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1.
Sensors (Basel) ; 23(4)2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36850944

RESUMEN

We examine a general wireless sensor network (WSN) model which incorporates a large number of sensors distributed over a large and complex geographical area. The study proposes solutions for a flexible deployment, low cost and high reliability in a wireless sensor network. To achieve these aims, we propose the application of an unmanned aerial vehicle (UAV) as a flying relay to receive and forward signals that employ nonorthogonal multiple access (NOMA) for a high spectral sharing efficiency. To obtain an optimal number of subclusters and optimal UAV positioning, we apply a sensor clustering method based on K-means unsupervised machine learning in combination with the gap statistic method. The study proposes an algorithm to optimize the trajectory of the UAV, i.e., the centroid-to-next-nearest-centroid (CNNC) path. Because a subcluster containing multiple sensors produces cochannel interference which affects the signal decoding performance at the UAV, we propose a diagonal matrix as a phase-shift framework at the UAV to separate and decode the messages received from the sensors. The study examines the outage probability performance of an individual WSN and provides results based on Monte Carlo simulations and analyses. The investigated results verified the benefits of the K-means algorithm in deploying the WSN.

2.
Interact Cardiovasc Thorac Surg ; 34(5): 775-782, 2022 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-35137083

RESUMEN

OBJECTIVES: Evaluation of smoke capture efficiency of different mobile smoke evacuation devices with respect to volatile organic compounds and their noise emission. METHODS: Electrosurgical incisions were performed on fresh porcine liver in an operating room with vertical laminar flow. The generated surgical smoke was analysed with proton-transfer-reaction mass spectrometry with and without the use of a mobile smoke evacuation system consisting of a smoke evacuator machine, a suction hose and a handpiece. The inlet of the mass spectrometer was positioned 40 cm above the specimen. Various devices were compared: a hard plastic funnel, a flexible foam funnel, an on-tip integrated aspirator of an electrosurgical knife and a standard secretion suction (Yankauer). Also, sound levels were measured at a distance of 40 cm from the handpieces' inlet. RESULTS: The smoke capture efficiency of the secretion suction was only 53%, while foam funnel, plastic funnel and integrated aspirator were all significantly more effective with a clearance of 95%, 91% and 91%, respectively. The mean sound levels were 68 and 59 A-weighted decibels with the plastic and foam funnel, respectively, 66 A-weighted decibels with the integrated aspirator and 63 A-weighted decibels with the secretion suction. CONCLUSIONS: Carcinogenic, mutagenic and reprotoxic volatile organic compounds in surgical smoke can be efficiently reduced by mobile smoke evacuation system, providing improved protection for medical personnel. Devices specifically designed for smoke evacuation are more efficient than standard suction tools. Noise exposure for the surgeon was lowest with the flexible foam funnel and higher with the other handpieces tested.


Asunto(s)
Exposición Profesional , Salud Laboral , Compuestos Orgánicos Volátiles , Animales , Electrocoagulación/métodos , Humanos , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Exposición Profesional/prevención & control , Quirófanos , Plásticos , Humo/efectos adversos , Humo/análisis , Humo/prevención & control , Porcinos , Compuestos Orgánicos Volátiles/análisis
3.
Surg Laparosc Endosc Percutan Tech ; 32(2): 172-175, 2021 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-34882614

RESUMEN

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) has become increasingly popular in the surgical treatment of thyroid cancer. However, its application in T3b disease has not been well-defined. METHODS: We conducted a quasi-experimental study on patients with an intraoperative diagnosis of T3bN0M0 differentiated thyroid carcinoma from January 2019 to January 2021 in our institution. Surgical and early oncological outcomes were assessed. RESULTS: Among 326 patients who underwent TOETVA for thyroid cancer, 12 cases had T3bN0M0 disease intraoperatively. The mean operation time was 136.67±7.32 minutes, with 7.17±0.83 mL of blood loss. No patients reported symptoms of postoperatively transient hypoparathyroidism, mental nerve, or recurrent laryngeal nerve injury. After radioactive iodine therapy, all patients had undetectable thyroglobulin, negative antithyroglobulin, and normal neck ultrasound. CONCLUSIONS: TOETVA seems to be a surgically and oncological safe method for differentiated thyroid cancer patients with small tumors invading strap muscle intraoperatively. The patients can be well-managed with endoscopic total thyroidectomy and postoperative radioactive iodine therapy. Further studies with a larger sample size and longer follow-up are needed to provide more solid evidence.


