peritonitis, and acute lung injury. However, the protective effect of CTB against peritonitis and gout was abolished in NLRP3-knocked out (NLRP3 KO) mice. Overall, our research revealed that CTB was a specific NLRP3 covalent inhibitor, and epoxide motif was an active pharmacophore that covalently binds to NLRP3, which provided new insights in designing new NLRP3 inhibitors for treating NLRP3-driven diseases.
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Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Humanos , Masculino , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Células HEK293 , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lactonas/farmacologia , Lactonas/química , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Sesquiterpenos/farmacologia , Sesquiterpenos/químicaRESUMO
Estimating shipping nitrogen oxides (NOx) emissions and their associated ambient NO2 impacts is a complex and time-consuming task. In this study, a satellite-based ship pollution estimation model (SAT-SHIP) is developed to estimate regional shipping NOx emissions and their contribution to ambient NO2 concentrations in China. Unlike the traditional bottom-up approach, SAT-SHIP employs satellite observations with varying wind patterns to improve the top-down emission inversion methods for individual sectors amidst irregular emission plume signals. Through SAT-SHIP, shipping NOx emissions for 17 ports in China are estimated. The results show that SAT-SHIP performed comparably with the bottom-up approach, with an R2 value of 0.8. Additionally, SAT-SHIP reveals that the shipping sector in port areas contributes â¼21 and 11% to NO2 concentrations in the Yangtze River Delta and Pearl River Delta areas of China, respectively, which is consistent with the results from chemical transportation model simulations. This approach has practical implications for policymakers seeking to identify pollution sources and develop effective strategies to mitigate air pollution.
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BACKGROUND: Duck Tembusu virus is a member of the Ntaya group in the genus Flavivirus. The virus has been responsible for severe duck egg-drop syndrome in China since 2010. Its emergence and rapid spread have caused great economic loss for the poultry industry. The epidemiology of the virus infection and the potential threat to public health is of great concern because of the infective and zoonotic nature of flaviviruses. RESULTS: In this study, the pathogenicity of duck Tembusu virus in BALB/c mice was investigated. Infected mice developed clinical signs, including loss of appetite, ruffled hair, weight loss, disorientation, blindness and paralysis of hind limbs from six days post- infection following intracerebral inoculation. Morbidity was 100%, with mortality ranging from 20 to 80% in three- to eight-week-old mice. High virus titers were recovered from the brain, and the virus was distributed in several organs. Histologically, there was widespread non-suppurative encephalitis in the brain. Lymphocyte depletion in the spleen was observed, along with fatty degeneration in the liver and kidney. CONCLUSIONS: Our results demonstrate, for the first time, that duck Tembusu virus is highly neurovirulent in BALB/c mice. The mouse model used in this work was able to produce Tembusu virus infection and could be useful for elucidating some of the aspects of the pathophysiology of other flavivirus infections.
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Encefalite Viral/patologia , Encefalite Viral/virologia , Infecções por Flavivirus/patologia , Infecções por Flavivirus/virologia , Flavivirus/patogenicidade , Estruturas Animais/patologia , Estruturas Animais/virologia , Animais , China , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Análise de SobrevidaRESUMO
Two new sesquiterpenoids, sarglanoids G and H (1 and 2), together with two known analogues (3-4) were isolated from the roots of Sarcandra glabra. Compound 2 was a rare elemene-type sesquiterpenoid with a furan ring fragment, which is mostly lactone ring in its analogues. The structures of new compounds were determined on the basis of extensive spectroscopic methods including HR-ESI-MS, 1D and 2D NMR, and the absolute configuration of 1 was established by ECD calculations. Their anti-inflammatory activities were also evaluated.
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With the decreasing regional-transported levels, the health risk assessment derived from fine particulate matter (PM2.5) has become insufficient to reflect the contribution of local source heterogeneity to the exposure differences. Here, we combined the both ultra-high-resolution PM2.5 concentration with population distribution to provide the personal daily PM2.5 internal dose considering the indoor/outdoor exposure difference. A 30-m PM2.5 assimilating method was developed fusing multiple auxiliary predictors, achieving higher accuracy (R2 = 0.78-0.82) than the chemical transport model outputs without any post-simulation data-oriented enhancement (R2 = 0.31-0.64). Weekly difference was identified from hourly mobile signaling data in 30-m resolution population distribution. The population-weighted ambient PM2.5 concentrations range among districts but fail to reflect exposure differences. Derived from the indoor/outdoor ratio, the average indoor PM2.5 concentration was 26.5 µg/m3. The internal dose based on the assimilated indoor/outdoor PM2.5 concentration shows high exposure diversity among sub-groups, and the attributed mortality increased by 24.0% than the coarser unassimilated model.
