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Targeted and enantioselective delivery of chiral diagnostic-probes and therapeutics into specific compartments inside cells is of utmost importance in the improvement of disease detection and treatment. The classical DNA 'light-switch' ruthenium(II)-polypyridyl complex, [Ru(DIP)2(dppz)]Cl2 (DIP = 4,7-diphenyl-1,10-phenanthroline, dppz = dipyridophenazine) has been shown to be accumulated only in the cytoplasm and membrane, but excluded from its intended nuclear DNA target. In this study, the cationic [Ru(DIP)2(dppz)]2+ is found to be redirected into live-cell nucleus in the presence of lipophilic 3,5-dichlorophenolate or flufenamate counter-anions via ion-pairing mechanism, while maintaining its original DNA recognition characteristics. Interestingly and unexpectedly, further studies show that only the Δ-enantiomer is selectively translocated into nucleus while the Λ-enantiomer remains trapped in cytoplasm, which is found to be mainly due to their differential enantioselective binding affinities with cytoplasmic proteins and nuclear DNA. More importantly, only the nucleus-relocalized Δ-enantiomer can induce obvious DNA damage and cell apoptosis upon prolonged visible-light irradiation. Thus, the use of Δ-enantiomer can significantly reduce the dosage needed for maximal treatment effect. This represents the first report of enantioselective targeting and photosensitization of classical Ru(II) complex via simple ion-pairing with suitable weak acid counter-anions, which opens new opportunities for more effective enantioselective cancer treatment.
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Núcleo Celular , Rutenio , Estereoisomerismo , Núcleo Celular/metabolismo , Luz , Aniones , ADN/metabolismoRESUMEN
Mitochondrial DNA (mtDNA) is known to play a critical role in cellular functions. However, the fluorescent probe enantio-selectively targeting live-cell mtDNA is rare. We recently found that the well-known DNA 'light-switch' [Ru(phen)2dppz]Cl2 can image nuclear DNA in live-cells with chlorophenolic counter-anions via forming lipophilic ion-pairing complex. Interestingly, after washing with fresh-medium, [Ru(phen)2dppz]Cl2 was found to re-localize from nucleus to mitochondria via ABC transporter proteins. Intriguingly, the two enantiomers of [Ru(phen)2dppz]Cl2 were found to bind enantio-selectively with mtDNA in live-cells not only by super-resolution optical microscopy techniques (SIM, STED), but also by biochemical methods (mitochondrial membrane staining with Tomo20-dronpa). Using [Ru(phen)2dppz]Cl2 as the new mtDNA probe, we further found that each mitochondrion containing 1-8 mtDNA molecules are distributed throughout the entire mitochondrial matrix, and there are more nucleoids near nucleus. More interestingly, we found enantio-selective apoptotic cell death was induced by the two enantiomers by prolonged visible light irradiation, and in-situ self-monitoring apoptosis process can be achieved by using the unique 'photo-triggered nuclear translocation' property of the Ru complex. This is the first report on enantio-selective targeting and super-resolution imaging of live-cell mtDNA by a chiral Ru complex via formation and dissociation of ion-pairing complex with suitable counter-anions.
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ADN Mitocondrial , Microscopía , Rutenio , Aniones , Luz , Mitocondrias , Rutenio/química , Microscopía/métodosRESUMEN
The long non-coding telomeric RNA transcript TERRA, in the form of an RNA-DNA duplex, regulates telomere recombination. In a screen for nucleases that affects telomere recombination, mutations in DNA2, EXO1, MRE11 and SAE2 cause severe delay in type II survivor formation, indicating that type II telomere recombination is mediated through a mechanism similar to repairing double-strand breaks. On the other hand, mutation in RAD27 results in early formation of type II recombination, suggesting that RAD27 acts as a negative regulator in telomere recombination. RAD27 encodes a flap endonuclease that plays a role in DNA metabolism, including replication, repair and recombination. We demonstrate that Rad27 suppresses the accumulation of the TERRA-associated R-loop and selectively cleaves TERRA of R-loop and double-flapped structures in vitro. Moreover, we show that Rad27 negatively regulates single-stranded C-rich telomeric DNA circles (C-circles) in telomerase-deficient cells, revealing a close correlation between R-loop and C-circles during telomere recombination. These results demonstrate that Rad27 participates in telomere recombination by cleaving TERRA in the context of an R-loop or flapped RNA-DNA duplex, providing mechanistic insight into how Rad27 maintains chromosome stability by restricting the accumulation of the R-loop structure within the genome.
