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BACKGROUND: The study was designed to explore the correlation of the asymmetric regulation between periaqueductal gray (PAG) and bilateral trigeminal nucleus caudalis (TNC) in migraine rats through studying the changes of metabolites in pain regulatory pathway of acute migraine attack. METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into three groups: blank, control, model groups. Then, blank group was intraperitoneally injected with ultrapure water, while control group injected with saline and model group injected with Glyceryl Trinitrate (GTN). Two hours later, PAG and bilateral TNC were removed respectively, and metabolite concentrations of PAG, Left-TNC, Right-TNC were obtained. Lastly, the differences of metabolite among three brain tissues were compared. RESULTS: The relative concentrations of rNAA, rGlu, rGln, rTau, rMI in PAG or bilateral TNC had interaction effects between groups and sites. The concentration of rLac of three brain tissues increased in migraine rats, however, the rLac of LTNC and RTNC increased more than that of PAG. Besides, the concentrations of rNAA and rGln increased in RTNC, while rGABA decreased in RTNC. CONCLUSIONS: There is correlation between PAG, LTNC and RTNC in regulation of pain during acute migraine attack, and the regulation of LTNC and RTNC on pain is asymmetric.
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Transtornos de Enxaqueca , Substância Cinzenta Periaquedutal , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Transtornos de Enxaqueca/metabolismo , Dor/metabolismo , Núcleos do TrigêmeoRESUMO
BACKGROUND: The hypothalamus plays a central role in the pathophysiology of migraine and is considered to be the "migraine generator." It participates in initiating a migraine attack through its connectivity to regions of the brain involved in processing and modulating pain. However, the underlying mechanisms of hypothalamic effective functional connectivity that bring about migraines remain unclear. This study investigated the hypothalamus-based directional effective connectivity in migraine without aura patients and assessed associations among the clinical characteristics. METHODS: Seven patients with migraine without aura during the attack (MWoA-DA) (four with photophobia (MWoA-DAWP) and three without photophobia (MWoA-DAWoP)), twenty-seven patients with migraine without aura during the interictal period (MWoA-DI), and twenty-nine healthy controls (HC) were included in this study. Granger causality analysis (GCA) was used to investigate the directional effective connectivity between the hypothalamus and other brain regions. RESULTS: MWoA-DA patients exhibited decreased outflow from the bilateral hypothalamus to the visual cortex compared with the MWoA-DI patients and HCs. The MWoA-DAWP group primarily contributed to this result. The MWoA-DA patients showed decreased outflow from the bilateral hypothalamus to the right inferior parietal gyrus compared with the HCs. The visual analogue scale (VAS) was negatively correlated with abnormal effective functional connectivity from the right hypothalamus to the right inferior parietal gyrus in the MWoA-DA group. CONCLUSIONS: These data provide evidence that the hypothalamus might serve as a central component of a multisystem network implicated in migraine and ictal photophobia, which includes hypothalamus and the visual and trigeminovascular systems.
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Enxaqueca sem Aura , Encéfalo/diagnóstico por imagem , Humanos , Hipotálamo/diagnóstico por imagem , Imageamento por Ressonância Magnética , FotofobiaRESUMO
There are few reports of rhabdomyolysis caused by anticoagulants, and it is extremely rare for it to be caused by dabigatran etexilate. An 86-year-old female experienced sudden muscle weakness and pain, a significant increase in Creatine kinase, and renal impairment after oral administration of dabigatran etexilate for 3 weeks. The enhanced thigh MRI showed abnormal signal in multiple thigh muscle groups, indicating that the lesions should be considered inflammatory diseases. In conclusion, the possibility of rhabdomyolysis should be ruled out when muscle weakness and myalgia occur at the beginning of dabigatran etexilate treatment.
