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The formation of cell polarity is essential for many developmental processes such as polar cell growth and spatial patterning of cell division. A plant-specific ROP (Rho-like GTPases from Plants) subfamily of conserved Rho GTPase plays a crucial role in the regulation of cell polarity. However, the functional study of ROPs in angiosperm is challenging because of their functional redundancy. The Marchantia polymorpha genome encodes a single ROP gene, MpROP, providing an excellent genetic system to study ROP-dependent signaling pathways. Mprop knockout mutants exhibited rhizoid growth defects, and MpROP was localized at the tip of elongating rhizoids, establishing a role for MpROP in the control of polar cell growth and its functional conservation in plants. Furthermore, the Mprop knockout mutant showed defects in the formation of meristem notches associated with disorganized cell division patterns. These results reveal a critical function of MpROP in the regulation of plant development. Interestingly, these phenotypes were complemented not only by MpROP but also Arabidopsis AtROP2, supporting the conservation of ROP's function among land plants. Our results demonstrate a great potential for M. polymorpha as a powerful genetic system for functional and mechanistic elucidation of ROP signaling pathways during plant development.
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Proteínas de Arabidopsis , Arabidopsis , Marchantia , Meristema/genética , Meristema/metabolismo , Arabidopsis/metabolismo , Marchantia/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , División Celular/genética , Plantas/metabolismoRESUMEN
Confocal fluorescence imaging of fine structures of the cell membrane is important for understanding their biofunctions but is often neglected due to the lack of an effective method. Herein, we develop new amphiphilic rhodamine fluorescent probe RMGs in combination with basal imaging for this purpose. The probes show high signal-to-noise ratio and brightness and low internalization rate, making them suitable for imaging the fine substructures of the cell membrane. Using the representative probe RMG3, we not only observed the cell pseudopodia and intercellular nanotubes but also monitored the formation of migrasomes in real time. More importantly, in-depth imaging studies on more cell lines revealed for the first time that hepatocellular carcinoma cells secreted much more adherent extracellular vesicles than other cell lines, which might serve as a potential indicator of liver cells. We believe that RMGs may be useful for investigating the fine structures of the cell membrane.
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Membrana Celular , Colorantes Fluorescentes , Rodaminas , Colorantes Fluorescentes/química , Rodaminas/química , Humanos , Membrana Celular/química , Imagen Óptica , Microscopía Confocal/métodos , Tensoactivos/químicaRESUMEN
N6 -methyladenosine (m6 A) modification has been identified as one of the most important epigenetic regulation mechanisms in the development of human cancers. However, the association between m6 A-associated single-nucleotide polymorphisms (m6 A-SNPs) and lung cancer risk remains largely unknown. Here, we identified m6 A-SNPs and examined the association of these m6 A-SNPs with lung cancer risk in 13,793 lung cancer cases and 14,027 controls. In silico functional annotation was used to identify causal m6 A-SNPs and target genes. Furthermore, methylated RNA immunoprecipitation and quantitative real-time polymerase chain reaction (MeRIP-qPCR) assay was performed to assess the m6 A modification level of different genotypes of the causal SNP. In vitro assays were performed to validate the potential role of the target gene in lung cancer. A total of 8794 m6 A-SNPs were detected, among which 397 SNPs in nine susceptibility loci were associated with lung cancer risk, including six novel loci. Bioinformatics analyses indicated that rs1321328 in 6q21 was located around the m6 A modification site of AK9 and significantly reduced AK9 expression (ß = -0.15, p = 2.78 × 10-8 ). Moreover, AK9 was significantly downregulated in lung cancer tissues than that in adjacent normal tissues of samples from the Cancer Genome Atlas and Nanjing Lung Cancer Cohort. MeRIP-qPCR assay suggested that C allele of rs1321328 could significantly decrease the m6 A modification level of AK9 compared with G allele. In vitro assays verified the tumor-suppressing role of AK9 in lung cancer. These findings shed light on the pathogenic mechanism of lung cancer susceptibility loci linked with m6 A modification.