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Endonucleasas de ADN Solapado , Estructuras R-Loop , Proteínas de Saccharomyces cerevisiae , ADN Helicasas/genética , ADN de Cadena Simple , Endonucleasas de ADN Solapado/genética , Endonucleasas de ADN Solapado/metabolismo , Recombinación Genética , ARN/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Telómero/genética , Telómero/metabolismoRESUMEN
The maturation of forebrain dopamine circuitry occurs over multiple developmental periods, extending from early postnatal life until adulthood, with the precise timing of maturation defined by the target region. We recently demonstrated in the adult mouse brain that axon terminals arising from midbrain dopamine neurons innervate the anterior corpus callosum and that oligodendrocyte lineage cells in this white matter tract express dopamine receptor transcripts. Whether corpus callosal dopamine circuitry undergoes maturational changes between early adolescence and adulthood is unknown but may be relevant to understanding the dramatic micro- and macro-anatomical changes that occur in the corpus callosum of multiple species during early adolescence, including in the degree of myelination. Using quantitative neuroanatomy, we show that dopamine innervation in the forceps minor, but not the rostral genu, of the corpus callosum, is greater during early adolescence (P21) compared to adulthood (>P90) in wild-type mice. We further demonstrate with RNAscope that, as in the adult, Drd1 and Drd2 transcripts are expressed at higher levels in oligodendrocyte precursor cells (OPCs) and decline as these cells differentiate into oligodendrocytes. In addition, the number of OPCs that express Drd1 transcripts during early adolescence is double the number of those expressing the transcript during early adulthood. These data further implicate dopamine in axon myelination and myelin regulation. Moreover, because developmental (activity-independent) myelination peaks during early adolescence, with experience-dependent (activity-dependent) myelination greatest during early adulthood, our data suggest that potential roles of dopamine on callosal myelination shift between early adolescence and adulthood, from a developmental role to an experience-dependent role.
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Cuerpo Calloso , Ratones Endogámicos C57BL , Receptores de Dopamina D1 , Receptores de Dopamina D2 , Animales , Ratones , Cuerpo Calloso/metabolismo , Cuerpo Calloso/crecimiento & desarrollo , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/genética , Masculino , Neuronas Dopaminérgicas/metabolismo , Dopamina/metabolismo , Células Precursoras de Oligodendrocitos/metabolismo , FemeninoRESUMEN
The uptake of plastic particles by plants and their transport through the food chain make great risks to biota and human health. Therefore, it is important to trace plastic particles in the plant. Traditional fluorescence imaging in plants usually suffers significant autofluorescence background. Here, we report a persistent luminescence nanoplatform for autofluorescence-free imaging and quantitation of submicrometer plastic particles in plant. The nanoplatform was fabricated by doping persistent luminescence nanoparticles (PLNPs) onto polystyrene (PS) nanoparticles. Cr3+-doped zinc gallate PLNP was employed as the dopant for autofluorescence-free imaging due to its persistent luminescence nature. In addition, the Ga element in PLNP was used as a proxy to quantify the PS in the plant by inductively coupled plasma mass spectrometry (ICP-MS). Thus, the developed nanoplatform allows not only dual-mode autofluorescence-free imaging (persistent luminescence and laser-ablation ICP-MS) but also ICP-MS quantitation for tracking PS in plant. Application of this nanoplatform in a typical plant model Arabidopsis thaliana revealed that PS mainly distributed in the root (>99.45%) and translocated very limited (<0.55%) to the shoot. The developed nanoplatform has great potential for quantitative tracing of submicrometer plastic particles to investigate the environmental process and impact of plastic particles.
