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Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.
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A model of the Li-diffused inactive layer in P-type high purity germanium detectors is built to describe the transportation of charge carriers and calculate the charge collection efficiency therein. The model is applied to calculate charge collection efficiency of a P-type point-contact germanium detector used in rare event physics experiments and validated in another P-type semi-planar germanium detector. The calculated charge collection efficiency curves are well consistent with measurements for both detectors. Effects of the Li doping processes on the charge collection efficiency are discussed based on the model. This model can be easily extended to other P-type germanium detectors, for instance, the P-type broad-energy Ge detector, and the P-type inverted-coaxial point-contact detector.
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Identification of prognosis-related risk factors and accurate assessment of risk stratification in patients with gastrointestinal stromal tumor (GIST) is of great significance not only for establishing a reliable prognostic model and developing a follow-up plan but also for selecting potential populations benefiting from neoadjuvant therapies. Although several risk stratification models have been established, it is still challenging to accurately assess patients' risk of recurrence, and the performance of these prediction models still needs to be improved. This review focused on the latest studies in recurrence risk assessment for GIST patients, and summarized potential predictive markers and recurrence risk models related to tumor-related characteristic parameters, novel laboratory examinations, radiological imaging signatures and molecular pathological features, which could provide a reference for accurate risk stratification and individualized targeted therapies for GIST patients.
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Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/cirurgia , Medição de Risco , Prognóstico , Fatores de Risco , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.
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Eletricidade , ElétronsRESUMO
Objective: To investigate the functional outcomes and postoperative complications of Cheng's GIRAFFE reconstruction after proximal gastrectomy. Methods: A descriptive case series study was conducted. Clinical data of 100 patients with adenocarcinoma of the esophagogastric junction who underwent Cheng's GIRAFFE reconstruction after proximal gastrectomy in Cancer Hospital of University of Chinese Academy of Sciences (64 cases), Zhejiang Provincial Hospital of Chinese Medicine (24 cases), Lishui Central Hospital (10 cases), Huzhou Central Hospital (1 case) and Ningbo Lihuili Hospital (1 case) from September 2017 to June 2021 were retrospectively analyzed. Of 100 patients, 64 were males and 36 were females; the mean age was (61.3 ± 11.1) years and the BMI was (22.7±11.1) kg/m(2). For TNM stage, 68 patients were stage IA, 24 were stage IIA and 8 were stage IIB. Postoperative functional results and postoperative complications of radical gastrectomy with Giraffe reconstruction were analyzed and summarized. Gastroesophageal reflux disease questionnaire (RDQ) score and postoperative endoscopy were used to evaluate the occurrence of reflux esophagitis and its grade (grade N, grade A, grade B, grade C, and grade D from mild to severe reflux). The continuous data conforming to normal distribution were expressed as (mean ± standard deviation), and those with skewed distribution were presented as median (Q1, Q3). Results: All the 100 patients successfully completed R0 resection, including 77 patients undergoing laparoscopic surgery and 23 patients undergoing laparotomy. The Giraffe anastomosis time was (38.6±14.0) min; the blood loss was (73.0±18.4) ml; the postoperative hospital stay was 9.5 (8.2, 13.0) d; the hospitalization cost was (6.0±0.3) ten thousand yuan. Fourteen cases developed perioperative complications (14.0%), including 7 cases of pleural effusion or pneumonia, 3 cases of anastomotic leakage, 2 cases of gastric emptying disorder, 1 case of gastrointestinal hemorrhage and 1 case of anastomotic stenosis, who were all improved and discharged after symptomatic management. Patients were followed up for (33.3±1.6) months. Eight patients were found to have reflux symptoms by RDQ scale six months after surgery, and 11 patients (11/100,11.0%) were found to have reflux esophagitis by gastroscopy, including 6 in grade A, 3 in grade B, and 2 in grade C. All the patients could control their reflux symptoms with behavioral guidance or oral PPIs. Conclusion: Cheng's GIRAFFE reconstruction has good anti-reflux efficacy and gastric emptying function; it can be one of the choices of reconstruction methods after proximal gastrectomy.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Junção Esofagogástrica , Gastrectomia , Procedimentos de Cirurgia Plástica , Neoplasias Gástricas , Adenocarcinoma/cirurgia , Idoso , Neoplasias Esofágicas/cirurgia , Esofagite Péptica/etiologia , Junção Esofagogástrica/cirurgia , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Refluxo Gastroesofágico/etiologia , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Neoplasias Gástricas/cirurgiaRESUMO