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Adenina , Neoplasias Pulmonares , Polimorfismo de Nucleótido Simple , Humanos , Adenina/análogos & derivados , Epigénesis Genética , Genes Supresores de Tumor , Neoplasias Pulmonares/genética , Adenilato Quinasa/metabolismoRESUMEN
Evidence regarding the link between long-term ambient ozone (O3) exposure and childhood sleep disorders is little. This study aims to examine the associations between long-term exposure to O3 and sleep disorders in children. We conducted a population-based cross-sectional survey, including 185,428 children aged 6-18 years in 173 schools across 14 Chinese cities during 2012 and 2018. Parents or guardians completed a checklist using Sleep Disturbance Scale for Children, and O3 exposure at residential and school addresses was estimated using a satellite-based spatiotemporal model. We used generalized linear mixed models to test the associations with adjustment for factors including socio-demographic variables, lifestyle, meteorology and multiple pollutants. Mean concentrations of O3, particulate matter with diameters ≤2.5 mm (PM2.5) and nitrogen dioxide (NO2) were 89.0 µg/m3, 42.5 µg/m3 and 34.4 µg/m3, respectively. O3 and NO2 concentrations were similar among provinces, while PM2.5 concentration varied significantly among provinces. Overall, 19.4% of children had at least one sleep disorder. Long-term exposure to O3 was positively associated with odds of sleep disorders for all subtypes. For example, each interquartile increment in home-school O3 concentrations was associated with a higher odds ratio for global sleep disorder, at 1.22 (95% confidence interval: 1.18, 1.26). Similar associations were observed for sleep disorder subtypes. The associations remained similar after adjustment for PM2.5 and NO2. Moreover, these associations were heterogeneous regionally, with more prominent associations among children residing in southeast region than in northeast and northwest regions in China. We concluded that long-term exposure to O3 is positively associated with risks of childhood sleep disorders. These associations varied by geographical region of China.
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Information on the spatio-temporal patterns of the burden of ischemic heart disease (IHD) caused by ambient ambient fine particulate matter (PM2.5) in the global level is needed to prioritize the control of ambient air pollution and prevent the burden of IHD. The Global Burden of Disease Study (GBD) 2019 provides data on IHD attributable to ambient PM2.5. The IHD burden and mortality attributable to ambient PM2.5 were analyzed by year, age, gender, socio-demographic index (SDI) level, geographical region and country. Estimated annual percentage change (EAPC) was calculated to estimate the temporal trends of age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) from 1990 to 2019. Globally, the ASMR and ASDR for ambient PM2.5-related IHD tended to level off generally, with EAPC of -0.03 (95% CI: -0.06, 0.12) and 0.3 (95% CI: 0.22, 0.37), respectively. In the past 30 years, there were obvious differences in the trend of burden change among different regions. A highest increased burden was estimated in low-middle SDI region (EAPC of ASMR: 3.73 [95% CI: 3.56, 3.9], EAPC of ASDR: 3.83 [95% CI: 3.64, 4.02]). In contrast, the burden in high SDI region (EAPC of ASMR: -4.48 [95% CI: -4.6, -4.35], EAPC of ASDR: -3.98 [95% CI: -4.12, -3.85]) has declined most significantly. Moreover, this burden was higher among men and older populations. EAPCs of the ASMR (R = -0.776, p < 0.001) and ASDR (R = -0.781, p < 0.001) of this burden had significant negative correlations with the countries' SDI level. In summary, although trends in the global burden of IHD attributable to ambient PM2.5 are stabilizing, but this burden has shifted from high SDI countries to middle and low SDI countries, especially among men and elderly populations. To reduce this burden, the air pollution management prevention need to be further strengthened, especially among males, older populations, and middle and low SDI countries.
