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Background: The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy. Methods: HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models. Results: Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534-2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290-1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149-2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380-2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005-2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236-2.263), higher BCLC stage (HR 1.516, 95% CI 1.300-1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198-2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060-1.997). Conclusion: Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients.
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Approximately 40% of patients with lung adenocarcinoma (LUAD) often develop bone metastases during the course of their disease. However, scarcely any in vivo model of LUAD bone metastasis has been established, leading to a poor understanding of the mechanisms underlying LUAD bone metastasis. Here, we established a multiorgan metastasis model via the left ventricular injection of luciferase-labeled LUAD cells into nude mice and then screened out lung metastasis (LuM) and bone metastasis (BoM) cell subpopulations. BoM cells exhibited greater stemness and epithelial-mesenchymal transition (EMT) plasticity than LuM cells and initially colonized the bone and subsequently disseminated to distant organs after being reinjected into mice. Moreover, a CD74-ROS1 fusion mutation (C6; R34) was detected in BoM cells but not in LuM cells. Mechanistically, BoM cells bearing the CD74-ROS1 fusion highly secrete the C-C motif chemokine ligand 5 (CCL5) protein by activating STAT3 signaling, recruiting macrophages in tumor microenvironment and strongly inducing M2 polarization of macrophages. BoM cell-activated macrophages produce a high level of TGF-ß1, thereby facilitating EMT and invasion of LUAD cells via TGF-ß/SMAD2/3 signaling. Targeting the CD74-ROS1/CCL5 axis with Crizotinib (a ROS1 inhibitor) and Maraviroc (a CCL5 receptor inhibitor) in vivo strongly impeded bone metastasis and secondary metastasis of BoM cells. Our findings reveal the critical role of the CD74-ROS1/STAT3/CCL5 axis in the interaction between LUAD bone metastasis cells and macrophages for controlling LUAD cell dissemination, highlighting the significance of the bone microenvironment in LUAD bone metastasis and multiorgan secondary metastasis, and suggesting that targeting CD74-ROS1 and CCL5 is a promising therapeutic strategy for LUAD bone metastasis.
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Adenocarcinoma de Pulmão , Neoplasias Ósseas , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares , Macrófagos , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Animais , Humanos , Camundongos , Neoplasias Ósseas/secundário , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/secundário , Adenocarcinoma de Pulmão/metabolismo , Transição Epitelial-Mesenquimal/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Antígenos de Diferenciação de Linfócitos B/metabolismo , Antígenos de Diferenciação de Linfócitos B/genética , Quimiocina CCL5/metabolismo , Quimiocina CCL5/genética , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Camundongos Nus , Linhagem Celular Tumoral , Microambiente Tumoral , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Transdução de SinaisRESUMO
Mammalian target of rapamycin (mTOR) kinase functions as a central regulator of cell growth and metabolism, and its complexes mTORC1 and mTORC2 phosphorylate distinct substrates. Dysregulation of mTOR signaling is commonly implicated in human diseases, including cancer. Despite three decades of active research in mTOR, much remains to be determined. Here, we demonstrate that prolyl 4-hydroxylase alpha-2 (P4HA2) binds directly to mTOR and hydroxylates one highly conserved proline 2341 (P2341) within a kinase domain of mTOR, thereby activating mTOR kinase and downstream effector proteins (e.g. S6K and AKT). Moreover, the hydroxylation of P2341 strengthens mTOR stability and allows mTOR to accurately recognize its substrates such as S6K and AKT. The growth of lung adenocarcinoma cells overexpressing mTORP2341A is significantly reduced when compared with that of cells overexpressing mTORWT. Interestingly, in vivo cell growth assays show that targeting P4HA2-mTOR significantly suppresses lung adenocarcinoma cell growth. In summary, our study reveals an undiscovered hydroxylation-regulatory mechanism by which P4HA2 directly activates mTOR kinase, providing insights for therapeutically targeting mTOR kinase-driven cancers.