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Dabigatrana , Rabdomiólise , Idoso de 80 Anos ou mais , Benzimidazóis/efeitos adversos , Dabigatrana/efeitos adversos , Feminino , Humanos , Debilidade Muscular , Piridinas/efeitos adversos , Rabdomiólise/induzido quimicamente , Rabdomiólise/diagnóstico por imagemRESUMO
BACKGROUND: Idiopathic hypereosinophilic syndrome (IHES) is associated with various organ system dysfunctions. Neurologic abnormalities have been previously noted in this syndrome. Cerebral infarction secondary to occlusion of large cerebral artery is rarely reported. Here we described a patient with IHES presented progressive multiple cerebral infarctions caused by bilateral middle cerebral artery occlusion. CASE PRESENTATION: A 55-year-old Chinese woman presented to our hospital with acute onset of right limbs weakness and slurred speech. Laboratory tests showed a significant eosinophilia of 5.29 × 109/L (normal, < 0.5), 49.9% of leukocytes. Brain magnetic resonance imaging (MRI) revealed multiple acute cerebral ischemic lesions. Magnetic resonance angiography (MRA) demonstrated stenosis in horizontal segment of right middle cerebral artery. A pretibial skin biopsy revealed eosinophilic infiltration around the capillaries in deep dermis and adipose tissue. The patient was given oral dual anti platelet agents and intravenous methylprednisolone. However, one week later, the patient presented significant neurological deterioration with right-sided hemiparesis and totally motor aphasia. Brain MRI and computed tomography perfusion (CTP) demonstrated new acute cerebral ischemia in left hemisphere. Digital subtraction angiography (DSA) revealed left middle cerebral artery completely occluded. The patient received a high-dose of intravenous methylprednisolone 500 mg per day and the eosinophil count quickly fell to normal within 2 days. She was transferred to a rehabilitation center and her neurological symptoms improved with modified Ranking Scale from 4 to 2. CONCLUSIONS: IHES is one of the rare causes of acute ischemic stroke with large cerebral artery occlusion. An early high-dose of corticosteroids therapy should be considered in cases of IHES patients. Our case study is benefit to clinical diagnosis and treatment of cerebral infarction with IHES.
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Isquemia Encefálica/etiologia , Síndrome Hipereosinofílica/complicações , Infarto da Artéria Cerebral Média/etiologia , Acidente Vascular Cerebral/etiologia , Angiografia Digital , Feminino , Humanos , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/tratamento farmacológico , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Wilson's disease (WD) is an autosomal recessive genetic disease linked to ATP7B, which is located on the chromosome 13q14.3. We presently report a hepatolenticular degeneration carrier whose clinical phenotype mainly included limb weakness and tremor with a novel WD mutation. The mutation in Exon 10 of ATP7B Gene [c.2480G>A p. (Arg827Gln)] was identified after gene sequencing. We have provided diagnostic analyses, such as muscle biopsy and electrophysiology, which would be helpful to deepen the understanding of the pathogenesis underneath nerve damage in WD heterozygote carriers (Hzc).
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ATPases Transportadoras de Cobre/genética , Degeneração Hepatolenticular/genética , Debilidade Muscular/genética , Tremor/genética , Adulto , Povo Asiático/genética , Heterozigoto , Humanos , Masculino , Mutação , FenótipoRESUMO
This work reports on a modularized electrochemical method for the determination of the hormones cortisol, progesterone, testosterone and 17ß-estradiol in urine. These hormones were employed as templates when generating molecular imprints from aniline and metanilic acid by electropolymerization on the surface of screen-printed electrodes. The electrically conductive imprint was characterized by SEM, AFM and cyclic voltammetry. A four-channel system was then established to enable simultaneous determination of the hormones by cyclic voltammetry. The detection limits for cortisol, progesterone, testosterone and 17ß-estradiol are as low as 2, 2.5, 10 and 9 ag·mL-1 (for S/N = 3). Graphical abstract A four-channel system was established to enable simultaneous determination of 4 steroid hormones by cyclic voltammetry and by using moleculalry imprinted polymers.