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Contaminación del Aire , Isquemia Miocárdica , Anciano , Masculino , Humanos , Carga Global de Enfermedades , Contaminación del Aire/efectos adversos , Contaminación Ambiental , Isquemia Miocárdica/epidemiología , Años de Vida Ajustados por Calidad de Vida , Salud GlobalRESUMEN
BACKGROUND: Insulin resistance has been reported to increase the risk of breast, prostate and colorectal cancer. However, the role of insulin resistance and its interaction with genetic risk in the development of lung cancer remains controversial. Therefore, we aimed to explore the association between a novel metabolic score for insulin resistance (METS-IR) and lung cancer risk. METHODS: A total of 395 304 participants without previous cancer at baseline were included. The Cox proportional hazards regression model was performed to investigate the association between METS-IR and lung cancer risk. In addition, a Mendelian randomization analysis was also performed to explore the causal relationship. The joint effects and additive interactions between METS-IR and polygenetic risk score (PRS) of lung cancer were also investigated. RESULTS: During a median follow-up of 11.03 years (Inter-quartile range (IQR): 10.30-11.73), a total of 3161 incident lung cancer cases were diagnosed in 395 304 participants. There was a significant association between METS-IR and lung cancer risk, with an HR of 1.28 (95% CI: 1.17-1.41). Based on the Mendelian randomization analysis, however, no causal associations were observed. We observed a joint effect but no interaction between METS-IR and genetic risk. The lung cancer incidence was estimated to be 100.42 (95% CI: 91.45-109.38) per 100 000 person-year for participants with a high METS-IR and PRS, while only 42.76 (95% CI: 36.94-48.59) with low METS-IR and PRS. CONCLUSIONS: High METS-IR was significantly associated with an increased risk of lung cancer. Keeping a low level of METS-IR might help reduce the long-term incident risk of lung cancer.
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Resistencia a la Insulina , Neoplasias Pulmonares , Análisis de la Aleatorización Mendeliana , Humanos , Neoplasias Pulmonares/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Síndrome Metabólico/epidemiología , Adulto , Modelos de Riesgos Proporcionales , Anciano , IncidenciaRESUMEN
Recent evidence has pinpointed a key role of the microbiome in human respiratory health and disease. However, significant knowledge gaps still exist regarding the connection between bacterial communities and adverse effects caused by particulate matters (PMs). Here, we characterized the bacterial microbiome along different airway sites in occupational pneumoconiosis (OP) patients. The sequencing data revealed that OP patients exhibited distinct dysbiosis in the composition and function of the respiratory microbiota. To different extents, there was an overall increase in the colonization of microbiota, such as Streptococcus, implying a possible intrusion pathway provided by exogenous PMs. Compared to those of healthy subjects, unhealthy living habits (i.e., smoking) had a greater impact on microbiome changes in OP patients. Importantly, the associations between the bacterial community and disease indicators indicated that specific bacterial species, including Prevotella, Actinobacillus, and Leptotrichia, might be surrogate markers of OP disease progression. Collectively, our results highlighted the potential participation of the bacterial microbiota in the pathogenesis of respiratory diseases and helped in the discovery of microbiome-based diagnostics for PM-induced disorders.
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Mitochondrial fission is a highly regulated process that can affect metabolism, proliferation, and apoptosis. Division at the periphery enables damaged material to be shed into smaller mitochondria destined for mitophagy, which is found preceded by increased Ca2+ and reactive oxygen species, as well as reduced membrane potential and pH. However, the variation of hypochlorous acid (HOCl) during the peripheral fission has not been well studied, and the existing fluorescent probes are unsuitable for detecting mitochondrial HOCl because of the 0.8-fold decreased pH during this process. Herein, we design a novel CCS (changeable π-conjugation system)-based probe (ON-mito) with a dibenzo[1,4]oxazepine core, which can selectively react with HOCl at pH 6.4, generating an oxazine-containing product that emits at 660 nm. The capability of ON-mito for imaging the HOCl generation in HeLa cells during mitophagy is demonstrated under weakly acidic condition. Further, with ON-mito, we find for the first time a burst increase of the mitochondrial HOCl in COS-7 cells during peripheral fission, which may serve as an important indicator of this process. Probe ON-mito may be useful for studying mitochondrial damage under diverse conditions.