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Arabidopsis , Nanopartículas , Arabidopsis/química , Nanopartículas/química , Luminiscencia , Plásticos/química , Tamaño de la Partícula , Poliestirenos/química , Imagen ÓpticaRESUMEN
Acrylamide (AAM), a compound extensively utilized in various industrial applications, has been reported to induce toxic effects across multiple tissues in living organisms. Despite its widespread use, the impact of AAM on ovarian function and the mechanisms underlying these effects remain poorly understood. Here, we established an AAM-exposed mouse toxicological model using 21 days of intragastric AAM administration. AAM exposure decreased ovarian coefficient and impaired follicle development. Further investigations revealed AAM would trigger apoptosis and disturb tricarboxylic acid cycle in ovarian tissue, thus affecting mitochondrial electron transport function. Moreover, AAM exposure decreased oocyte and embryo development potential, mechanically associated with pericentrin and phosphorylated Aurora A cluster failure, leading to meiotic spindle assembly defects. Collectively, these results suggest that AAM exposure may lead to apoptosis, glucose metabolic disorders, and mitochondrial dysfunction in ovary tissue, ultimately compromising oocyte quality.
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OBJECTIVE: To analyze the coupling and coordination level of medical education and health resource allocation in China, and to provide scientific basis for promoting the high-quality development of medical education and the efficient allocation of health resources. METHODS: Based on the panel data from 2011 to 2021, the coupling coordination degree model was used to measure the coupling coordination index of medical education and health resources in China. The spatial auto-correlation model was used to analyze the development status and distribution characteristics of the coupling coordination degree of the two systems. The kernel density estimation method was used to analyze the dynamic evolution trend of the coupling coordination of the two systems. The QR quantile regression model was used to explore the key factors affecting the coupling coordination degree of the two systems. RESULTS: During the observation period, the coupling coordination degree of the two systems increased from 0.393 to 0.465, with a growth rate of 18.3%. The coupling coordination degree between regions gradually decreased in the eastern-central and eastern-western regions, and there were still large differences between the central and western regions. The coupling coordination degree of the two systems in the region was significantly different in the eastern and western regions, and the central region was relatively similar. There is a positive spatial correlation between the provinces, and 25.81% of the provinces have transitions. Finally, the number of points in the first and third quadrants is higher than that in the second and fourth quadrants. In the process of dynamic distribution, the degree of polarization of the coupling coordination degree curve of the two systems is gradually weakened. Per capita GDP, residents ' income difference and population size are the positive and significant factors driving the coupling and coordinated development of the two systems. CONCLUSION: The coupling and coordination degree of the two systems of medical education and health resource allocation showed a stable upward trend during the observation period, and the global spatial positive correlation also gradually increased, showing the spatial agglomeration characteristics of ' high-high agglomeration ' and ' low-low agglomeration '. The spatial difference of coupling coordination degree shows a shrinking trend and develops towards equalization. The coupling coordination degree of the two systems is affected by social, economic and demographic factors to varying degrees. Therefore, it is necessary to innovate the coordinated development mechanism of the two systems, promote the two-way flow of medical education and health resource allocation in talents, technology and other elements, and then promote the coupling and coordinated development of the two systems.
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Educación Médica , Asignación de Recursos , China , Humanos , Asignación de Recursos para la Atención de Salud , Recursos en SaludRESUMEN
The SwissTargetPrediction was employed to predict the potential drug targets of the active component of Si-Miao-Yong-An decoction (SMYAD). The therapeutic targets for HF were searched in the Genecard database, and Cytoscape3.9.1 software was used to construct the "drug-component-target-disease network" diagram. In addition, the String platform was used to construct Protein-Protein Interaction (PPI) network, and the DAVID database was used for GO and KEGG analysis. AutoDockTools-1.5.6 software was used for molecular docking verification. Network pharmacology studies have shown that AKT 1, ALB, and CASP 3 are the key targets of action of SMYAD against heart failure. The active compounds are quercetin and kaempferol.