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Adenocarcinoma de Pulmão , Proliferação de Células , Neoplasias Pulmonares , Serina-Treonina Quinases TOR , Humanos , Hidroxilação , Serina-Treonina Quinases TOR/metabolismo , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Animais , Camundongos , Linhagem Celular Tumoral , Transdução de Sinais , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Pró-Colágeno-Prolina Dioxigenase/genéticaRESUMO
INTRODUCTION: Long-term spaceflight composite stress (LSCS) can cause adverse effects on human systems, including the central nervous system, which could trigger anxiety and depression. AIMS: This study aimed to identify changes in hippocampus synaptic plasticity under LSCS. METHODS: The present study simulated the real long-term space station environment by conducting a 42-day experiment that involved simulating microgravity, isolation, noise, circadian rhythm disruptions, and low pressure. The mood and behavior of the rats were assessed by behavior test. Transmission electron microscopy and patch-clamp were used to detect the changes in synapse morphology and electrophysiology, and finally, the expression of NMDA receptor channel proteins was detected by western blotting. RESULTS: The results showed that significant weight loss, anxiety, and depressive behaviors in rats were observed after being exposed to LSCS environment for 42 days. The synaptic structure was severely damaged, manifested as an obvious decrease in postsynaptic density thickness and synaptic interface curvature (p < 0.05; p < 0.05, respectively). Meanwhile, LTP was significantly impaired (p < 0.0001), and currents in the NMDAR channel were also significantly reduced (p < 0.0001). Further analysis found that LSCS decreased the expression of two key subtype proteins on this channel. CONCLUSION: These results suggested that LSCS-induced depressive behaviors by impairing synaptic plasticity in rat hippocampus.
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Plasticidade Neuronal , Voo Espacial , Humanos , Ratos , Animais , Plasticidade Neuronal/fisiologia , Hipocampo , Sinapses , Receptores de N-Metil-D-Aspartato , Potenciação de Longa Duração/fisiologiaRESUMO
Guaiane-type sesquiterpenoids are a class of terpenoids with [5,7] ring-fused system as the basic skeletal structure composed of three isoprene units, which are substituted by 4,10-dimethyl-7-isopropyl. According to the difference in functional groups and degree of polymerization, they can be divided into simple guaiane-type sesquiterpenoids, sesquiterpene lactones, sesquiterpene dimers, and sesquiterpene trimers. Natural guaiane-type sesquiterpenoids are widely distributed in plants, fungi, and marine organisms, especially in families such as Compositae, Zingiberaceae, Thymelaeaceae, Lamiaceae, and Alismataceae. Guaiane-type sesquiterpenoids have good antibacterial, anti-inflammatory, anticancer, and neuroprotective effects. In this paper, the novel guaiane-type sesquiterpenoids isolated and identified in recent 10 years(2013-2022) and their biological activities were reviewed in order to provide refe-rences for the research and development of guaiane-type sesquiterpenoids.
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Asteraceae , Sesquiterpenos , Humanos , Estrutura Molecular , Sesquiterpenos de Guaiano , Asteraceae/químicaRESUMO
To investigate the effect of maize/soybean intercropping on rhizosphere soil microbial communities and phosphorus (P) bioavailability, we examined the changes of soil bioavailable P fractions and microbial community characteristics in the monoculture and intercropping systems based on high-throughput sequencing. The results showed that maize/soybean intercropping increased the contents of rhizosphere soil organic matter (SOM), available phosphorus (AP), microbial biomass phosphorus (MBP), and aboveground biomass. The increase of AP was mainly related to the increasing enzyme extracted phosphorus (Enzyme-P) and hydrochloric acid extracted phosphorus (HCl-P) contents. The dominant bacterial phyla under each treatment were Proteobacteria, Actinobacteria, Acidobacteria and Chloroflexi, while the dominant bacterial genera were Nocardioides, Solirubacter, Sphingomonas and Arthrobacter, with Proteobacteria and Sphingomonas having the highest relative abundance. The relative abundance of Proteobacteria and Sphingomonas in intercropping maize rhizosphere soil was significantly higher than that in monoculture, and that of Proteobacteria in intercropping soybean rhizosphere soil was significantly higher than monoculture. Soil properties and P fractions were closely related to the rhizosphere soil microbial composition. In all, maize/soybean intercropping could affect the rhizosphere soil P bioavailability by altering the structure of rhizosphere microbial communities.