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Técnicas Eletroquímicas/métodos , Estradiol/urina , Hidrocortisona/urina , Polímeros/química , Progesterona/urina , Testosterona/urina , Compostos de Anilina/química , Técnicas Eletroquímicas/instrumentação , Eletrodos , Desenho de Equipamento , Humanos , Limite de Detecção , Impressão Molecular , Polimerização , Polímeros/síntese química , Ácidos Sulfanílicos/químicaRESUMO
Capillary isoelectric focusing directly coupled to high resolution mass spectrometry (cIEF-MS) provides information on amphoteric molecules, including isoelectric point and accurate mass, which enables structural interrogation of biopolymer pI variants. The coupling of cIEF with MS was facilitated by a flow-through microvial interface, made by stainless steel with high chemical resistance and mechanical robustness. Two on-column electrolyte configurations of cIEF-MS were demonstrated using peptide and protein pI markers. The pI resolution was 0.02 pH unit in the pH range of 5.5 to 7.0, with no anticonvective reagent (glycerol) added. High resolution Orbitrap detector provides mass spectra for midsized proteins (<30 kDa), enabling deconvolution with high accuracy for IEF-focused low abundance species. Charge heterogeneity of therapeutic monoclonal antibodies (mAb) is one of the most important attributes in the biopharmaceutical industry, and it is routinely monitored by IEF and fractionation-based methods. As a proof of concept, the commercial formulation of infliximab was directly analyzed using cIEF-MS for separation and online identification of mAb charge variants. The main intact antibody species along with two basic and one acidic variants were observed, and their accurate molecular weights ( Mw) recorded by MS detector readily revealed the structural differences of these variants. Variants with 0.1 unit in pI difference and 1 Da difference in molecular weight were readily resolved. The deconvoluted intact Mw values showed ppm level accuracy compared to theoretical predictions.
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Anticorpos Monoclonais/análise , Eletroforese Capilar/instrumentação , Focalização Isoelétrica/instrumentação , Espectrometria de Massas/instrumentação , Peptídeos/análise , Proteínas/análise , Desenho de Equipamento , Glicerol/química , Concentração de Íons de Hidrogênio , Infliximab/análise , Ponto IsoelétricoRESUMO
RATIONALE: In medicine and drug development, molecular modelling is an important tool. It is attractive to develop a platform connecting the theoretical structural modelling and the results from experimental measurement. In addition, the separation and structural analysis of bioactive constituent isomers are still challenging tasks. METHODS: Drift tube ion mobility (IM) mass spectrometry (MS) provides the experimental collision cross section (CCS) which contains the structural information. The experimental CCS can be compared with the calculated CCS of the molecular modelling structures. This technique is especially useful for bioactive constituents in herbal medicine because active isomers with the same chemical formula are common in these samples. IM helps separate and identify these isomers and reveals details about their structures and conformations. RESULTS: Two model bioactive constituents, caffeoylquinic acids (CQAs) and dicaffeoylquinic acids (di-CQAs), were selected to systematically investigate the influence of solution, ion source conditions and ion heating on the isomer CCS distributions. By comparing the calculated CCS with the experimental value, we identified the favorable conformations of CQAs. The most compact conformation of a CQA was less likely to isomerize than the more extended conformation. It was found that the isomerization tendency was in accord with the conformation favorability. CONCLUSIONS: This study offers an effective approach to predict and demystify the conformation and isomerization of the active constituents in herbal medicines.
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Plantas Medicinais/química , Ácido Quínico/análogos & derivados , Espectrometria de Massas por Ionização por Electrospray/métodos , Cromatografia Líquida de Alta Pressão/métodos , Isomerismo , Modelos Moleculares , Conformação Molecular , Ácido Quínico/químicaRESUMO
RATIONALE: Quadrupole-based tandem mass spectrometry (MS/MS) plays a critical role in 'omics' studies. However, when a particular m/z precursor is selected by the quadrupole, ions other than the precursor are not transmitted through, and the sensitivity and dynamic range thus diminish. Therefore, separation techniques such as ion mobility (IM) are coupled with MS/MS to improve it. METHODS: In this workflow, every IM-mass spectrometry (MS) scan was followed by one high-voltage collision energy (CE) scan. The precursors were separated in IM drift time and dissociated after IM; the four-dimensional molecular feature extraction (4D MFE) algorithm was used to align the precursors and their MS/MS spectra based on retention time and drift time distribution. A complicated peptide mixture was selected to exemplify the workflow in a proteomics study. RESULTS: The new IM-MS-based workflow achieved similar performance in finding proteins compared to the traditional quadrupole-based MS/MS method. However, a significant difference was found between the proteins found by these two methods. For the four concentration levels analyzed, at least 23% more proteins were found by combining the new methods than only using the traditional quadrupole-based MS/MS method. CONCLUSIONS: The established workflow used the 4D MFE algorithm to analyze a complicated 4D dataset and was demonstrated to find more proteins not found by the traditional quadrupole-based MS/MS method in proteomics application. It is thus an important complementary MS/MS mode for 'omics' studies. Copyright © 2016 John Wiley & Sons, Ltd.