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Duck egg-drop syndrome virus (DEDSV) is a newly emerging pathogenic flavivirus causing avian diseases in China. The infection occurs in laying ducks characterized by a severe drop in egg production with a fatality rate of 5-15â%. The virus was found to be most closely related to Tembusu virus (TMUV), an isolate from mosquitoes in South-east Asia. Here, we have sequenced and characterized the full-length genomes of seven DEDSV strains, including the 5'- and 3'-non-coding regions (NCRs). We also report for the first time the ORF sequences of TMUV and Sitiawan virus (STWV), another closely related flavivirus isolated from diseased chickens. We analysed the phylogenetic and antigenic relationships of DEDSV in relation to the Asian viruses TMUV and STWV, and other representative flaviviruses. Our results confirm the close relationship between DEDSV and TMUV/STWV and we discuss their probable evolutionary origins. We have also characterized the cleavage sites, potential glycosylation sites and unique motifs/modules of these viruses. Additionally, conserved sequences in both 5'- and 3'-NCRs were identified and the predicted secondary structures of the terminal sequences were studied. Antigenic cross-reactivity comparisons of DEDSV with related pathogenic flaviviruses identified a surprisingly close relationship with dengue virus (DENV) and raised the question of whether or not DEDSV may have a potential infectious threat to man. Importantly, DEDSV can be efficiently recognized by a broadly cross-reactive flavivirus mAb, 2A10G6, derived against DENV. The significance of these studies is discussed in the context of the emergence, evolution, epidemiology, antigenicity and pathogenicity of the newly emergent DEDSV.
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Antígenos/imunologia , Infecções por Flavivirus/veterinária , Flavivirus/genética , Flavivirus/imunologia , Genoma Viral , Doenças das Aves Domésticas/virologia , Sequência de Aminoácidos , Animais , Antígenos/genética , Sequência de Bases , Linhagem Celular , China , Reações Cruzadas , Cisteína/genética , Vírus da Dengue/genética , Vírus da Dengue/imunologia , Patos/imunologia , Patos/virologia , Infecções por Flavivirus/virologia , Glicosilação , Dados de Sequência Molecular , Fases de Leitura Aberta , Filogenia , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/imunologia , Análise de Sequência de DNARESUMO
It has been shown in previous studies that the autonomic nervous system can be affected by acupuncture. Within this study, teleacupuncture between China and Austria is used for quantifying the effects of heart rate (HR) and heart rate variability (HRV) in 33 Chinese patients (27 females, 6 males; mean age ± SD 49.5 ± 13.1 years; range 22-72 years) suffering from depression. Electrocardiographic signals before, during, and after acupuncture at the acupoint Baihui (GV20) were recorded in Harbin and analyzed in Graz using teleacupuncture. HRV data were analyzed in the time and frequency domain. Mean HR decreased significantly (P < 0.05) during and after acupuncture, whereas total HRV increased significantly after the third acupuncture stimulation period (P < 0.05) and also 5-10 minutes after (P < 0.05) acupuncture. The study shows that HRV could be a useful parameter for quantifying clinical effects of acupuncture on the autonomic nervous system.
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OBJECTIVES: Zirconia is an important dental implant material, yet it surfaces milling method is still under investigation. To explore the feasibility of laser etching in processing fine micro grooves on the surface of zirconia and to observe fine micro groove structure' influence on mouse embryonic osteoblasts, the survey was conducted. METHODS: 31 zirconia discs were made and polished to mirror surface. Then, they were divided into 3 groups: the mirror group, the femtosecond laser ablated microgroove group and the air blasted + acid etched group. Then, the surface properties of zirconia discs were analyzed by Scanning Electron Microscope/Energy Dispersive Spectrometer (SEM/EDS), X-Ray Diffraction (XRD), Atomic Force Microscope (AFM), water contact angle test and micro-Vickers hardness test. The biocompatibility of each machined zirconia was tested by cell proliferation test and SEM analyze of cell morphology. Then, the effect of these surface treatment to MC-3T3-E1's osteogenic differentiation was evaluated by Q-PCR test. RESULTS: SEM image showed that the femtosecond laser is a reliable method for forming regular-arranged microgrooves with pitch width of around 5 µm. EDS and XRD indicated that there were stable and purified tetragonal crystal system on the laser-roughened surface. AFM suggested that laser machining generated rougher surface (Ra) (271.7 ± 67.2 nm) than other groups. Furthermore, the contact angle showed laser ablated grooves induced anisotropic wetting. The micro-Vickers hardness test ascertained that laser-ablation strengthened zirconia surface. In vitro experiment showed that MC-3T3-E1 grown along the long axis of microgrooves on the first day. Besides, Real time PCR implied that osteogenesis-related gene expression OPN and ALP was much higher than the rest groups. SIGNIFICANCE: Femtosecond laser is able to machine zirconia with ultra-fine microgrooves (around 2.5 µm). These structures promoted MC-3T3-E1 cell to line along the microstructure and differentiate into osteogenic cells. Thus, femtosecond laser might be a potential processing options for zirconia micro-texturing.