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Microbiota , Solo , Solo/química , Zea mays , Glycine max , Rizosfera , Fósforo , Disponibilidade Biológica , Microbiologia do Solo , Bactérias/genética , ProteobactériasRESUMO
Bioretention facilities are one of the most widely used measures for urban stormwater control and utilization. In this study, the accumulation characteristics of polycyclic aromatic hydrocarbons (PAHs) in bioretention facilities and the effects of PAHs on the structure of microbial communities were explored by combining on-site monitoring and water distribution simulation experiments. The correlation between pollutant accumulation and dominant microorganisms in the bioretention systems was also clarified. The results showed that all 16 priority PAHs were detected in the bioretention facilities in the sponge city pilot area. The PAH concentrations in the soil during the non-rainy season were higher than those in the rainy season and medium- and high-ring PAHs dominated. PAHs in the study area were mainly derived from coal and biomass combustion. The potential carcinogenic risk of PAHs accumulated in the bioretention facilities in the study area was low. The microbial diversity during the non-rainy season was greater than that during the rainy season. Firmicutes, Bacteroidetes, Bacteroides, and Massilia were strongly correlated with naphthalene (NAP), pyrene (PYR), fluoranthene (FLT), and benzo[a]pyrene (BaP). According to the results of the small-scale water distribution test, the addition of PAHs had little effect on the decline in water quantity, and there was no significant regularity in the reduction of water quality including TP, NH4+-N, NO3-N, and TN. The addition of PAHs had a significant effect on the microbial community structure and an inhibitory effect on enzyme activity.
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Poluentes Ambientais , Microbiota , Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/análise , Carcinógenos/análise , Solo/química , Monitoramento Ambiental , China , Medição de RiscoRESUMO
In order to establish the standardized processing technology of the hot water washing of Euodiae Fructus, this study, based on the traditional processing method of hot water washing of Euodiae Fructus recorded in ancient works and modern processing specifications of traditional Chinese medicine decoction pieces, took the yield of decoction pieces and the content of main components as the indicators and optimized the processing conditions by orthogonal test based on the results of single factor investigation. At the same time, electronic tongue technology was used to analyze the change law of the taste index of Euodiae Fructus during the hot water washing. The results of the single factor investigation showed that the content of the main components in Euodiae Fructus showed some regular changes during the processing. Specifically, the content of chlorogenic acid, hyperin, isorhamnetin-3-O-rutinoside, isorhamnetin-3-O-galactoside, and dehydroevodiamine decreased significantly, with average decreases of-23.75%,-27.80%,-14.04%,-14.03%, and-13.11%, respectively. The content of limonin increased significantly with an average increase of 19.83%. The content of evodiamine, rutaecarpine, evocarpine, and dihydroevocarpine showed fluctuating changes and generally increased, with average variation amplitudes of 0.54%,-3.78%, 2.69%, and 5.13%, respectively. The orthogonal test results showed that the optimum processing parameters for the hot water washing of Euodiae Fructus were as follows: washing time of 2 min, the solid-to-liquid ratio of 1â¶10 g·mL~(-1), washing temperature of 80 â, washing once, and drying at 50 â. After the hot water washing processing, the average yield of Euodiae Fructus pieces was 94.80%. The content of limonin, evodiamine, and rutaecarpine was higher than those of raw pro-ducts, and the average transfer rates were 102.56%, 103.15%, and 105.16%, respectively. The content of dehydroevodiamine was lower than that of the raw products, and the average transfer rate was 83.04%. The results of taste analysis showed that the hot water washing could significantly reduce the salty, astringent, and bitter tastes of Euodiae Fructus. This study revealed the influence of the hot water washing on the content of main components and taste of Euodiae Fructus, and the processing technology of the hot water was-hing of Euodiae Fructus established in this study was stable, feasible, and suitable for industrial production, which laid a foundation for clarifying its processing principle and improving the quality standard and clinical application value of decoction pieces.