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Proteômica/métodos , Espectrometria de Massas em Tandem/métodos , Algoritmos , Cromatografia Líquida , Proteínas/análise , Proteínas/químicaRESUMO
Time series of Normalized Difference Vegetation Index (NDVI) derived from multiple satellite sensors are crucial data to study vegetation dynamics. The Land Long Term Data Record Version 4 (LTDR V4) NDVI dataset was recently released at a 0.05 × 0.05° spatial resolution and daily temporal resolution. In this study, annual NDVI time series that are composited by the LTDR V4 and Moderate Resolution Imaging Spectroradiometer (MODIS) NDVI datasets (MOD13C1) are compared and evaluated for the period from 2001 to 2014 in China. The spatial patterns of the NDVI generally match between the LTDR V4 and MOD13C1 datasets. The transitional zone between high and low NDVI values generally matches the boundary of semi-arid and sub-humid regions. A significant and high coefficient of determination is found between the two datasets according to a pixel-based correlation analysis. The spatially averaged NDVI of LTDR V4 is characterized by a much weaker positive regression slope relative to that of the spatially averaged NDVI of the MOD13C1 dataset because of changes in NOAA AVHRR sensors between 2005 and 2006. The measured NDVI values of LTDR V4 were always higher than that of MOD13C1 in western China due to the relatively lower atmospheric water vapor content in western China, and opposite observation appeared in eastern China. In total, 18.54% of the LTDR V4 NDVI pixels exhibit significant trends, whereas 35.79% of the MOD13C1 NDVI pixels show significant trends. Good agreement is observed between the significant trends of the two datasets in the Northeast Plain, Bohai Economic Rim, Loess Plateau, and Yangtze River Delta. By contrast, the datasets contrasted in northwestern desert regions and southern China. A trend analysis of the regression slope values according to the vegetation type shows good agreement between the LTDR V4 and MOD13C1 datasets. This study demonstrates the spatial and temporal consistencies and discrepancies between the AVHRR LTDR and MODIS MOD13C1 NDVI products in China, which could provide useful information for the choice of NDVI products in subsequent studies of vegetation dynamics.
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Grassland, as one of the most important ecosystems on Earth, experiences fires that affect the local ecology, economy and society. Notably, grassland fires occur frequently each year in northeastern China. Fire occurrence is a complex problem with multiple causes, such as natural factors, human activities and land use. This paper investigates the disruptive effects of grassland fire in the northeastern Inner Mongolia Autonomous Region of China. In this study, we relied on thermal anomaly detection from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor to identify fire occurrences, and land use data were acquired by Landsat Thematic Mapper/Enhanced Thematic Mapper (TM/ETM). We discussed the relationship between land use and the spatial distribution of grassland fires. The results showed that the impact of land use on grassland fires was significant. Spatially, approximately 80% of grassland fires were clustered within 10 km of cultivated land, and grassland fires generally occurred in areas of intense human activity. The correlation between the spatial distribution of grassland fires and the land use degree in 2000, 2005 and 2010 was high, with R² values of 0.686, 0.716, 0.633, respectively (p < 0.01). These results highlight the importance of the relationship between land use and grassland fire occurrence in the northeastern Inner Mongolia Autonomous Region. This study provides significance for local fire management and prevention.