Objective: To analyze the thyroid condition and influencing factors of radiation workers, and to provide scientific basis for radiation protection management. Methods: In April 2020, 4308 radiation workers from October 1, 2017 to September 30, 2019 were collected for occupational health examination in Hangzhou Occupational Disease Prevention and Treatment Hospital, the data included basic information, Thyroid hormone level and thyroid color doppler ultrasound results. The thyroid status of radiation workers in different subgroups was compared. The influencing factors of Thyroid nodule were analyzed by multiple logistic regression. Results: 616 radiation workers had abnormal thyroid gland (14.3%, 616/4308) . The main manifestations of thyroid gland abnormality were abnormal Thyroid nodule (5.1%, 220/4308) and abnormal TSH level (7.1%, 308/4308) . Compared with the male radiation workers, the abnormal rate of Thyroid nodule, T3 and Tsh in female radiation workers was higher (P<0.05) , and the abnormal rate of Thyroid nodule, T3 and T4 increased with the increase of working age (P<0.05) . Radiation Workers in non-rated medical institutions and private medical institutions had the highest detection rate of Thyroid nodule (P<0.05) , and there was no significant difference in thyroid abnormalities among Workers (P<0.05) . By multiple logistic regression analysis, Sex (female) , age and institution type (private) were all independent risk factors for Thyroid nodule (95% CI: 1.548~2.763ã1.002~1.030, P<0.05) . Conclusion: Ionizing radiation can cause thyroid damage in radiation workers, so we should pay more attention to the radiation protection management of female, high age, private and district medical organizations, so as to protect the health of radiation workers.
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Doenças Profissionais , Exposição Ocupacional , Nódulo da Glândula Tireoide , Feminino , Humanos , Masculino , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Radiação Ionizante , Nódulo da Glândula Tireoide/epidemiologiaRESUMO
Objective: To investigate the safety and feasibility of proximal partial gastrectomy with Cheng's Giraffe esophagogastric reconstruction for the treatment of early Siewert II adenocarcinoma of esophagogastric junction (AEG). Methods: Indication of Cheng's Giraffe esophagogastric reconstruction: (1) Siewert II AEG or Siewert III AEG with diameter < 4 cm; (2) preoperative staging as cT1-2N0M0. A descriptive case series study was carried out. Clinical data of 34 patients with Siewert II AEG undergoing proximal partial gastrectomy and Cheng's Giraffe esophagogastric reconstruction at Department of Abdominal Surgery of Zhejiang Cancer Hospital and Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from February to July 2018 were retrospectively collected and analyzed, including 14 cases in IA stage, 11 cases in IIA stage and 8 cases in IIB stage. Brief procedure of Cheng's Giraffe esophagogastric reconstruction was as follows: Firstly, 12 cm long tubular stomach was formed by longitudinal incision 4 cm away from the great curvature of the stomach. Secondly, the gastric fundus and His angle were formed. Finally, the distance from His angle to esophagal-tubular gastric anastomosis should be more than 5 cm. The reflux disease questionare (RDQ) scores, radionuclide gastric emptying scintigraphy, and 24-hour multichannel intraluminal (MII)-pH monitoring technology were used to evaluate postoperative gastric emptying and gastroesophageal reflux. Result: All 34 patients successfully completed proximal partial gastrectomy with Cheng's Giraffe esophagogastric reconstruction, including 13 cases by open surgery and 21 cases by laparoscopic surgery. The operation time was (144.6±39.8) minutes, the blood loss during operation was (35.4±17.2) ml. No laparoscopic case was converted to open surgery and no postoperative complication was observed. The postoperative hospital stay was (8.4±2.5) days. The postoperative RDQ score was 4.4±3.1 one month after operation, and 3.3±2.5 six months after operation. Gastric-half emptying time was (67.0±21.5) minutes, and the residual ratio was (52.2±7.7)% in 1 hour, (36.4±3.1)% in 2 hours and (28.8±3.6)% in 3 hours at postoperative 1-month. The 24-hour MII-pH monitoring at postoperative 2-month revealed the frequency of acid reflux was (12.6±7.9) times, frequency of non-acid reflux was (19.6±9.7) times, DeMeester score was 5.8±2.9. Conclusion: Cheng's Giraffe esophagogastric reconstruction is safe and feasible in the treatment of Siewert type II AEG, and has good dynamic and anti-reflux effects.
