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1.
J Ethnopharmacol ; 253: 112658, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32035876

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Many bioactive constituents of Chinese herbal medicines have poor oral bioavailability. Besides oral administration, herbal medicines in China are also prepared for parenteral administration. Unlike for intravenous route, little is known about the intramuscular pharmacokinetics of herbal compounds. To facilitate rational use of herbal medicine, it is important to better understand such intramuscular pharmacokinetics. AIM OF THE STUDY: Bioactive constituents of XueShuanTong (a lyophilized extract of Panax notoginseng roots, extensively used in treatment of ischemic heart and cerebrovascular diseases) predominantly comprise ginsenosides Rb1 and Rd of 20(S)-protopanaxadiol-type and ginsenosides Rg1, and Re, and notoginsenoside R1 of 20(S)-protopanaxatriol-type; these saponins are poorly absorbed from the gastrointestinal tract. This study aimed to compare intramuscular and intravenous pharmacokinetics of these ginsenosides after dosing XueShuanTong. METHODS: Pharmacokinetics of ginsenosides was assessed in human volunteers receiving an intramuscular injection or 1.5-h intravenous infusion of XueShuanTong, both at 150 mg/person, and the plasma and urine samples were analyzed by liquid chromatography/mass spectrometry. RESULTS: Like after intravenous administration, the unchanged saponins were the major circulating forms after intramuscular administration, while their metabolites were poorly detected. These ginsenosides exhibited intramuscular bioavailability of 100%-112%, relative to the respective intravenous data. Similar to that after intravenous infusion, the 20(S)-protopanaxadiol-type ginsenosides after the intramuscular injection exhibited notably longer terminal half-lives (46-106 h) than the 20(S)-protopanaxatriol-type ginsenosides (1.1-1.4 h). CONCLUSIONS: Intramuscular route might be an effective alternative to intravenous route for XueShuanTong, from the pharmacokinetic perspective.

2.
DNA Cell Biol ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031891

RESUMO

Colon adenocarcinoma (COAD) is a common noncutaneous carcinoma worldwide with high morbidity and mortality. Effective prevention methods are far from being met. Both diagnostic and prognostic models that can precisely and accurately predict the status and survival time of COAD are urgently needed. In the field of COAD, there have been limited studies on molecular biomarkers that can predict disease status and prognosis. Hence, an important task is to identify these biomarkers. We aimed to identify important risk genes that have the ability not only to diagnose tumors but also to predict overall survival. A comprehensive analysis was performed in this study. Finally, carbonic anhydrase 1 (CA1) and CA4 were identified as potential biomarkers due to their predictive roles in diagnosis and prognosis, and the results were further confirmed by a series of analyses. Overall, these findings are of great importance and may facilitate individualized treatment in diagnosis and prognosis.

3.
ACS Appl Mater Interfaces ; 12(5): 5932-5938, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31916741

RESUMO

The development of high-performance electrode materials is of great significance for the next-generation room-temperature sodium-ion batteries. In this work, a new Na super-ionic conductor (NASICON) negative electrode, AgTi2(PO4)3, is prepared by a facile solid-state reaction and employed as a sodium storage material for the first time. In situ X-ray diffraction during battery operation reveals an electrochemically Ag nanoparticle coating mechanism upon sodiation, facilitating the electron transfer in the complex. In addition, two steps of highly reversible biphasic transformation are observed. As a result, a reversible capacity of 214.9 mA h g-1 can be achieved, corresponding to the insertion/extraction of nearly four sodium ions. The AgTi2(PO4)3 electrode also demonstrates better kinetic properties than the bare NaTi2(PO4)3 material. Such an "in situ" decorating method can open up a new direction for the design of NASICON-structured materials.

4.
Clin Pharmacol Ther ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31868917

RESUMO

Drug safety is a severe clinical pharmacology and toxicology problem that has caused immense medical and social burdens every year. Regretfully, there still misses a reproducible method to assess drug safety systematically and quantitatively. In this study, we developed an advanced machine learning model for de novo drug safety assessment by solving the multilayer drug-gene-adverse drug reaction (ADR) interaction network. For the first time, the drug safety was assessed in a broad landscape of 1,156 distinct ADRs. We also designed a parameter ToxicityScore to quantify the overall drug safety. Moreover, we determined association strength for every 3,807,631 gene-ADR interactions, which clues mechanistic exploration of ADRs. For convenience, we deployed the model as a web service ADRAlert-gene at http://www.bio-add.org/ADRAlert/. In summary, this study offers insights into prioritizing safe drug therapy. It helps to reduce the attrition rate of new drug discovery by providing reliable ADR profile in early pre-clinical stage.