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Grassland fire is one of the most important disturbance factors of the natural ecosystem. Climate factors influence the occurrence and development of grassland fire. An analysis of the climate conditions of fire occurrence can form the basis for a study of the temporal and spatial variability of grassland fire. The purpose of this paper is to study the effects of monthly time scale climate factors on the occurrence of grassland fire in HulunBuir, located in the northeast of the Inner Mongolia Autonomous Region in China. Based on the logistic regression method, we used the moderate-resolution imaging spectroradiometer (MODIS) active fire data products named thermal anomalies/fire daily L3 Global 1km (MOD14A1 (Terra) and MYD14A1 (Aqua)) and associated climate data for HulunBuir from 2000 to 2010, and established the model of grassland fire climate index. The results showed that monthly maximum temperature, monthly sunshine hours and monthly average wind speed were all positively correlated with the fire climate index; monthly precipitation, monthly average temperature, monthly average relative humidity, monthly minimum relative humidity and the number of days with monthly precipitation greater than or equal to 5 mm were all negatively correlated with the fire climate index. We used the active fire data from 2011 to 2014 to validate the fire climate index during this time period, and the validation result was good (Pearson's correlation coefficient was 0.578), which showed that the fire climate index model was suitable for analyzing the occurrence of grassland fire in HulunBuir. Analyses were conducted on the temporal and spatial distribution of the fire climate index from January to December in the years 2011-2014; it could be seen that from March to May and from September to October, the fire climate index was higher, and that the fire climate index of the other months is relatively low. The zones with higher fire climate index are mainly distributed in Xin Barag Youqi, Xin Barag Zuoqi, Zalantun Shi, Oroqen Zizhiqi, and Molidawa Zizhiqi; the zones with medium fire climate index are mainly distributed in Chen Barag Qi, Ewenkizu Zizhiqi, Manzhouli Shi, and Arun Qi; and the zones with lower fire climate index are mainly distributed in Genhe Shi, Ergun city, Yakeshi Shi, and Hailar Shi. The results of this study will contribute to the quantitative assessment and management of early warning and forecasting for mid-to long-term grassland fire risk in HulunBuir.
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To fully understand the chemical diversity of an herbal medicine is challenging. In this work, we describe a new approach to globally profile and discover novel compounds from an herbal extract using multiple neutral loss/precursor ion scanning combined with substructure recognition and statistical analysis. Turmeric (the rhizomes of Curcuma longa L.) was used as an example. This approach consists of three steps: (i) multiple neutral loss/precursor ion scanning to obtain substructure information; (ii) targeted identification of new compounds by extracted ion current and substructure recognition; and (iii) untargeted identification using total ion current and multivariate statistical analysis to discover novel structures. Using this approach, 846 terpecurcumins (terpene-conjugated curcuminoids) were discovered from turmeric, including a number of potentially novel compounds. Furthermore, two unprecedented compounds (terpecurcumins X and Y) were purified, and their structures were identified by NMR spectroscopy. This study extended the application of mass spectrometry to global profiling of natural products in herbal medicines and could help chemists to rapidly discover novel compounds from a complex matrix.
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Curcuma/química , Curcumina/química , Terpenos/química , Cromatografia Líquida de Alta Pressão , Curcumina/análogos & derivados , Curcumina/isolamento & purificação , Interpretação Estatística de Dados , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura MolecularRESUMO
Because of less functionally critical carbohydrate sectors that contributed to the stability, efforts have been made to quantify intact recombinant human erythropoietin. A simple, rapid capillary electrophoresis with laser-induced fluorescence method for the assay of recombinant human erythropoietin was developed, with a limit of detection of intact recombinant human erythropoietin at subnanomolar concentration (up to 10 ng/mL or 3 × 10(-10) M), which is among the lowest reported. High sensitivity was accomplished by precolumn derivatization with the noncovalent dye NanoOrange. Capillary electrophoresis separation and reaction conditions were carefully manipulated for avoiding microheterogeneity of glycoforms and inhomogeneity of multiple labeling products. The fluorescence signal was linear over the range of 10 ng/mL-10 µg/mL, corresponding to the detection requirement of recombinant human erythropoietin in biofluids and pharmaceutical samples, as demonstrated by a real sample analysis. Although the salt in reaction mixtures showed a detrimental effect on the fluorescence of the derivatives, this method could tolerate a certain amount of salt, extending its application in biofluid analysis. In addition, zero-order fluorescence emission kinetics was obtained, indicating that the rapid decay of recombinant human erythropoietin was derived from a self-quenching effect.