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BACKGROUND: Identification of the motifs bound by a transcription factor (TF) is important to reveal the function of TF. Previously, we built a transcription factor centered yeast one hybrid (TF-Centered Y1H) that could identify the motifs bound by a target TF. However, that method was difficult to comprehensively identify all the motifs bound by a TF. RESULTS: Here, we build an improved TF-Centered Y1H to comprehensively determine the motifs bound by a target TF. Recombination-mediated cloning in yeast was performed to construct a saturated prey library that contains 7 random base insertions. After TF-Centered Y1H screening, all the positive clones were pooled together to isolate pHIS2 vector. The insertion regions of pHIS2 were PCR amplified and the PCR product was subjected to high-throughput sequencing. The insertion sequences were then retrieved and analyzed using MEME program to identify the potential motifs bound by the TF. Using this technology, we studied the motifs bound by an ethylene-responsive factor (BpERF2) from birch. In total, 22 conserved motifs were identified, and most of them are novel cis-acting elements. Both the yeast one hybrid and electrophoretic mobility shift assay verified that the obtained motifs could be bound by BpERF2. In addition, chromatin immunoprecipitation (ChIP) study further suggested that the identified motifs can be bound by BpERF2 in cells of birch. These results together suggested that this technology is reliable and has biological significance. CONCLUSION: This method will have wide application in DNA-protein interaction studies.
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Saccharomyces cerevisiae , Factores de Transcripción , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Motivos de Nucleótidos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Técnicas del Sistema de Dos Híbridos , Regulación de la Expresión GénicaRESUMEN
BACKGROUND: Arbuscular mycorrhizal fungi (AMF) form symbiotic relationships with various terrestrial plants and have attracted considerable interest as biofertilizers for improving the quality and yield of medicinal plants. Despite the widespread distribution of AMFs in Salvia miltiorrhiza Bunge's roots, research on the impact of multiple AMFs on biomass and active ingredient accumulations has not been conducted. In this study, the effects of five native AMFs (Glomus formosanum, Septoglomus constrictum, Rhizophagus manihotis, Acaulospora laevis, and Ambispora gerdemannii) and twenty-six communities on the root biomass and active ingredient concentrations of S. miltiorrhiza were assessed using the total factor design method. RESULTS: Thirty-one treatment groups formed symbiotic relationships with S. miltiorrhiza based on the pot culture results, and the colonization rate ranged from 54.83% to 89.97%. AMF communities had higher colonization rates and total phenolic acid concentration than single AMF, and communities also appeared to have higher root fresh weight, dry weight, and total phenolic acid concentration than single inoculations. As AMF richness increased, there was a rising trend in root biomass and total tanshinone accumulations (ATTS), while total phenolic acid accumulations (ATP) showed a decreasing trend. This suggests that plant productivity was influenced by the AMF richness, with higher inoculation benefits observed when the communities contained three or four AMFs. Additionally, the affinities of AMF members were also connected to plant productivity. The inoculation effect of closely related AMFs within the same family, such as G. formosanum, S. constrictum, and R. manihotis, consistently yielded lower than that of mono-inoculation when any combinations were applied. The co-inoculation of S. miltiorrhiza with nearby or distant AMFs from two families, such as G. formosanum, R. manihotis, and Ac. laevis or Am. gerdemannii resulted in an increase of ATP and ATTS by more than 50%. AMF communities appear to be more beneficial to the yield of bioactive constituents than the single AMF, but overall community inoculation effects are related to the composition of AMFs and the relationship between members. CONCLUSION: This study reveals that the AMF community has great potential to improve the productivity and the accumulation of bioactive constituents in S. miltiorrhiza, indicating that it is an effective way to achieve sustainable agricultural development through using the AMF community.