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Colorantes Fluorescentes , Ácido Hipocloroso , Humanos , Colorantes Fluorescentes/metabolismo , Ácido Hipocloroso/metabolismo , Células HeLa , Mitocondrias/metabolismo , Diagnóstico por ImagenRESUMEN
The neurotoxic effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on offspring animals are well-documented. However, epidemiological evidence for legacy PFAS is inconclusive, and for alternative PFAS, it is little known. In this investigation, we selected 718 mother-child pairs from the Chinese Maoming Birth Cohort Study and measured 17 legacy and alternative PFAS in the third-trimester serum. Neuropsychological developments (communication, gross motor function, fine motor function, problem solving ability, and personal-social skills) were assessed at 3, 6, 12, 18, 24, and 36 months using the Ages and Stages Questionnaires 3rd edition. Trajectories of each subscale were classified into persistently low and persistently high groups via group-based trajectory modeling. Logistic regression and grouped weighted quantile sum were fitted to assess the potential effects of individual PFAS and their mixtures, respectively. Higher linear PFHxS levels were associated with elevated odds for the persistently low trajectories of communication (OR = 1.73; 95% CI: 1.12, 2.66) and problem solving ability (OR = 2.11; 95% CI: 1.14, 3.90). Similar findings were observed for linear PFOS, 1m-PFOS, PFDA, PFDoDA, PFUnDA, and legacy PFAS mixture. However, no association was observed for alternative PFAS and their mixture. We provided insights into the longitudinal links between prenatal legacy/alternative PFAS exposure and neuropsychological development trajectories over the first 3 years of life.
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Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Efectos Tardíos de la Exposición Prenatal , Humanos , Embarazo , Femenino , Contaminantes Ambientales/toxicidad , Estudios de Cohortes , Fluorocarburos/toxicidad , Ácidos Alcanesulfónicos/toxicidadRESUMEN
The limited characterization and detection capacity of unknown compounds hinder our understanding of the molecular composition of toxic compounds in PM2.5. The present study applied Fourier transform ion cyclotron resonance mass spectrometry coupled with negative and positive electrospray ionization sources (ESI-/ESI+ FT-ICR-MS) to probe the molecular characteristics and dynamic formation processes of the effective proinflammatory components in organic aerosols (OAs) of PM2.5 in Guangzhou for one year. We detected abundant proinflammatory molecules in OAs, mainly classified as CHON compounds (compounds composed of C, H, O, and N atoms) in elemental and nitroaromatic compounds (NACs) in structures. From the perspective of the formation process, we discovered that these proinflammatory molecules, especially toxic NACs, were largely driven by secondary nitrate formation and biomass burning (in emission source), as well as SO2 (in atmospheric evolution). In addition, our results indicated that the secondary processes had replaced the primary emission as the main contributing source of the toxic proinflammatory compounds in OAs. This study highlights the importance of community measures to control the production of nitroaromatic compounds derived from secondary nitrate formation and biomass burning in urban areas.
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Nitratos , Compuestos Orgánicos , Nitratos/análisis , Biomasa , Espectrometría de Masas , Compuestos Orgánicos/análisis , Material Particulado/análisis , Aerosoles/análisis , BioensayoRESUMEN
We develop a general method to study ultrafast laser induced charge migration in molecules, which includes both electronic and nuclear dynamics. The method can be applied to relatively large systems. A detailed analysis of charge migration in pyrene is performed. Decoherences and recoherences of charge migration in pyrene are found and explained in terms of nuclear motions.
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As the main biomarkers of most diseases, enzymes play fundamental but extremely critical roles in biosystems. High-resolution studies of enzymes using activatable in situ fluorescence imaging may help to better elucidate their dynamics in living systems. Currently, most activatable probes can realize changeable imaging of enzymes but inevitably tend to diffuse away from the original active site of the enzyme and even translocate out of cells, seriously impairing in situ high-resolution observation of the enzymes. In situ fluorescence imaging of enzymes can be realized by labelling probes or antibodies with always-on signals that fail to enable activatable imaging of enzymes. Thus, fluorescent probes with both "activatable" and "in situ" properties will enable high-resolution studies of enzymes in living systems. In this tutorial review, we summarize the existing methods ranging from design strategies to bioimaging applications that could be used to develop activatable fluorescent probes for in situ imaging of enzymes. It is expected that this tutorial review will promote the new methods generated to design such probes for better deciphering enzymes in complex biosystems and further extend the application of these methods to other fields of enzymes.