5.
Radiol Case Rep ; 14(11): 1382-1384, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31695825

RESUMO

A 13-year-old female patient presented with chest pain had no history of heart disease or trauma. She was finally diagnosed with the interrupted aortic arch by 320-slice CT angiography, without intracardial malformations or patent ductus arteriosus. Her descending aortic blood was supplied by plentiful collateral circulation on the chest. According to literature reports, patients with complete interruption of the aortic arch rarely live 10 years without surgical intervention. More particularly, this case does not fit the current classification systems.

6.
Phys Chem Chem Phys ; 21(47): 25940-25944, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31728475

RESUMO

The boundary between a capacitor and a battery is vague for layered transition metal sulfides, especially when it comes to TiS2 with a multi-phase transition process. In this work we analyzed both the quasi-static process and dynamic process of K+ storage in TiS2 with carbonate based electrolytes, which proved to be an intercalation pseudocapacitive behavior.

7.
Sci Rep ; 9(1): 14549, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601925

RESUMO

We assessed the three-dimensional (3D) pattern of the physiologic drift of the remaining adjacent teeth after premolar extraction due to orthodontic reasons and the associated factors. Data were collected from 45 patients aged 17.04 ± 5.14 years who were scheduled to receive a fixed appliance after maxillary premolar extraction. Seventy-five drift models were obtained and digitalized via 3D scanning. The average physiologic drift duration was 81.66 ± 70.03 days. Angular and linear changes in the first molars, second premolars, and canines were measured using the 3D method. All the examined teeth had tipped and moved towards the extraction space, leading to space decreases. Posterior teeth primarily exhibited significant mesial tipping and displacement, without rotation or vertical changes. All canine variables changed, including distal inward rotation and extrusion. The physiologic drift tended to slow over time. Age had a limited negative effect on the mesial drift of posterior teeth, whereas crowding had a limited positive effect on canine drift. Thus, the mesial drift of molars after premolar extraction may lead to molar anchorage loss, particularly among younger patients. The pattern of the physiologic drift of maxillary canines can help relieve crowding and facilitate labially ectopic canine alignment, whereas canine drift is accelerated by more severe crowding.

8.
Phys Rev Lett ; 123(8): 086601, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31491218

RESUMO

We investigate the magnetic phase diagram of a solid solution BaFe_{2}(S_{1-x}Se_{x})_{3}, which is categorized into a new family of Fe-based superconductors hosting a quasi-one-dimensional ladder lattice. We show that the antiferromagnetic order is largely suppressed due to bicritical fluctuations in the vicinity of the magnetic transition at x=0.23 from the stripe-type to block-type ordering. Moreover, we observed large magnon contributions in the thermal conductance in a wide x range. These results indicate the quasi-one-dimensional nature of spin systems and give a solid foundation for modeling the material toward unraveling the microscopic mechanism of superconductivity.

9.
Polymers (Basel) ; 11(8)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382416

RESUMO

Thermoelectric (TE) generators consisting of flexible and lightweight p- and n-type single-walled carbon nanotube (SWCNT)-based composites have potential applications in powering wearable electronics using the temperature difference between the human body and the environment. Tuning the TE properties of SWCNTs, particularly p- versus n-type control, is currently of significant interest. Herein, the TE properties of SWCNT-based flexible films consisting of SWCNTs doped with polyethyleneimine (PEI) were evaluated. The carrier type of the SWCNT/PEI composites was modulated by regulating the proportion of SWCNTs and PEI using simple mixing techniques. The as-prepared SWCNT/PEI composite films were switched from p- to n-type by the addition of a high amount of PEI (>13.0 wt.%). Moreover, interconnected SWCNTs networks were formed due to the excellent SWNT dispersion and film formation. These parameters were improved by the addition of PEI and Nafion, which facilitated effective carrier transport. A TE generator with three thermocouples of p- and n-type SWCNT/PEI flexible composite films delivered an open circuit voltage of 17 mV and a maximum output power of 224 nW at the temperature gradient of 50 K. These promising results showed that the flexible SWCNT/PEI composites have potential applications in wearable and autonomous devices.