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Micorrizas , Plantas Medicinales , Salvia miltiorrhiza , Humanos , Plantas Medicinales/microbiología , Raíces de Plantas , Hongos , Adenosina TrifosfatoRESUMEN
OBJECTIVES: The purpose of this study was to explore the value of red blood cell distribution width (RDW) and platelet-to-lymphocyte ratio (PLR) in predicting the occurrence of acute kidney injury (AKI) in critically ill patients. MATERIALS AND METHODS: Among 1,500 adult patients in the intensive care unit (ICU) between January 2016 and December 2019, we examined the associations of baseline RDW and PLR with the risk of AKI development using logistical analysis. In addition, we explored the value of RDW and PLR in predicting in-hospital mortality. RESULTS: Overall, 615 (41%) patients were diagnosed with AKI. We divided the groups into two subgroups each; the high-RDW (≥ 14.045%) group had a high risk of developing AKI (OR = 5.189, 95% CI: 4.088 - 6.588), and the high-PLR (≥ 172.067) group had a risk of developing AKI too (OR = 9.11, 95% CI: 7.09 - 11.71). The areas under the receiver operating characteristic curves (AUCs) for the prediction of AKI incidence based on RDW and PLR were 0.780 (95% CI: 0.755 - 0.804) and 0.728 (95% CI: 0.702 - 0.754) (all p < 0.001), with cut-off values of 14.045 and 172.067, respectively. Moreover, a higher RDW was associated with a higher rate of hospital mortality (OR: 2.907, 2.190 - 3.858), and the risk of in-hospital mortality related to PLR was 1.534 (95% CI: 1.179 - 1.995). CONCLUSION: A higher RDW was related to a higher risk of AKI occurrence and in-hospital mortality in the ICU.
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Lesión Renal Aguda , Enfermedad Crítica , Adulto , Humanos , Índices de Eritrocitos , Linfocitos , Curva ROC , Eritrocitos , Lesión Renal Aguda/epidemiología , Estudios Retrospectivos , PronósticoRESUMEN
Alzheimer's disease (AD) is a common age-related neurodegenerative disease that strikes millions worldwide. Herein, we demonstrate a new approach based on network target to identify anti-AD compounds from Danshen. Network pharmacology and molecular docking were employed to establish the DS-AD network, which mainly involved apoptosis of neuron cells. Then network scoring was confirmed via Connectivity Map analysis. M308 (Danshenxinkun D) was an anti-AD candidate with a high score (p < 0.01). Furthermore, we conducted ex vivo experiments with H2O2-treated PC12 cells to verify the neuroprotective effect of Salvia miltiorrhiza-containing plasma (SMP), and UPLC-Q-TOF/MS and RT-qPCR were performed to demonstrate the anti-AD activity of M308 from SMP. Results revealed that SMP could enhance cell viability and level of acetylcholine. AO/EB staining and Mitochondrial membrane potential (MMP) analysis showed that SMP significantly suppressed apoptosis, which may be due to anti-oxidative stress activity. Moreover, the effects of M308 and SMP on expressions of PSEN1, DRD2, and APP mRNA were consistent, and M308 can significantly reverse the expression of PSEN1 and DRD2 mRNA in H2O2-treated PC12 cells. The strategy based on the network could be employed to identify anti-AD compounds from Chinese herbs. Notably, M308 stands out as a promising anti-AD candidate for development.
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Enfermedad de Alzheimer , Medicamentos Herbarios Chinos , Enfermedades Neurodegenerativas , Salvia miltiorrhiza , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Medicamentos Herbarios Chinos/química , Peróxido de Hidrógeno , Simulación del Acoplamiento Molecular , Enfermedades Neurodegenerativas/tratamiento farmacológico , Fitoquímicos/farmacología , ARN Mensajero , Ratas , Salvia miltiorrhiza/químicaRESUMEN
We have found recently that nuclear uptake of the cell-impermeable DNA light-switching Ru(II)-polypyridyl cationic complexes such as [Ru(bpy)2(dppz)]Cl2 was remarkably enhanced by pentachlorophenol (PCP), by forming ion-pairing complexes via a passive diffusion mechanism. However, it is not clear whether the enhanced nuclear uptake of [Ru(bpy)2(dppz)]2+ is only limited to PCP, or it is a general phenomenon for other highly chlorinated phenols (HCPs); and if so, what are the major physicochemical factors in determining nuclear uptake? Here, we found that the nuclear uptake of [Ru(bpy)2(dppz)]2+ can also be facilitated by other two groups of HCPs including three tetrachlorophenol (TeCP) and six trichlorophenol (TCP) isomers. Interestingly and unexpectedly, 2,3,4,5-TeCP was found to be the most effective one for nuclear delivery of [Ru(bpy)2(dppz)]2+, which is even better than the most-highly chlorinated PCP, and much better than its two other TeCP isomers. Further studies showed that the nuclear uptake of [Ru(bpy)2(dppz)]2+ was positively correlated with the binding stability, but to our surprise, inversely correlated with the lipophilicity of the ion-pairing complexes formed between [Ru(bpy)2(dppz)]Cl2 and HCPs. These findings should provide new perspectives for future investigations on using ion-pairing as an effective method for delivering other bio-active metal complexes into their intended cellular targets.