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Medicamentos de Ervas Chinesas , Limoninas , Paladar , Tecnologia , Cromatografia Líquida de Alta Pressão/métodosRESUMO
In recent years, the research on non-point source (NPS) pollution has been deepening, but it is focused on the large-scale watershed or region. There are a few studies on the scales of small watershed and runoff plot, and it is even less to analyze the characteristics and mechanism of non-point source pollution in certain watershed by combining three different scales. Based on the combination of natural rainfall monitoring and MIKE model simulation, the Shaanxi section of Hanjiang River Basin in China was taken as an example to study the characteristics of NPS pollution at different spatial scales. The results showed that there was an obvious correlation between rainfall and runoff/sediment yield. The order of runoff yield/sediment yield per unit area was as follows: woodland > forested and grassy land > arable land. There was a significant relationship between the loss of total phosphorus and the sediment yield in the runoff plots. The total nitrogen pollution was serious, with an average concentration of 3.8 mg/L. The nutrient loss was in the form of nitrate nitrogen, with an average proportion of 63.06%. For small watershed scale, the characteristics of rainfall runoff pollution generation were like runoff plot scale, both have obvious initial scour phenomenon. However, compared with runoff plot scale, the pollutant loss concentration increases with a strong lag. The MIKE model based on the coupling of hydrology, hydrodynamics, and pollution load had a strong applicability in the basin. The critical source areas of NPS pollution were identified, and five scenarios were laid out in the areas for the control of NPS pollution. Centralized livestock and poultry farming had the best reduction effect.
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Poluição Difusa , Monitoramento Ambiental/métodos , Rios , China , Fósforo/análise , Nitrogênio/análiseRESUMO
A tetradentate ligand, 1,1,2,2-tetrakis(4-(pyridin-4-yl)phenyl)ethene (TPPE), was adopted to construct a two-dimensional coordination polymer that incorporated valence tautomerism and luminescence, and the synergistic effect arising from energy transfer from TPPE to the semiquinone moieties was experimentally and theoretically uncovered.
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Background: Endoscopic biopsy is the pivotal procedure for the diagnosis of gastric cancer. In this study, we applied whole-slide images (WSIs) of endoscopic gastric biopsy specimens to develop an endoscopic gastric biopsy assistant system (EGBAS). Methods: The EGBAS was trained using 2373 WSIs expertly annotated and internally validated on 245 WSIs. A large-scale, multicenter test dataset of 2003 WSIs was used to externally evaluate EGBAS. Eight pathologists were compared with the EGBAS using a man-machine comparison test dataset. The fully manual performance of the pathologists was also compared with semi-manual performance using EGBAS assistance. Results: The average area under the curve of the EGBAS was 0·979 (0·958-0·990). For the diagnosis of all four categories, the overall accuracy of EGBAS was 86·95%, which was significantly higher than pathologists (P< 0·05). The EGBAS achieved a higher κ score (0·880, very good κ) than junior and senior pathologists (0·641 ± 0·088 and 0·729 ± 0·056). With EGBAS assistance, the overall accuracy (four-tier classification) of the pathologists increased from 66·49 ± 7·73% to 73·83 ± 5·73% (P< 0·05). The length of time for pathologists to manually complete the dataset was 461·44 ± 117·96 minutes; this time was reduced to 305·71 ± 82·43 minutes with EGBAS assistance (P = 0·00). Conclusions: The EGBAS is a promising system for improving the diagnosis ability and reducing the workload of pathologists.
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The syntheses of valence tautomeric compounds with multistep transitions using new redox-active ligands are the long-term goal of the field of bistable materials. The redox-active tetraoxolene ligand, 2,7-di-tert-butylpyrene-4,5,9,10-tetraone (pyreneQ-Q), is now developed to synthesize a pair of dinuclear compounds {[CoL2]2(pyreneSq-Sq)}[Co(CO)4]2·xCH2Cl2·2C6H5CH3 (1, x = 2, L = 1,10-phenanthroline, phen; 2, x = 1.5, L = 2,2'-bipyridine, bpy). Variable-temperature magnetic susceptibilities and single-crystal X-ray diffraction measurements indicate a partial one-step valence tautomeric transition for 1 and a rare two-step valence tautomeric transition for 2, respectively. DFT calculation results are consistent with the experimental data, revealing the correlation between thermodynamic parameters and the one-step/two-step valence tautomeric behaviors.