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Adenocarcinoma/cirurgia , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/cirurgia , Gastrectomia , Procedimentos de Cirurgia Plástica/métodos , Neoplasias Gástricas/cirurgia , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIMS: Plant tissues are the reservoirs of beneficial and harmful microbes that regulates plant growth. In the present study, we investigated the diversity, function and colonization of sugarcane roots associated with Bacillus spp. METHODS AND RESULTS: A total of 20 Bacillus strains were isolated and identified by 16S rRNA gene sequencing, and their genetic diversity was examined by BOX, ERIC, REP, (GTG)5 PCR techniques. Among all Bacillus isolates, 65% showed indole acetic acid-like compounds production, 50% solubilized phosphorus and 25% of the isolates were able to secrete siderophore. Moreover, all 20 Bacillus isolates showed antifungal activity against eight fungal pathogens and 11 of them (55%) antagonized tomato grey mold. Based on the plant growth-promoting traits and antifungal potential, isolate Y8 was selected for root and plant tissue colonization assays and a greenhouse-level sugarcane growth promotion study. Fluorescence microscopy results confirmed that isolate Y8 has a strong ability to colonize in the sugarcane root and leaves, and the root surface association of Y8 was confirmed by scanning electron microscopy. Furthermore, greenhouse experimental results demonstrated that Y8 has a significant effect on enhancing sugarcane biomass and root length. CONCLUSIONS: Endophytic Bacillus strains have growth-promoting properties and anti-fungal ability that can enhance plant fitness in an eco-friendly manner. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic Bacillus strains would be a potential alternative to chemical fertilizer as well as a biocontrol agent in the future.
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Bacillus/isolamento & purificação , Bacillus/fisiologia , Saccharum/crescimento & desenvolvimento , Saccharum/microbiologia , Antifúngicos/metabolismo , Bacillus/genética , Bacillus/metabolismo , Endófitos/genética , Endófitos/isolamento & purificação , Endófitos/metabolismo , Endófitos/fisiologia , Fungos/classificação , Fungos/genética , Variação Genética , Ácidos Indolacéticos/metabolismo , Fósforo/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Sideróforos/metabolismoRESUMO
We present results on light weakly interacting massive particle (WIMP) searches with annual modulation (AM) analysis on data from a 1-kg mass p-type point-contact germanium detector of the CDEX-1B experiment at the China Jinping Underground Laboratory. Datasets with a total live time of 3.2 yr within a 4.2-yr span are analyzed with analysis threshold of 250 eVee. Limits on WIMP-nucleus (χ-N) spin-independent cross sections as function of WIMP mass (m_{χ}) at 90% confidence level (C.L.) are derived using the dark matter halo model. Within the context of the standard halo model, the 90% C.L. allowed regions implied by the DAMA/LIBRA and CoGeNT AM-based analysis are excluded at >99.99% and 98% C.L., respectively. These results correspond to the best sensitivity at m_{χ}<6 GeV/c^{2} among WIMP AM measurements to date.
RESUMO
We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (m_{χ}) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in m_{χ} are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σ_{χN}^{SI} at 90% confidence level are derived as 2×10^{-32}â¼7×10^{-35} cm^{2} for TI analysis at m_{χ}â¼50-180 MeV/c^{2}, and 3×10^{-32}â¼9×10^{-38} cm^{2} for AM analysis at m_{χ}â¼75 MeV/c^{2}-3.0 GeV/c^{2}.
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Objective: To investigate the health status of radiation workers in a city and provide evidence for the health management of radiation workers. Methods: To investigate the health status of radiation workers in a city and provide evidence for the health management of radiation workers. Results: The majority of radiation workers are engaged in diagnostic radiology, male is more than female. The abnormal rate of micronuclear (0.59) and chromosome aberration (0.47%) was highest in nuclear medicine workers. The abnormal rate of micronuclear and chromosome aberration was similar with interventional and diagnostic radiology. Expect for micronuclear (χ(2)=32.945, P<0.01) and chromosome aberration (χ(2)=75149.737, P<0.01) , other radiation sensitive indicators have no difference. The abnormal rate of thyroid function (18.8%) (χ(2)=12.084, P<0.01) , micronuclear (0.25) (χ(2)=57.359, P<0.01) , chromosome aberration (0.08%) (χ(2)=17.209, P<0.01) in group whose service length exceeding 20 years was higher than other service length groups. There is no statistical difference in other radiation sensitive indicators among different service length group. Conclusion: Long-term low doses of ionizing radiation could affect radiation worker's health, expecially radiation workers engaged in nuclear medicine and radiotherapy. We must pay attention to occupaitonal health care and management to ensure radiation worker's health.