10.
Nat Commun ; 10(1): 3227, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324815

RESUMO

The interactions between charge carriers and electrode structures represent one of the most important considerations in the search for new energy storage devices. Currently, ionic bonding dominates the battery chemistry. Here we report the reversible insertion of a large molecular dication, methyl viologen, into the crystal structure of an aromatic solid electrode, 3,4,9,10-perylenetetracarboxylic dianhydride. This is the largest insertion charge carrier when non-solvated ever reported for batteries; surprisingly, the kinetic properties of the (de)insertion of methyl viologen are excellent with 60% of capacity retained when the current rate is increased from 100 mA g-1 to 2000 mA g-1. Characterization reveals that the insertion of methyl viologen causes phase transformation of the organic host, and embodies guest-host chemical bonding. First-principles density functional theory calculations suggest strong guest-host interaction beyond the pure ionic bonding, where a large extent of covalency may exist. This study extends the boundary of battery chemistry to large molecular ions as charge carriers and also highlights the electrochemical assembly of a supramolecular system.

11.
J Integr Plant Biol ; 61(11): 1114-1120, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31267663

RESUMO

By using mechanical and optical sectioning of DII/mDII and R2D2 auxin sensors, we reconfirmed the presence of asymmetric auxin signaling in leaf primordia. We also showed that the imaging data reported by Bhatia et al. (2019) may suffer from artefacts, and that their analysis was artificially biased due to an arbitrary domain demarcation.

12.
Schizophr Res ; 209: 64-71, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31101514

RESUMO

BACKGROUND: White matter (WM) abnormalities are amongst the most commonly described neuroimaging findings in patients with psychotic disorders including schizophrenia (SZ) and bipolar disorder (BD), and may be central to pathophysiology. Few studies have directly compared WM abnormalities in patients with SZ and BD in the first episode of illness, and no studies to date have attempted to separate abnormalities of axon and myelin using complementary MRI techniques. METHODS: We examined WM abnormalities in young adults with SZ (n = 19) or BD (n = 16) within the first year of illness onset, and healthy controls (n = 22) using a combination of diffusion tensor spectroscopy to measure NAA, creatine (Cr), and choline (Cho), and magnetization transfer ratio (MTR). MTR reflects myelin content, NAA diffusion is neuron specific, and Cr and Cho diffusion reflect both neuron and glial signal. RESULTS: We found no differences in MTR or NAA ADC in either patient group compared to controls, but significant elevations of both Cr and Cho diffusion in patients with SZ, and elevations of Cho diffusion in patients with BD. Elevations in Cr and Cho diffusion in the absence of NAA diffusion abnormalities indicate that the aberrant signal arises in glia. CONCLUSIONS: Glial abnormalities were present and detectable by the first episode of psychosis, whereas major abnormalities in axon and myelin were not. Examination of these neurobiological markers early in the course of illness may clarify the neuroprogressive nature of these distinct aspects of WM, and their associations with early clinical phenotypes.

13.
Alzheimer Dis Assoc Disord ; 33(2): 170-178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31033517

RESUMO

OBJECTIVE: The purpose of this meta-analysis was to evaluate the therapeutic effect of transcranial direct current stimulation (tDCS) on mild to moderate Alzheimer disease (AD) patients. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched until April 2018. The primary cognitive outcomes were extracted from included articles. A crude standardized mean difference with 95% CI was calculated by using fixed or random effect models. RESULTS: Seven studies with 146 patients were included in this meta-analysis. The pooled result showed that tDCS significantly improved cognitive function of AD patients (standardized mean difference=0.37; 95% CI, 0.09-0.65; P=0.01). Subgroup analyses showed that: a single session of tDCS was significantly effective (P<0.05) whereas repeated sessions of tDCS was not lower current density (0.06 mA/cm) (P>0.05) but not higher current density (0.08 mA/cm) significantly improved cognitive performance; stimulating the temporal cortex (P<0.05) but not the left dorsal lateral prefrontal cortex significantly improved cognitive function of AD patients; and improved cognitive function occurred in the group with higher education (P<0.05) but not in the group with lower education. CONCLUSIONS: Current evidence suggests that tDCS has a beneficial effect in mild to moderate AD patients. We must be cautious about the results of subgroup analysis given small sample sizes, and further well-designed studies with larger sample size are required to verify these results.