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Osteogênese , Zircônio , Animais , Materiais Dentários , Lasers , Teste de Materiais , Camundongos , Microscopia Eletrônica de Varredura , Propriedades de Superfície , Zircônio/químicaRESUMO
Sarglanoids A-F, six new sesquiterpenoids belonging to eudesmane (1-5) and eremophilane (6) types, were isolated from the leaves of Sarcandra glabra, a famous traditional Chinese medicine (TCM). Their structures including absolute configurations were elucidated through extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Compounds 1-2 were rare N-containing eudesmane-type sesquiterpenoids. Compound 3 exhibited inhibitory activity against nitric oxide (NO) production in lipopolysaccharides (LPS)-induced RAW 264.7 cells with IC50 values at 20.00 ± 1.30 µmol·L-1. These findings provide scientific evidence for sesquiterpenoids as the material foundation of S. glabra.
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Sesquiterpenos , Estrutura Molecular , Folhas de Planta , Sesquiterpenos Policíclicos , Sementes , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Sarglaoxolane A (1), the first lindenane-normonoterpene heterodimer fused by tetrahydrofuran, was discovered in Sarcandra glabra guided by the first proposed single-node-based molecular networking approach. Moreover, two pseudonatural derivatives (2 and 3) with an oxa-difuranofurone moiety were transformed from 1 and confirmed by X-ray diffraction, and also proven to exist in the plant extract. A combination of molecular networking and biomimetic transformation can significantly promote the discovery and structural elucidation of novel natural products.
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Magnoliopsida , Magnoliopsida/química , Sementes , Extratos VegetaisRESUMO
The growing of vehicle population aggravates air pollution and threatens human health. In this study, based on the refined whole-process vehicle emission inventory considering volatile organic compounds (VOCs) evaporation emission, the CAMx model was applied to comprehensively quantify the impacts of the vehicle sector on the annual and seasonal concentrations of PM2.5 and O3 in China. Also, the health risks caused by long-term exposure to PM2.5 and O3 were evaluated. The model results showed that vehicle emission was an important source of severe O3 pollution in summer, with a contribution of more than 30% in most parts of China, but not an important source of serious PM2.5 pollution in winter, with a contribution of less than 20% in heavily polluted regions in China. Compared to tailpipe emission, vehicle VOCs evaporation emission led to increases of 25% and 47% to sectoral contribution to PM2.5 and O3. Health risk assessment results showed that attributable deaths caused by long-term exposure to PM2.5 and O3 were 975,029 and 46,043 in 2018, to which vehicle emission contributed approximately 12.5% and 22.2%, respectively.
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Poluentes Atmosféricos , Poluição do Ar , Ozônio , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Monitoramento Ambiental , Humanos , Material Particulado/análise , Emissões de Veículos/análiseRESUMO
A various amount of alveolar ridge resorption is likely to occur after tooth extraction, making it difficult to restore the missing teeth with either endosseous dental implants or prosthodontics approaches. It is commonly thought that the bone resorption is due to the absence of the mechanical stimulation from the occlusal force. However, regulation of the bone mass is a complex homeostatic system involved in hormonal, paracrine/autocrine, mechanical and neuronal nature. Studies have shown that the central and peripheral nervous system play an important role in bone remodeling. The hypothalamus integrates peripheral and central signals, and sends efferent hormonal and neuronal signals in response to stimulation. Numerous neuropeptides detected in the bone marrow have effect on the osteoblast and osteoclast. After tooth extraction, great loss of the axons is observed in the edentulous bone. So we speculate that innervation in the alveolar bone regulates the bone resorption in edentulous area. Methods to promote the nerve regeneration are expected to prevent the jaw bone resorption. The hypothesis also implies that after the placement of the oral implant the abundant nerves in the alveolar bone can increase the bone healing ability and long term survival rate of the implant.
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Reabsorção Óssea/prevenção & controle , Arcada Osseodentária/inervação , Arcada Osseodentária/fisiologia , Nervos Periféricos/fisiologia , Extração Dentária , Humanos , Nervos Periféricos/patologiaRESUMO
Marginal bone loss during bone healing exists around non-submerged dental implants. The aim of this study was to identify the relationship between different degrees of marginal bone loss during bone healing and the salivary microbiome. One hundred patients were recruited, and marginal bone loss around their implants was measured using cone beam computed tomography during a 3-month healing period. The patients were divided into three groups according to the severity of marginal bone loss. Saliva samples were collected from all subjected and were analysed using 16S MiSeq sequencing. Although the overall structure of the microbial community was not dramatically altered, the relative abundance of several taxonomic groups noticeably changed. The abundance of species in the phyla Spirochaeta and Synergistetes increased significantly as the bone loss became more severe. Species within the genus Treponema also exhibited increased abundance, whereas Veillonella, Haemophilus and Leptotrichia exhibited reduced abundances, in groups with more bone loss. Porphyromonasgingivalis, Treponemadenticola and Streptococcus intermedius were significantly more abundant in the moderate group and/or severe group. The severity of marginal bone loss around the non-submerged implant was associated with dissimilar taxonomic compositions. An increased severity of marginal bone loss was related to increased proportions of periodontal pathogenic species. These data suggest a potential role of microbes in the progression of marginal bone loss during bone healing.