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Saúde Ocupacional , Radiologia , Aberrações Cromossômicas , Cidades , Feminino , Humanos , Masculino , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Radiação IonizanteRESUMO
BACKGROUND AND AIMS: Mast cell activation interferes with the effects of allergen-specific immunotherapy (SIT). Galectin-1 (Gal-1) is capable of regulating immune cells' functions. This study tests the hypothesis that administration of Gal-1 promotes and prolongs the efficacy of SIT via suppressing mast cell activation. METHODS: An intestinal allergy mouse model was developed. The coadministration of SIT and Gal-1 on suppression of the allergic responses, prevention of mast cell activation, and generation of antigen-specific regulatory T cells (Treg) in the intestine was observed in sensitized mice. RESULTS: The coadministration of Gal-1 and SIT markedly suppressed the allergic responses in the mouse intestine vs the use of either SIT alone or Gal-1 alone. The Gal-1 binds to the IgE/FcÉRI complexes on the surface of mast cells to prevent mast cell activation during SIT. Gal-1 promoted the SIT-generated allergen-specific Tregs in the intestine of sensitized mice. Coadministration of Gal-1 and SIT significantly enhanced the efficacy of immunotherapy in suppressing allergic responses in the intestine, which lasted for at least for 12 months. CONCLUSIONS: Long-term effects of specific immunotherapy on intestinal allergy can be achieved with Gal-1/SIT therapy by inhibiting mast cell activation and facilitating Treg development.
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Alérgenos/imunologia , Galectina 1/administração & dosagem , Hipersensibilidade/imunologia , Imunoterapia , Intestinos/imunologia , Citocinas/metabolismo , Dessensibilização Imunológica , Humanos , Hipersensibilidade/metabolismo , Hipersensibilidade/patologia , Imunomodulação/efeitos dos fármacos , Imunoterapia/métodos , Mucosa Intestinal/metabolismo , Intestinos/patologia , Mastócitos/imunologia , Mastócitos/metabolismo , Imunoterapia Sublingual , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th2/imunologia , Células Th2/metabolismoRESUMO
BACKGROUND: The overproduction of IgE plays a critical role in the pathogenesis of allergy; the mechanism is unclear. Histone-acetyltransferase (HAT) activities are required in gene transcription of a large number of molecules in the immune system of the body. OBJECTIVES: This study tests a hypothesis that HAT Tat-interactive protein 60 (Tip60) plays an important role in the initiation of IgE-mediated allergy. METHODS: The effects of Tip60 on regulating IgE expression were assessed with B cells. An intestinal allergy mouse model was developed to assess the role of Tip60 in the induction of IgE-mediated allergic inflammation. RESULTS: High levels of Tip60 were observed in the peripheral B cells of patients with FA. Tat-interactive protein 60 (Tip60) was required in the expression of IgE and IgG1 in B cells by inducing the chromatin remolding at the gene locus, in which histone acetylation, signal transducer and activator of transcription 6 (STAT6), and nuclear factor-κB at the locus of Iε promoter were markedly increased. Blocking Tip60 significantly attenuated the allergic inflammation in the mouse intestinal mucosa. CONCLUSIONS: Tat-interactive protein 60 (Tip60) plays an important role in the induction of IgE in B cells. Blocking Tip60 inhibits the allergic inflammation in the intestine, suggesting Tip60 inhibitor may be a potential anti-allergy drug.
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Hipersensibilidade/genética , Hipersensibilidade/imunologia , Enteropatias/genética , Enteropatias/imunologia , Lisina Acetiltransferase 5/genética , Lisina Acetiltransferase 5/imunologia , Adulto , Animais , Modelos Animais de Doenças , Feminino , Histona Acetiltransferases , Humanos , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Intestinos/imunologia , Masculino , CamundongosRESUMO
The characteristics of the surface inactive layer of a 1-kg-mass p-type point-contact germanium detector were studied. The thickness of the inactive layer and its uniformity on the top and lateral surfaces were measured. A charge collection efficiency function was developed according to the Monte Carlo simulation to describe the charge collection capacity along the depth within this inactive layer. In the energy range below 18keV, the surface, bulk, and total spectra of 57Co, 133Ba, 137Cs, and 60Co from simulations based on the charge collection efficiency function were well consistent with those from experiments.