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Colorantes Fluorescentes , Imagen Óptica , BiomarcadoresRESUMEN
Identifying key drivers of manufacturing CO2 emissions is critical to carbon reduction practices. For manufacturing, CO2 emissions are mainly determined by production capacity and production scale. However, traditional production-theoretical decomposition analysis (PDA) fails to consider production-scale-related drivers. To better support policy development and implementation, this paper improves PDA based on industrial linkage theory. The improved model can identify seven production-capacity-related drivers and five production-scale-related drivers, allowing a comprehensive understanding of CO2 emission drivers. Then this model is implemented to investigate CO2 emission changes in 18 manufacturing sectors in Hubei Province, China, from 2012 to 2017. Results show that manufacturing CO2 reduction efforts in Hubei Province have yielded some achievements, with reduced potential energy intensity and improved CO2 emission technical efficiency in most sectors. Changes in external market demand and final demand structure have contributed to CO2 reduction in most sectors. Results also reveal some problems in manufacturing in Hubei Province, such as the inability to improve CO2 emission technical efficiency and CO2 emission technology strength, the slow improvement of energy utilization technical efficiency and energy utilization technology strength, and the reduction of value-added rate.
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Dióxido de Carbono , Industrias , Dióxido de Carbono/análisis , Comercio , Carbono/análisis , Tecnología , China , Desarrollo EconómicoRESUMEN
INTRODUCTION: The objective of this study was to explore the effect of augmented corticotomy (AC) on anterior alveolar bone morphology in presurgical orthodontic treatment for skeletal Class III malocclusion. METHODS: Thirty-six surgical patients with skeletal Class III malocclusion with high-angle were included: 18 (AC group) accepted AC surgery during presurgical orthodontic treatment, and 18 (control group) accepted traditional presurgical orthodontic treatment. Cone-beam computed tomography scans were obtained before treatment (T0) and after presurgical orthodontic treatment (T1). The alveolar bone morphology, root length, dehiscence, and movement of mandibular central incisors were measured by cone-beam computed tomography using Dolphin software. Statistical analyses were performed with independent-sample t tests, paired t tests, and multiple linear regression. RESULTS: After presurgical orthodontic treatment, the whole alveolar bone thickness at each level, alveolar bone area, and alveolar bone height decreased significantly in the control group but increased or remained unchanged in the AC group. In the AC group, the lower the labial alveolar bone height at T0 was, the greater the increase after T1; the change in alveolar bone thickness was related to ΔL1-MP and sex. At T0, the incidences of dehiscence were similar in the 2 groups, ranging from 11.11% to 16.67%. At T1, the labial and lingual incidences of dehiscence in the AC group were 0% and 27.78%, compared with 55.56% and 66.67% in the control group. CONCLUSIONS: During presurgical orthodontic treatment, AC is effective in preventing alveolar bone resorption and dehiscence without additional root resorption. AC can be recommended for high-angle skeletal Class III patients with thin alveolar bone around anterior teeth during presurgical orthodontic treatment.
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Pérdida de Hueso Alveolar , Maloclusión de Angle Clase III , Humanos , Pérdida de Hueso Alveolar/prevención & control , Huesos , Cefalometría/métodos , Tomografía Computarizada de Haz Cónico , Incisivo , Maloclusión de Angle Clase III/cirugía , Mandíbula/cirugíaRESUMEN
BACKGROUND: Accurate identification of protein complexes in protein-protein interaction (PPI) networks is crucial for understanding the principles of cellular organization. Most computational methods ignore the fact that proteins in a protein complex have a functional similarity and are co-localized and co-expressed at the same place and time, respectively. Meanwhile, the parameters of the current methods are specified by users, so these methods cannot effectively deal with different input PPI networks. RESULT: To address these issues, this study proposes a new method called MP-AHSA to detect protein complexes with Multiple Properties (MP), and an Adaptation Harmony Search Algorithm is developed to optimize the parameters of the MP algorithm. First, a weighted PPI network is constructed using functional annotations, and multiple biological properties and the Markov cluster algorithm (MCL) are used to mine protein complex cores. Then, a fitness function is defined, and a protein complex forming strategy is designed to detect attachment proteins and form protein complexes. Next, a protein complex filtering strategy is formulated to filter out the protein complexes. Finally, an adaptation harmony search algorithm is developed to determine the MP algorithm's parameters automatically. CONCLUSIONS: Experimental results show that the proposed MP-AHSA method outperforms 14 state-of-the-art methods for identifying protein complexes. Also, the functional enrichment analyses reveal that the protein complexes identified by the MP-AHSA algorithm have significant biological relevance.