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Núcleo Celular/metabolismo , Clorofenoles/química , ADN/química , Técnicas de Transferencia de Gen , Rutenio/química , ADN/genética , Células HeLa , Humanos , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
With the continuous improvement of people's living standards and the greatly accelerated pace of life, patients' requirements for traditional Chinese medicine(TCM) pharmaceutical care are constantly raised, and personalized TCM preparations used are increasing year by year. However, a series of problems, such as the bottleneck of preparation technology, the lack of preparation specifications, and the weak legal basis for supervision, have become prominent, leading to the uneven product quality of personalized pre-parations. This paper systematically summarized and analyzed the current situation and existing problems of personalized TCM preparations, including dosage form application, preparation technology, production equipment, quality standard, clinical application, and administration mode. Additionally, it put forward an inheritance and innovation research mode of personalized TCM preparation technology based on the physical fingerprint of raw materials and innovation research and intellectual property protection mode of "research-patent-technology-equipment-standard". Furthermore, innovative development strategies were proposed, such as the production standard system of clinical preparations based on the whole process traceability and the regional processing service mode of clinical preparations based on industry 4.0. The present study is expected to provide beneficial references for the inheritance and innovation development of personalized TCM preparations.
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Productos Biológicos , Medicamentos Herbarios Chinos , Humanos , Medicina Tradicional China , Control de CalidadRESUMEN
Recently, the sulfate radical (SO4â¢-) has been found to exhibit broad application prospects in various research fields such as chemical, biomedical, and environmental sciences. It has been suggested that SO4â¢- could be transformed into a more reactive hydroxyl radical (â¢OH); however, no direct and unequivocal experimental evidence has been reported yet. In this study, using an electron spin resonance (ESR) secondary radical spin-trapping method coupled with the classic spin-trapping agent 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and the typical â¢OH-scavenging agent dimethyl sulfoxide (DMSO), we found that â¢OH can be produced from three SO4â¢--generating systems from weakly acidic (pH = 5.5) to alkaline conditions (optimal at pH = 13.0), while SO4â¢- is the predominant radical species at pH < 5.5. A comparative study with three typical â¢OH-generating systems strongly supports the above conclusion. This is the first direct and unequivocal ESR spin-trapping evidence for â¢OH formation from SO4â¢- over a wide pH range, which is of great significance to understand and study the mechanism of many SO4â¢--related reactions and processes. This study also provides an effective and direct method for unequivocally distinguishing â¢OH from SO4â¢-.