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BACKGROUND AND AIMS: The function of interleukin (IL)-10-producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease-activated receptor (PAR)-2 has immunoregulatory functions. This study aimed to elucidate the role of PAR2 in the suppression of IL-10 expression in peripheral B cells. METHODS: Peripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2-like protein 12 (Bcl2L12) and IL-10 in the B cells was analyzed. An AR mouse model was developed. RESULTS: We observed that the expression of IL-10 was lower in the peripheral B cells from patients with airway allergy. A negative correlation was identified between the expression of IL-10 and PAR2 in B cells. Activation of PAR2 of B cells increased the expression of Bcl2L12 and suppression of LPS-induced IL-10 expression, which were inhibited by knocking down the Bcl2L12 gene. Treating B cells from AR patients with Bcl2L12-shRNA-carrying liposomes reversed the capability of IL-10 expression and the immunosuppressive function. Administration of Bcl2L12 shRNA-carrying liposomes attenuated experimental AR in mice. CONCLUSIONS: Activation of PAR2 inhibits the expression of IL-10 in B cells, which can be reversed by treating B cells with Bcl2L12 shRNA-carrying liposomes. The data suggest that regulation of Bcl2L12 may be a novel approach in the treatment for AR.
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Linfócitos B/metabolismo , Interleucina-10/metabolismo , Proteínas Musculares/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Receptor PAR-2/fisiologia , Rinite Alérgica/metabolismo , Regulação para Cima , Animais , Linfócitos B/enzimologia , Humanos , Camundongos , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacologia , Rinite Alérgica/genéticaRESUMO
BACKGROUND: Allergens from dust mites play a critical role in the pathogenesis of airway allergy. The mechanism by which dust mite allergens induce allergic diseases is not fully understood yet. OBJECTIVE: This study tests a hypothesis that the eighth subtypes of Dermatophagoides farina allergen (Derf8) play an important role in the induction of airway allergy. METHODS: The protein of Derf8 was synthesized via molecular cloning approach. Dendritic cells (DC) were stimulated with Derf8 in the culture, and then, the expression of T cell immunoglobulin mucin domain 4 (TIM4) in dendritic cells (DC) was analysed. The role of Derf8 in the induction of airway allergy was evaluated with a mouse model. RESULTS: Exposure to Derf8 markedly induced the TIM4 expression in DCs by modulating the chromatin at the TIM4 promoter locus. Derf8 played a critical role in the expansion of the T helper 2 response in the mouse airway via inducing DCs to produce TIM4. Administration with Derf8-depleted dust mite extracts (DME) inhibited the allergic inflammation and induced regulatory T cells in mice with airway allergy. CONCLUSION: Derf8 plays an important role in the initiation of dust mite allergy. Vaccination with Derf8-deficient DME is more efficient to inhibit the dust mite allergic inflammation than using wild DME.
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Antígenos de Dermatophagoides/imunologia , Hiper-Reatividade Brônquica/genética , Hiper-Reatividade Brônquica/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Glutationa Transferase/metabolismo , Proteínas de Membrana/genética , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais , Hiper-Reatividade Brônquica/patologia , Hiper-Reatividade Brônquica/terapia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Loci Gênicos , Humanos , Imunoterapia , Proteínas de Membrana/metabolismo , Camundongos , Vacinas/imunologiaRESUMO
BACKGROUND AND AIMS: Mast cells are the major effector cells in allergic disorders and many other informatory disorders. The mechanism of mast cell stabilization is not fully understood. Cumulative reports indicate that vitamin D (VitD) contributes to the homeostasis in the body. This study tests a hypothesis that VitD is required in the maintenance of the stability of mast cells. METHODS: The stability of mast cell lines, HMC1 cells, RBL-2H3 cells, p815 cells, and mouse bone marrow-derived mast cells (BMMC) was tested in the presence or absence of VitD3. RESULTS: Mast cells activated automatically in a VitD-deficient environment. Exposure to calcitriol in the culture increased the expression of VitD receptor (VDR) in mast cells. VDR formed complexes with Lyn in mast cells to inhibit the binding of Lyn to the ß chain of FcεRI and MyD88, which decreased the phosphorylation of Syk, decreased the levels of MAPK and NF-κB. VDR bound to the promoter of TNF-α to decrease the acetylation of histone H3/H4, RNA polymerase II and OCT1 (a transcription factor of TNF-α) at the promoter locus and repressed the expression of TNF-α in mast cells. CONCLUSIONS: The data demonstrate that VitD is required to maintain the stability of mast cells. The deficiency of VitD results in mast cell activation.