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Algoritmos , Mapeo de Interacción de Proteínas , Biología Computacional/métodos , Mapeo de Interacción de Proteínas/métodos , Mapas de Interacción de Proteínas , Proteínas/metabolismoRESUMEN
Nitric oxide (NO) is a crucial neurotransmitter participating in many biological processes via nitrosylation reaction. NO produced in diverse subcellular regions also regulates the function of cells in different manners. A Golgi apparatus is rich in nitric oxide synthase and may serve as a potential therapeutic target for Alzheimer's disease (AD). However, due to the lack of an effective tool, it is difficult to reveal the relationship between Golgi-NO and AD. Herein, we report Golgi-NO as the first Golgi-targeted fluorescent probe for sensing and imaging NO in the Golgi apparatus. The probe is designed and synthesized by incorporating 4-sulfamoylphenylamide as a Golgi-targeted moiety to 6-carboxyrhodamine B, generating a fluorophore of Golgi-RhB with modifiable carboxyl, which is then combined with the NO recognition moiety of o-diaminobenzene. The probe shows superior analytical performance including accurate Golgi-targeted ability and high selectivity for NO. Moreover, using the probe, we disclose a significant increase of NO in Golgi apparatus in the AD model. This study provides a competent tool for studying the function and nitrosylation of NO in the Golgi apparatus in related diseases.
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Enfermedad de Alzheimer , Óxido Nítrico , Enfermedad de Alzheimer/diagnóstico por imagen , Colorantes Fluorescentes , Aparato de Golgi , HumanosRESUMEN
Airborne nano-scale particulate matter (nPM) exposure is a risk factor for neurological diseases. However, to date, there has been no comprehensive evaluation of ambient nPM's neurotoxicity. We examined the toxic effects of nPM on human neurons derived from induced pluripotent stem cells (iPSCs) at doses ranging from 0 to 200 µg/mL, and employed whole-genome RNA-sequencing in different dose groups to gain further insight into the neurotoxicity of ambient nPM. Our findings showed that nPM was absorbed by neurons, and induced a variety of toxic effects. The apical benchmark dose lower confidence bound (aBMDL) values of each effect endpoint were ranked as follows, in ascending order: mitochondrial membrane potential, neurite length, early apoptosis, cell viability. BMD analysis based on transcriptomic data revealed that the point of departure (PoD) of the 20 pathways with the lowest p-values (0.75 µg/mL), the top 20 upstream regulators (0.79 µg/mL) and the neurological diseases (0.77 µg/mL) could be appropriate for nPM neurotoxicity evaluation. The transcriptomic PoDs (tPoDs) were similar to apical PoDs (aPoDs) since their absolute fold differences were within 10-fold. Further analysis of the transcriptomic data revealed that nPM exposure could disturb the pathways related to ferroptosis, neurotransmitters, xenobiotic metabolism, etc., which might be critical in regulating nPM neurotoxicity. We also found that low-dose nPM induced cytokine signaling pathways, while high doses of nPM activated cell-cycle regulation and DNA repair pathways. Our results indicate that BMD modeling based on transcriptomic data could be useful in illustrating the neurotoxic mechanism, and also could be a promising method for evaluating the potential health risks of nPM.