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BACKGROUND: Visceral leishmaniasis (VL) is a parasitic disease caused by Leishmania and transmitted by infected sand flies. VL has a low incidence in China, and its clinical presentation is complex and atypical. This disease is easily misdiagnosed and can become life-threatening within a short period of time. Therefore, early, rapid and accurate diagnosis and treatment of the disease are essential. CASE SUMMARY: A 25-year-old male patient presented with the clinical manifestations of irregular fever, hepatosplenomegaly, increased polyclonal globulin, and pancytopenia. The first bone marrow puncture biopsy did not provide a clear diagnosis. In order to relieve the pressure and discomfort of the organs caused by the enlarged spleen and to confirm the diagnosis, splenectomy was performed, and hemophagocytic syndrome was diagnosed by pathological examination of the spleen biopsy. Following bone marrow and spleen pathological re-diagnosis and metagenomic next-generation sequencing (mNGS) technology detection, the patient was finally diagnosed with VL. After treatment with liposomal amphotericin B, the body temperature quickly returned to normal and the hemocytes recovered gradually. Post-treatment re-examination of the bone marrow puncture and mNGS data showed that Leishmania was not detected. CONCLUSION: As a fast and accurate detection method, mNGS can diagnose and evaluate the efficacy of treatment in suspicious cases of leishmaniasis.
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BACKGROUND: Rodents are widely distributed and are the natural reservoirs of a diverse group of zoonotic viruses. Thus, analyzing the viral diversity harbored by rodents could assist efforts to predict and reduce the risk of future emergence of zoonotic viral diseases. Rodents are commonly used in animal testing, particularly mice and rats. Experimental rats are important animal models, and a history of pathogenic infections in these animals will directly affect the animal trial results. The pathogenicity of Anellovirus (AV) remains poorly understood due to the lack of a suitable model cell line or animal to support the viral cycle. This study aimed to discover possible anelloviruses from the virome in feces of experimental rats by viral metagenomic technique. METHODS: Fecal samples were collected from 10 commercial SD rats and pooled into a sample pool and then subjected to libraries construction which was then sequenced on Illumina MiSeq platform. The sequenced reads were analyzed using viral metagenomic analysis pipeline and two novel anelloviruses (AVs) were identified from fecal sample of experimental rats. The prevalence of these two viruses was investigated by conventional PCR. RESULTS: The complete genomic sequence of these two AVs were determined and fully characterized, with strain name ratane153-zj1 and ratane153-zj2. The circular genomes of ratane153-zj1 and ratane153-zj2 are 2785 nt and 1930 nt in length, respectively, and both include three ORFs. Ratane153-zj1 closely clustered with members within the genus Wawtorquevirus and formed a separate branch based on the phylogenetic tree constructed over the amino acid sequence of ORF1 of the two AVs identified in this study and other related AVs. While the complete amino acid sequences of ORF1 of ratane153-zj2 (nt 335 to 1390) had the highest sequence identity with an unclassified AV (GenBank No. ATY37438) from Chinchilla lanigera, and they clustered with one AV (GenBank No. QYD02305) belonging to the genus Etatorquevirus from Lynx rufus. Conventional PCR with two sets of specific primers designed based on the two genomes, respectively, showed that they were detectable at a low frequency in cohorts of experimental rats. CONCLUSION: Our study expanded the genome diversity of AVs and provided genetic background information of viruses existed in experimental rats.
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Anelloviridae , Animais , Fezes , Genoma Viral , Metagenômica/métodos , Camundongos , Filogenia , Ratos , Ratos Sprague-DawleyRESUMO
N6-methyladenosine (m6A) methylation has been reported to play a role in type 2 diabetes (T2D). However, the key component of m6A methylation has not been well explored in T2D. This study investigates the biological role and the underlying mechanism of m6A methylation genes in T2D. The Gene Expression Omnibus (GEO) database combined with the m6A methylation and transcriptome data of T2D patients were used to identify m6A methylation differentially expressed genes (mMDEGs). Ingenuity pathway analysis (IPA) was used to predict T2D-related differentially expressed genes (DEGs). Gene ontology (GO) term enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to determine the biological functions of mMDEGs. Gene set enrichment analysis (GSEA) was performed to further confirm the functional enrichment of mMDEGs and determine candidate hub genes. The least absolute shrinkage and selection operator (LASSO) regression analysis was carried out to screen for the best predictors of T2D, and RT-PCR and Western blot were used to verify the expression of the predictors. A total of 194 overlapping mMDEGs were detected. GO, KEGG, and GSEA analysis showed that mMDEGs were enriched in T2D and insulin signaling pathways, where the insulin gene (INS), the type 2 membranal glycoprotein gene (MAFA), and hexokinase 2 (HK2) gene were found. The LASSO regression analysis of candidate hub genes showed that the INS gene could be invoked as a predictive hub gene for T2D. INS, MAFA,and HK2 genes participate in the T2D disease process, but INS can better predict the occurrence of T2D.