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Eletroforese Capilar , Eritropoetina/análise , Proteínas Recombinantes/análise , Eritropoetina/sangue , Eritropoetina/urina , Fluorescência , Humanos , Lasers , Compostos Orgânicos/química , Reprodutibilidade dos Testes , Sais/química , Sensibilidade e Especificidade , Espectrometria de FluorescênciaRESUMO
Despite their crucial role in determining the fate of seeds, the type and breaking mode of seed dormancy in peatland plants in temperate Asia with a continental monsoon climate are rarely known. Fifteen common peatland plant species were used to test their seed germination response to various dormancy-breaking treatments, including dry storage (D), gibberellin acid soaking (GA), cold stratification (CS), warm followed cold stratification (WCS), GA soaking + cold stratification (GA + CS) and GA soaking + warm followed cold stratification (GA + WCS). Germination experiment, viability and imbibition test, and morphological observation of embryos were conducted. Of the 15 species, nine showed physiological dormancy (PD), with non-deep PD being the dominant type. Four species, Angelica pubescens, Cicuta virosa, Iris laevigata, and Iris setosa exhibited morphophysiological dormancy. Two species, Lycopus uniflorus and Spiraea salicifolia, demonstrated nondormancy. Overall, the effect hierarchy of dormancy-breaking is: CS > GA > WCS > GA + CS > D > GA + WCS. Principal component analysis demonstrated that seed traits, including embryo length: seed length ratio, seed size, and monocot/eudicot divergence, are more likely to influence seed dormancy than environmental factors. Our study suggests that nearly 90% of the tested peatland plant species in the Changbai Mountains demonstrated seed dormancy, and seed traits (e.g. embryo-to-seed ratio and seed size) and abiotic environmental factors (e.g. pH and temperature seasonality) are related to germination behavior, suggesting seed dormancy being a common adaptation strategy for the peatland plants in the temperate montane environment.
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Objective To observe the expression of adhesion molecule CD226 on the small intestinal group 3 innate lymphoid cells (ILC3) in mice. Methods The bioinformatics was used to analyze the expression of CD226 on murine ILCs. Small intestinal mucosal lamina propria lymphocytes (LPL) were isolated from wild-type C57BL/6J mice, and the expression of CD226 on ILC1 and ILC3 was detected by flow cytometry. A mouse model of dextran sulfate sodium (DSS)-induced colitis was constructed to observe the changes in the expression of CD226 on ILC3. Results Both ILC1 and ILC3 in the mice small intestine expressed CD226 molecules; the proportion of ILC3 was reduced, while the expression level of CD226 on ILC3 was increased in the colitis model. Conclusion CD226 is expressed on the small intestines of mice, and although the proportion of ILC3 decreases in the DSS-induced colitis, the expression of CD226 on ILC3 increases.
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Colite , Imunidade Inata , Animais , Camundongos , Colite/induzido quimicamente , Intestino Delgado , Linfócitos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: The enrichment of peri-cancerous adipose tissue is a distinctive feature of colorectal cancer (CRC), accelerating disease progression and worsening prognosis. The communication between tumor cells and adjacent adipocytes plays a crucial role in CRC advancement. However, the precise regulatory mechanisms are largely unknown. This study aims to explore the mechanism of migration and invasion inhibitory protein (MIIP) downregulation in the remodeling of tumor cell-adipocyte communication and its role in promoting CRC. RESULTS: MIIP expression was found to be decreased in CRC tissues and closely associated with adjacent adipocyte browning. In an in vitro co-culture model, adipocytes treated with MIIP-downregulated tumor supernatant exhibited aggravated browning and lipolysis. This finding was further confirmed in subcutaneously allografted mice co-injected with adipocytes and MIIP-downregulated murine CRC cells. Mechanistically, MIIP interacted with the critical lipid mobilization factor AZGP1 and regulated AZGP1's glycosylation status by interfering with its association with STT3A. MIIP downregulation promoted N-glycosylation and over-secretion of AZGP1 in tumor cells. Subsequently, AZGP1 induced adipocyte browning and lipolysis through the cAMP-PKA pathway, releasing free fatty acids (FFAs) into the microenvironment. These FFAs served as the primary energy source, promoting CRC cell proliferation, invasion, and apoptosis resistance, accompanied by metabolic reprogramming. In a tumor-bearing mouse model, inhibition of ß-adrenergic receptor or FFA uptake, combined with oxaliplatin, significantly improved therapeutic efficacy in CRC with abnormal MIIP expression. CONCLUSIONS: Our data demonstrate that MIIP plays a regulatory role in the communication between CRC and neighboring adipose tissue by regulating AZGP1 N-glycosylation and secretion. MIIP reduction leads to AZGP1 oversecretion, resulting in adipose browning-induced CRC rapid progression and poor prognosis. Inhibition of ß-adrenergic receptor or FFA uptake, combined with oxaliplatin, may represent a promising therapeutic strategy for CRC with aberrant MIIP expression.