14.
Front Psychiatry ; 10: 135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984036

RESUMO

Objective: Repetitive transcranial magnetic stimulation (rTMS) has been applied to dorsolateral prefrontal cortex (DLPFC) to improve cognitive function of patients with schizophrenia (SZs). The aim of this meta-analysis was to evaluate whether a high-frequency rTMS course could enhance cognitive function in SZs. Methods: Studies published in PubMed, Cochrane Library, Embase, ScienceDirect, and Web of science were searched until April 2018. The search terms included: "repetitive transcranial magnetic stimulation" or "Rtms," "SZ," or "schizophrenia," and "neuro-cognition" or "neurocognitive performance" or "cognitive effects" or "cognitive" or "cognition" or "working memory" or "executive function" or "language function" or "processing speed," After screening the literatures according to inclusion and exclusion criteria, extracting data, and evaluating the methodological quality of the included studies, a meta-analysis was performed using RevMan 5.3 software (The Cochrane Collaboration, USA). Results: A total of 9 studies on cognitive dysfunction of SZs were included and involved 351 patients. A significant efficacy of high-frequency rTMS on working memory in SZs was found compared to sham stimulation [p = 0.009, standardized mean difference (SMD) = 0.34]. Specifically, rTMS treatment positioned on the left DLPFC, with a total pluses <30,000 was more significantly more effective in improving the working memory (SMD = 0.33, p = 0.03). No improvement was found in other cognitive domains such as executive function, attention, processing speed, and language function. For the follow-up observations, high-frequency rTMS had long-lasting sustained effects on working memory (SMD = 0.45, p = 0.01) and language function (SMD = 0.77, p = 0.02) in SZs. Conclusions: High-frequency rTMS over the left DLPFC with a total pulses <30,000 stimulation could significantly improve working memory in SZs for an extended period of time.

15.
Nat Commun ; 10(1): 1190, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30867414

RESUMO

Understanding the Vitis species at the genomic level is important for cultivar improvement of grapevine. Here we report whole-genome genetic variation at single-base resolution of 472 Vitis accessions, which cover 48 out of 60 extant Vitis species from a wide geographic distribution. The variation helps to identify a recent dramatic expansion and contraction of effective population size in the domesticated grapevines and that cultivars from the pan-Black Sea region have a unique demographic history in comparison to the other domesticated cultivars. We also find selective sweeps for berry edibility and stress resistance improvement. Furthermore, we find associations between candidate genes and important agronomic traits, such as berry shape and aromatic compounds. These results demonstrate resource value of the resequencing data for illuminating the evolutionary biology of Vitis species and providing targets for grapevine genetic improvement.


Assuntos
Genoma de Planta/genética , Melhoramento Vegetal , Seleção Genética/genética , Vitis/genética , Mar Negro , Domesticação , Europa (Continente) , Extremo Oriente , Frutas/genética , Genótipo , Anotação de Sequência Molecular , América do Norte , Filogenia , Filogeografia , Polimorfismo de Nucleotídeo Único/genética , Sequenciamento Completo do Genoma
17.
Magn Reson Med ; 82(1): 84-94, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30860289

RESUMO

PURPOSE: Glutamate (Glu) is the most abundant neurotransmitter in the human central nervous system and glutamatergic neurotransmission has been implicated in many common and severe neuropsychiatric disorders. In vivo MRS techniques have been developed to measure brain Glu concentration to investigate the pathophysiology of various brain disorders. However, it is difficult to interpret Glu signal changes because Glu plays multiple roles in the brain and is found in multiple microenvironments including cytosolic, vesicular, and extracellular. METHODS: In vivo diffusion-weighted MRS (DW-MRS) with low to very high b-values was performed on the rat prefrontal cortex at 9.4T under both light and deep anesthetic conditions to examine Glu diffusion properties. RESULTS: Significant alterations in Glu diffusion as well as reduced Glu concentration were observed under deep anesthesia compared with superficial anesthesia in the absence of similar changes in NAA or creatine. CONCLUSION: The modifications in Glu diffusion under deep anesthesia might reflect changes in Glu microenvironment. The present work shows that Glu DW-MRS could be an important tool to explore Glu physiology with changing levels of neuronal activity and synaptic function.