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OBJECTIVE: To investigate the effect of dasatinib on the expansion of NK cells in vitro, as well as the subsets, receptor expression and cytotoxic function of NK cells. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy adult volunteers and cultured with SCGM added IL-2 and IL-15 for expansion of NK cells. In this culture system, dasatinib of different concentrations were added. Cell counting and phenotyping by flow cytometry were used to evaluate the amplification efficiency of NK cells. FCM was used to detect the expression of receptors on the surface of NK cells and the distribution of subsets. Subsequently, degranulation assay and CFSE/7AAD based cytotoxicity assay were used to detect the effects of dasatinib on NK cytotoxicity against leukemia cell line K562 cells. RESULTS: The expansion efficiency of NK cells in vitro could be increased by dasatinib at the concentration range of 5-50 nmol/L, and the expansion efficiency of NK cells reached the peak at 20 nmol/L of dasatinib. The NK cytotoxicity against K562 cells in dasatinib cultured group at the concentration of 20 nmol/L was significantly higher than that in control group. For the cells cultured by disatinib in vitro, the MFI of CD226, NKP46 and NKG2D was up-regulated; the ratio of NKG2A+CD57- subset was down-regulated, while the ratio of NKG2A-CD57+ subset was up-regulated.The degranulation response of NKG2A-CD57+ NK cells to K562 cells was stronger than that of NKG2A+CD57- NK cells. CONCLUSION: The results shows that appropriate dose of dasatinib(20 nmol/L) can increases the amplification efficiency of NK cells, simultaneously up-regulates the expression of NK activating receptors and increases the NKG2A-CD57+ subset, which lead to the enhancement of NK cytotoxicty against leukemia cell lines.
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Antineoplásicos , Leucócitos Mononucleares , Adulto , Antineoplásicos/farmacologia , Dasatinibe/farmacologia , Humanos , Células K562 , Células Matadoras NaturaisRESUMO
The patient was a male who was found to be abnormal at the age of 4.5 months. He presented with irritability, motor regression and opisthotonus. Brain MRI revealed bilateral abnormality in the lentiform nucleus, thalamus, deutocerebrum and cerebellar hemispheres. Novel compound heterozygous mutations of SLC19A3 gene, c.950G>A(p.G317E) and c.962C>T(p.A321V), were found in the patient. Further study showed that c.950G>A was inherited from his father and c.962C>T came from his mother. Using bioinformatics software analysis, both of the mutations were found to be harmful. His symptoms were improved remarkably after biotin, thiamine and "cocktail" therapy. One month later a brain MRI revealed that the lesions in basal ganglia and cerebellar hemispheres were improved. The patient was definitely diagnosed with biotin-thiamine responsive basal ganglia disease (BTBGD). BTBGD is a treatable autosomal recessive disease and early administration of biotin and thiamine may lead to clinical improvement.
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Doenças dos Gânglios da Base , Choro , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Proteínas de Membrana Transportadoras , TiaminaAssuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Hipóxia/tratamento farmacológico , Panax/química , Proteínas/química , Ontologia Genética , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Simulação de Acoplamento Molecular , Proteínas/genética , Proteínas/metabolismoRESUMO
In the paper, hydrothermal carbon spheres (HTCs) are functionalized by the 3-aminobenzeneboronic acid (3-APBA) as a fluorescence sensor. The modification carbon spheres (3-APBA-HTCs) have shown excellent selectivity and sensitivity for efficient determination of L-tryptophan (L-Trp). The fluorescence sensor can selectively achieve the "On-Off" switchable functionality for L-Trp at an extremely low detection limit of 0.50 × 10- 5 mol/L.