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Mastócitos/fisiologia , Vitamina D/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imunoglobulina E/imunologia , Mediadores da Inflamação/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Knockout , Regiões Promotoras Genéticas , Ligação Proteica , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Vitamina D/farmacologia , Quinases da Família src/metabolismoRESUMO
BACKGROUND: The generation of the tolerogenic dendritic cells (DC) is not fully understood yet. Forkhead box protein-3 (Foxp3) is an important molecule in the immune tolerance. This study tests a hypothesis that DCs express Foxp3, which can be upregulated by Staphylococcal enterotoxin B (SEB). METHODS: The expression of Foxp3 by DCs was evaluated by real-time RT-PCR, Western blotting, flow cytometry, and chromatin immunoprecipitation assay. RESULTS: We observed that mice treated with SEB at 0.25-0.5 µg/mouse showed high frequencies of transforming growth factor (TGF)-ß-producing CD4+ T cells and TGF-ß-producing DCs in the intestine, while the IL-4+ CD4+ T cells and TIM4+ DCs were dominated in the intestine in mice treated with SEB at 1-10 µg/mouse. Treating DCs with SEB in the culture induced high levels of Foxp3 at the TGF-ß promoter locus. The function of Foxp3 was blocked by STAT6 (signal transducer and activator transcription-6); the latter was induced by exposing DCs to SEB in the culture at doses of 100-400 ng/ml. Treating allergic mice with specific immunotherapy (SIT) together with SEB significantly promoted the therapeutic effects on the allergic responses than treating with SIT alone. CONCLUSION: Dendritic cells have the capacity to express Foxp3, which can be upregulated by exposure to SEB.
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Células Dendríticas/imunologia , Fatores de Transcrição Forkhead/metabolismo , Hipersensibilidade/terapia , Tolerância Imunológica , Animais , Células Dendríticas/metabolismo , Enterotoxinas/farmacologia , Enterotoxinas/uso terapêutico , Fatores de Transcrição Forkhead/biossíntese , Imunoterapia , Interleucina-4/metabolismo , Camundongos , Fator de Transcrição STAT6/imunologia , Fator de Crescimento Transformador beta/metabolismo , Regulação para CimaRESUMO
Fe(3)O(4)@C microcapsules were prepared using carbon-coated α-FeOOH nanorods as precursors, which were synthesized via two-step hydrothermal reactions. During the subsequent sintering procedure, α-FeOOH was reduced to Fe(3)O(4) by carbon, accompanied by the formation of mesopores. In Fe(3)O(4)@C microcapsules, mesoporous Fe(3)O(4) nanorods are coated with amorphorous carbon layers. The Fe(3)O(4)/C composites with such special structures demonstrate high specific capacity and good cyclic stability as anode materials in Li test cells.
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Cristalização/métodos , Compostos Férricos/química , Lítio/química , Lítio/isolamento & purificação , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Nanotecnologia/métodos , Absorção , Cápsulas , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Porosidade , Propriedades de SuperfícieRESUMO
Tyrosine phosphorylation is controlled by a balance of tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Whereas the contribution of PTKs to breast tumorigenesis is the subject of intense scrutiny, the potential role of PTPs is poorly known. RPTPalpha is implicated in the activation of Src family kinases, and regulation of integrin signaling, cell adhesion, and growth factor responsiveness. To explore its potential contribution to human neoplasia, we surveyed RPTPalpha protein levels in primary human breast cancer. We found RPTPalpha levels to vary widely among tumors, with 29% of cases manifesting significant overexpression. High RPTPalpha protein levels correlated significantly with low tumor grade and positive estrogen receptor status. Expression of RPTPalpha in breast carcinoma cells led to growth inhibition, associated with increased accumulation in G0 and G1, and delayed tumor growth and metastasis. To our knowledge, this is the first example of a study correlating expression level of a specific bona fide PTP with neoplastic disease status in humans.