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The impact of snowmelt on surface hydrothermal conditions is a research hot spot given the background of global warming. However, existing remote sensing-based studies have mostly focused on demonstrating the impacts of snow and are based on large time scales. How to measure the duration of snowmelt impact on surface hydrothermal conditions more accurately is a problem that needs to be addressed. We used a method to quantify the impact duration of snowmelt based on the characteristics of the phase change in land surface temperature (LST) and land surface water index (LSWI) after melting. We analyzed the snow factors that have caused the difference in impact duration and the interaction on the impact duration. The results are described as follows: (1) The LST and LSWI changes after snow melting are characterized by distinct phases. (2) The duration of the snowmelt impact on LST ranged from 4.61 days in the south to 21.23 days in the north; the effect of snow on the LSWI ranged from 8.06 days in the south to 25.38 days in the north. (3) The two durations have a significant positive correlation with snow depth and snow melt date. The combination of several snow parameters and other meteorological factors has a significant interaction effect on the duration of snowmelt influence. In most combinations where there is no interaction, the duration is significantly affected only by snow elements. The interaction can change the direction and extent of the effect of a single snow or meteorological element on the duration of snow impact. This research can supplement the theoretical basis for solving ecological problems and production in the study area, such as spring drought, forage mowing, and cold protection of livestock.
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Global climate change has led to significant changes in land surface phenology. At present, research on the factors influencing the start of the growing season (SOS) mainly focuses on single factor effects, such as temperature and precipitation, ignoring the combined action of multiple factors. The impact of multiple factors on the spatial and temporal patterns of the SOS in the Northern Hemisphere is not clear, and it is necessary to combine multiple factors to quantify the degrees of influence of different factors on the SOS. Based on the GIMMS3g NDVI dataset, CRU climate data and other factor data, we used geographic detector model, random forest regression model, multiple linear regression, partial correlation analysis and Sen + Mann-Kendall trend analysis to explore the variation of the SOS in the Northern Hemisphere to reveal the main driving factors and impact threshold of 17 influencing factors on the SOS. The results showed that (1) during the past 34 years (1982-2015), the SOS in Europe and Asia mainly showed an advancing trend, whereas the SOS in North America mainly showed a delaying trend. (2) The SOS was mainly controlled by frost frequency, temperature and humidity. Increasing frost frequency inhibited the advancement of the SOS, and increasing temperature and humidity promoted the advancement of the SOS. (3) There were thresholds for the influences of the driving factors on the SOS. Outside the threshold ranges, the response mechanism of the SOS to driving factors changed. The results are important for understanding the response of the SOS to global climate change.
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BACKGROUND: Migraine is commonly seen as a cyclic disorder with variable cortical excitability at different phases. Herein, we investigated the cortical excitability in migraine without aura patients during an attack (MWoA-DA) and interictal period (MWoA-DI) and further explored the functional connectivity (FC) in brain regions with cortical excitability abnormalities in patients. METHODS: Seven MWoA-DA patients, twenty-seven MWoA-DI patients, and twenty-nine healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scan. The amplitude of low-frequency fluctuations (ALFF) was assessed to identify spontaneous brain activity. Then, brain regions showing significant differences across groups were identified as regions of interest (ROI) in FC analysis. RESULTS: Compared with MWoA-DI patients and HC, the ALFF in the trigeminocervical complex (TCC) was higher in the MWoA-DA patients. Decreased FC in MWoA-DA patients was found between TCC and left postcentral gyrus compared with MWoA-DI patients. Compared with HC, ALFF was lower in the right cuneus but higher in the right rolandic operculum of MWoA-DI patients. Additionally, the ALFF in the right cuneus was negatively correlated with the Migraine Disability Assessment Scale (MIDAS) in MWoA-DI patients. CONCLUSIONS: The trigeminovascular system and impairments in descending pain modulatory pathways participate in the pathophysiology of migraine during the ictal period. The defense effect exists in the interictal phase, and the dysfunction in the cuneus may be related to the disease severity. This dynamic change in different brain regions could deepen our understanding of the physiopathology underlying migraine.