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Óxidos N-Cíclicos , Radical Hidroxilo , Espectroscopía de Resonancia por Spin del Electrón , Radicales Libres , Concentración de Iones de Hidrógeno , Marcadores de Spin , SulfatosRESUMEN
Microecology was directly or indirectly involved in the growth and development, metabolism process, and component accumulation of traditional Chinese medicine(TCM) in various ways, which affected the formation and changes of the geoherbalism of TCM. It was one of the main tasks of traditional Chinese medical microecology(TCMM) to reveal the relationship among microecological structure and its change rule and the quality effect of TCM. The heterogeneity of soil environment caused by geographical and climatic factors, as well as the discreteness limitation caused by isolation factors such as distance and host selection, were the main causes of the differentiation of microecological geography of TCM. The microecology of TCM had important influences and contributions on the distinctive origin and quality of Dao-di herbs, which was mainly reflected in the formation of excellent germplasm(including disease and insect resistance, drought resistance, salt resistance, cold resistance, etc.), the increase of yield, the formation of medicinal parts, the metabolism and accumulation of effective components, the time limit of harvesting, and the toxicity, increasing efficiency or reducing toxicity of TCM in the processing, the changes of product efficiency after introduction, and the authenticity of fungus medicine. With the vigorous development of metabonomics and modern information technology, the following aspects would become the future research trends, including the microecologically mediated biogenic pathway of chemical components, the metabolic synthesis reactor of TCM based on the microecological quantitative effect relationship, the cultivation of genuine Chinese medicine based on reconstruction of microecological structure, the origin identification barcode traceability technology, and the toxicity reduction and efficiency enhancement technology of TCM based on the microecological.
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Medicamentos Herbarios Chinos , Geografía , Suelo/química , Clima , Medicina Tradicional China , MetabolómicaRESUMEN
Degeneration of the intervertebral disc (IVD) is a leading source of chronic low back pain or neck pain, and represents the main cause of long-term disability worldwide. In the aim to relieve pain, total disc replacement (TDR) is a valuable surgical treatment option, but the expected benefit strongly depends on the prosthesis itself. The present contribution is focused on the synthetic mimic of the native IVD in the aim to optimally restore its functional anatomy and biomechanics, and especially its time-dependency. Semi-crystalline polyethylene (PE) materials covering a wide spectrum of the crystallinity are used to propose new designs of TDR. The influence of the crystallinity on various features of the time-dependent mechanical response of the PE materials is reported over a large strain range by means of dynamic mechanical thermo-analysis and video-controlled tensile mechanical tests. The connection of the stiffness and the yield strength with the microstructure is reported in the aim to propose a model predicting the crystallinity dependency of the response variation with the frequency. New designs of TDR are proposed and implemented into an accurate computational model of a cervical spine segment in order to simulate the biomechanical response under physiological conditions. Predicted in-silico motions are found in excellent agreement with experimental data extracted from published in-vitro studies under compression and different neck movements, namely, rotation, flexion/extension and lateral bending. The simulation results are also criticized by analyzing the local stresses and the predicted biomechanical responses provided by the different prosthetic solutions in terms of time-dependency manifested by the hysteretic behavior under a cyclic movement and the frequency effect.
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Fenómenos Biomecánicos/fisiología , Sustitutos de Huesos/química , Disco Intervertebral , Polietileno/química , Diseño de Prótesis , Reeemplazo Total de Disco , Alquenos/química , Cristalización , Pruebas de Dureza , Humanos , Disco Intervertebral/química , Disco Intervertebral/cirugía , Vértebras Lumbares , Ensayo de Materiales , Polietilenos/química , Polímeros/química , Rango del Movimiento Articular/fisiología , Estrés Mecánico , Factores de Tiempo , Reeemplazo Total de Disco/instrumentación , Reeemplazo Total de Disco/métodos , Soporte de Peso/fisiologíaRESUMEN
In the long-term evolution, microbes and hosts coexist widely, forming a symbiotic microecosystem and resulting the complex interactions of the metabolism. With the application of microecological theory in Chinese materia medica science, two main points have been accepted gradually. On the one hand, the prevention and treatment of human diseases by traditional Chinese medicines can be achieved through the correction and adjustment of the imbalance of the human microecosystem. On the other hand, the microecosystem can regulate the quality of traditional Chinese medicines in real time, and further affect their curative effect. Thus, a new discipline, Traditional Chinese Medical Microecology, has been gradually established. In this review, the background, theoretical structure, research directions, key problems and the relationship with human microecology of Traditional Chinese Medical Microecology were systematically summarized and prospected for promoting its development. Moreover, this review provides a reference protocol for further discoursing the microecological mechanism involving the efficacy of traditional Chinese medicines.