18.
PLoS Biol ; 17(2): e3000134, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30735499

RESUMO

Microglia are resident immune cells that play critical roles in maintaining the normal physiology of the central nervous system (CNS). Remarkably, microglia have an intrinsic capacity to repopulate themselves after acute ablation. However, the underlying mechanisms that drive such restoration remain elusive. Here, we characterized microglial repopulation both spatially and temporally following removal via treatment with the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622. We show that microglia were replenished via self-renewal, with no contribution from nonmicroglial lineages, including Nestin+ progenitors and the circulating myeloid population. Interestingly, spatial analyses with dual-color labeling revealed that newborn microglia recolonized the parenchyma by forming distinctive clusters that maintained stable territorial boundaries over time, indicating the proximal expansive nature of adult microgliogenesis and the stability of microglia tiling. Temporal transcriptome profiling at different repopulation stages revealed that adult newborn microglia gradually regain steady-state maturity from an immature state that is reminiscent of the neonatal stage and follow a series of maturation programs, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, interferon immune activation, and apoptosis. Importantly, we show that the restoration of microglial homeostatic density requires NF-κB signaling as well as apoptotic egress of excessive cells. In summary, our study reports key events that take place from microgliogenesis to homeostasis reestablishment.


Assuntos
Envelhecimento/genética , Encéfalo/metabolismo , Homeostase/genética , Microglia/metabolismo , NF-kappa B/genética , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Envelhecimento/metabolismo , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Apoptose/genética , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Interferons/genética , Interferons/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microglia/citologia , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Nestina/genética , Nestina/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurogênese/efeitos dos fármacos , Neurogênese/genética , Compostos Orgânicos/toxicidade , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Receptores do Fator de Crescimento Derivado de Plaquetas/genética , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Regeneração/genética , Transdução de Sinais , Transcriptoma
19.
Pestic Biochem Physiol ; 154: 7-16, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30765059

RESUMO

Benzothiazole (BZO) is an antimicrobial secondary metabolite volatilized by many plants and microbes. However, the mechanism of BZO against phytopathogens is still unclear. Here, we found that BZO has antimicrobial activity against the oomycete pathogen Phytophthora capsici. Transcriptome and proteome analyses demonstrated that BZO significantly suppressed the expression of genes and proteins involved in morphology, abiotic stress defense and detoxification, but induced the activity of apoptosis. Annexin V-FITC/PI staining confirmed that the process of apoptosis was significantly induced by BZO at concentration of 150 mg L-1. FITC-phalloidin actin-cytoskeleton staining combined with hyphal cell wall staining and hyphal ultrastructure studies further confirmed that BZO disrupted the cell membrane and hyphal morphology through disrupting the cytoskeleton, eventually inhibiting the growth of hyphae. These data demonstrated that BZO has multiple modes of action and may act as potential leading compound for the development of new oomycete fungicides. These results also showed that the combination of transcriptomic and proteomic approaches was a useful method for exploring the novel antifungal mechanisms of natural compounds.


Assuntos
Antifúngicos/farmacologia , Benzotiazóis/farmacologia , Phytophthora/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proteínas Fúngicas/genética , Hifas/efeitos dos fármacos , Hifas/fisiologia , Hifas/ultraestrutura , Inativação Metabólica , Microscopia Eletrônica de Transmissão , Phytophthora/fisiologia , Phytophthora/ultraestrutura , Proteoma , Estresse Fisiológico , Transcriptoma/efeitos dos fármacos
20.
Angew Chem Int Ed Engl ; 58(16): 5286-5291, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30801922

RESUMO

We report reversible electrochemical insertion of NO3 - into manganese(II, III) oxide (Mn3 O4 ) as a cathode for aqueous dual-ion batteries. Characterization by TGA, FTIR, EDX, XANES, EXAFS, and EQCM collectively provides unequivocal evidence that reversible oxidative NO3 - insertion takes place inside Mn3 O4 . Ex situ HRTEM and corresponding EDX mapping results suggest that NO3 - insertion de-crystallizes the structure of Mn3 O4 . Kinetic studies reveal fast migration of NO3 - in the Mn3 O4 structure. This finding may open a new direction for novel low-cost aqueous dual-ion batteries.

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