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Células Madre Pluripotentes Inducidas , Síndromes de Neurotoxicidad , Benchmarking , Humanos , Neuronas , Síndromes de Neurotoxicidad/genética , Material Particulado/toxicidad , TranscriptomaRESUMEN
Cigarette smoke (CS), a complex chemical indoor air pollutant, induces degradation of elastin, resulting in emphysema. Aberrant cross-talk between macrophages and bronchial epithelial cells is essential for the degradation of elastin that contributes to emphysema, in which extracellular vesicles (EVs) play a critical role. The formation of N6-methyladenosine (m6A) is a modification in miRNA processing, but its role in the development of emphysema remains unclear. Here, we established that production of excess mature microRNA-93 (miR-93) in bronchial epithelial cells via enhanced m6A modification was mediated by overexpressed methyltransferase-like 3 (METTL3) induced by CS. Mature miR-93 was transferred from bronchial epithelial cells into macrophages by EVs. In macrophages, miR-93 activated the JNK pathway by targeting dual-specificity phosphatase 2 (DUSP2), which elevated the levels of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 12 (MMP12) and induced elastin degradation, leading to emphysema. These results demonstrate that METTL3-mediated formation of EV miR-93, facilitated by m6A, is implicated in the aberrant cross-talk of epithelium-macrophages, indicating that this process is involved in the smoking-related emphysema. EV miR-93 may use as a novel risk biomarker for CS-induced emphysema.
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Enfisema , Vesículas Extracelulares , MicroARNs , Elastina , Epitelio/metabolismo , Humanos , Macrófagos/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Fumar/efectos adversosRESUMEN
AIM: To establish a fast, sensitive and accurate high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for determining the monosaccharide content of Qingzhuan Dark Tea polysaccharides in different years (2 years, 5 years and 11 years). METHODS: The optimised chromatographic conditions were achieved on a C18 column (5.0 µm, 250 mm × 4.6 mm inner diameter). The mobile phase flow rate was 0.9 mL/min and the column temperature was set to 27°C. The aqueous phase A (5 mM aqueous ammonium acetate) and organic phase B (acetonitrile) were used to elute the target analyses isocratically (0-60 min: 18% B). The mass spectrometer detector was equipped with an electron spray ionisation (ESI)source, and multiple reaction monitoring (MRM) mode was used for the determination of 1-phenyl-3-methyl-5-pyrazolone (PMP) derived monosaccharides. RESULTS: We carried out a comprehensive methodological validation of PMP derived monosaccharides, including linearity, precision, stability and repeatability. Nine monosaccharides (rhamnose, mannose, ribose, glucose, galacturonic acid, xylose, galactose, fucose and arabinose) of Qingzhuan Dark Tea polysaccharides were identified, in which ribose and fucose were reported for the first time. The results showed the contents of these nine monosaccharides differed significantly among different years. CONCLUSIONS: The validated method is reliable, accurate, repeatable and can be applied to quality assessment of these monosaccharides.
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Monosacáridos , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida , Fucosa , Monosacáridos/análisis , Monosacáridos/química , Polisacáridos/análisis , Polisacáridos/química , Ribosa , TéRESUMEN
INTRODUCTION: This study aimed to quantify the periodontal health of incisors during surgical orthodontic treatment in patients with high-angle Class III malocclusion using a cone-beam computed tomography (CBCT) 3-dimensional (3D) reconstruction technique. METHODS: The sample consisted of 30 patients with high-angle Class III malocclusion (mean age, 20.53 ± 2.86 years). CBCT images were taken before treatment (T0), after presurgical orthodontic treatment, and after treatment (T2). In addition, 3D tooth and alveolar bone models were generated. The root surface area, periodontal ligament (PDL)_Area, and vertical bone level (VBL) around the maxillary and mandibular central incisors were measured. RESULTS: The root surface area and PDL_Area of maxillary and mandibular central incisors decreased continuously between T0 and T2 (P <0.01). At T2, mandibular central incisors showed 38.64 ± 13.39% PDL_Area loss, and maxillary central incisors exhibited 21.13 ± 16.48% PDL_Area loss. For mandibular central incisors, the PDL_Area loss caused by VBL loss was significantly greater than that for maxillary central incisors (P <0.01) and significantly greater than the PDL_Area loss caused by root resorption (P <0.01). From T0 to T2, the lingual surface of maxillary central incisors exhibited greater VBL loss than the other 3 surfaces (P <0.01), and the labial and lingual surfaces of mandibular central incisors demonstrated greater VBL loss than proximal surfaces (P <0.01). CONCLUSIONS: The 3D CBCT reconstruction method provides useful information regarding the periodontal defects of incisors in patients with high-angle skeletal Class III malocclusion. The PDL_Area of maxillary and mandibular central incisors decreased continuously during the treatment. Vertical alveolar bone levels at proximal surfaces appeared to be relatively stable.