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Materia Medica , Medicina Tradicional China , Microbiota , Humanos , InvestigaciónRESUMEN
OBJECTIVE: To observe the effects of L-carnitine treatment on serum levels of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) and cardiac function in children with heart dysfunction and severe hand-foot-mouth disease (HFMD). METHODS: A total of 120 children with severe HFMD were enrolled and randomly and equally divided into routine treatment group and L-carnitine treatment group. Thirty healthy children served as the control group. HFMD patients were given anti-fever and antiviral treatment as the basic treatment, while the patients in the L-carnitine treatment group were given L-carnitine as an adjuvant treatment to the basic treatment. Treatment outcomes were observed in the two groups. For all the subjects, serum levels of BNP and NT-proBNP and cardiac function parameters including left ventricular ejection fraction (LVEF), fractional shortening (FS), and cardiac index (CI) were measured at different time points before and after treatment. RESULTS: Before treatment, HFMD patients had significantly higher serum levels of BNP and NT-proBNP and heart rate but significantly lower LVEF, FS, and CI compared with the control group (P<0.05). After treatment, the L-carnitine treatment group had a significantly higher response rate than the routine treatment group (P<0.05). After 3 days of treatment, the serum levels of BNP and NT-proBNP, LVEF, FS, and CI were significantly reduced in the L-carnitine group (P<0.05); the L-carnitine group had significantly lower serum levels of BNP and NT-proBNP, LVEF, FS, and CI than the routine treatment group (P<0.05); there were no significant differences in the serum levels of BNP and NT-proBNP, LVEF, FS, or CI between the L-carnitine treatment and control groups (P>0.05). After 5 days of treatment, there were no significant differences in the serum levels of BNP and NT-proBNP, LVEF, FS, or CI between the L-carnitine treatment and routine treatment groups (P>0.05). Heart rate recovery was significantly slower in the routine treatment group than in the L-carnitine treatment group (P<0.05). CONCLUSIONS: As an adjuvant therapy for severe HFMD, L-carnitine treatment has satisfactory short-term efficacy in reducing the serum levels of BNP and NT-proBNP and improving cardiac function, thus improving clinical outcomes.
Asunto(s)
Carnitina/administración & dosificación , Enfermedad de Boca, Mano y Pie/tratamiento farmacológico , Enfermedad de Boca, Mano y Pie/fisiopatología , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Biomarcadores/sangre , Preescolar , Femenino , Enfermedad de Boca, Mano y Pie/sangre , Corazón/efectos de los fármacos , Corazón/fisiopatología , Pruebas de Función Cardíaca , Humanos , Lactante , Masculino , Resultado del Tratamiento , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
In the present work, a series of low-temperature firing scheelite structured microwave dielectric in water-insoluble La2O3-Nb2O5-V2O5 system was prepared via the traditional solid-state reaction method. Backscattering electron diffraction, X-ray diffraction (XRD), energy-dispersive analysis, and Rietveld refinements were performed to study the phase evolution and crystal structure. In the full composition range of (1 - x)LaNbO4-xLaVO4 (0 ≤ x ≤ 0.9) ceramics, at least four typical phase regions including monoclinic fergusonite, tetragonal sheelite, B-site ordered sheelite, and composite of monoclinic LaVO4 and tetragonal sheelite phases can be detected according to XRD analysis. The variations of relative dielectric constant εr, quality factor Q × f, and resonant frequency τf could be attributed to Nb/V-O bond ionicity, lattice energy, and the coefficient of thermal expansion. Infrared reflectivity spectra analysis revealed that ion polarization contributed mainly to the permittivity in microwave frequencies ranges. Furthermore, the 0.7LaNbO4-0.3LaVO4 ceramic sintered at 1160 °C possessed excellent microwave dielectric properties with an εr of â¼17.78, a Q × f of â¼75â¯940 GHz, and a τf of ca. -36.8 ppm/°C. This series of materials might be good candidate for microwave devices.