Asunto(s)
Cirugía Endoscópica por Orificios Naturales , Neoplasias de la Tiroides , Humanos , Radioisótopos de Yodo , Músculos/patología , Cirugía Endoscópica por Orificios Naturales/métodos , Estudios Retrospectivos , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos
4.
Artículo en Inglés | MEDLINE | ID: mdl-34874627

RESUMEN

In the past, the treatment of pectus carinatum has been managed by open, invasive surgical procedures, which involved the resection of cartilage growth plates (Ravitch procedure). By preventing normal bony growth and maturity, this technique often led to postoperative complications, such as acquired thoracic dystrophy, chronic pain and scarring, and stiffness of the whole anterior chest. Dyspnea and exercise intolerance due to restricted thoracic space and cardiac compression were not uncommon as well. Over the last 2 decades, nonsurgical and minimally invasive approaches have gained ground because it was recognized that simple sternal compression was able to remodel the elastic anterior chest wall and therefore correct pectus carinatum adequately/efficiently, at least in children. However, failure of this compressive brace treatment is not uncommon in adolescents and older patients. Abramson therefore developed a minimally invasive technique for the correction of pectus carinatum using a pectus bar that is placed anteriorly to the sternum. The procedure is less invasive and less risky than a pectus bar inserted for pectus excavatum, but the lateral fixation of the pectus bar in the Abramson procedure remains a challenge. We demonstrate the technical aspects of the procedure step by step including our solution for fixation of the stabilizers.


Asunto(s)
Tórax en Embudo , Pectus Carinatum , Adolescente , Niño , Tórax en Embudo/cirugía , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos , Pectus Carinatum/cirugía , Esternón/cirugía , Resultado del Tratamiento
5.
Ann Med Surg (Lond) ; 69: 102700, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34429956

RESUMEN

INTRODUCTION: Patients with Peutz-Jeghers syndrome (PJS) have high risk of malignancies, including gynecological cancers. Gastric type mucinous cervical adenocarcinoma might be presented in about 11-17% of PJS patients but the literature about this is limited. CASE PRESENTATION: We presented a rare case of a 39-year-old Vietnamese woman with Peutz-Jeghers syndrome who has gastric type adenocarcinoma (GAS) of the cervix. She underwent radical hysterectomy, and the diagnosis was confirmed on final pathology. CONCLUSIONS: Oncologists and pathologists should recognize this rare clinical scenario for early diagnosis and treatment. This subtype also has an aggressive nature and poor prognosis.

6.
Front Surg ; 8: 656249, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34250005

RESUMEN

Background: Surgical site infections (SSIs) are the most costly and second most frequent healthcare-associated infections in the Western world. They are responsible for higher postoperative mortality and morbidity rates and longer hospital stays. The aim of this study is to analyze which factors are associated with SSI in a modern general thoracic practice. Methods: Data were collected from our department's quality database. Consecutive patients operated between January 2014 and December 2018 were included in this retrospective study. Results: A total of 2430 procedures were included. SSIs were reported in 37 cases (1.5%). The majority of operations were video-assisted (64.6%). We observed a shift toward video-assisted thoracic surgery in the subgroup of anatomical resections during the study period (2014: 26.7%, 2018: 69.3%). The multivariate regression analysis showed that blood loss >100 ml (p = 0.029, HR 2.70) and open surgery (p = 0.032, HR 2.37) are independent risk factors for SSI. The latter was higher in open surgery than in video-assisted thoracic procedures (p < 0.001). In the subgroup of anatomical resection, we found the same correlation (p = 0.043). SSIs are also associated with significantly longer mean hospital stays (17.7 vs. 7.8 days, p < 0.001). Conclusion: As SSIs represent higher postoperative morbidity and costs, efforts should be made to maintain their rate as low as possible. In terms of prevention of SSIs, video-assisted thoracic surgery should be favored over open surgery whenever possible.

7.
Nature ; 591(7849): 306-311, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33627871

RESUMEN

Regulatory T cells (Treg cells) are essential for immune tolerance1, but also drive immunosuppression in the tumour microenvironment2. Therapeutic targeting of Treg cells in cancer will therefore require the identification of context-specific mechanisms that affect their function. Here we show that inhibiting lipid synthesis and metabolic signalling that are dependent on sterol-regulatory-element-binding proteins (SREBPs) in Treg cells unleashes effective antitumour immune responses without autoimmune toxicity. We find that the activity of SREBPs is upregulated in intratumoral Treg cells. Moreover, deletion of SREBP-cleavage-activating protein (SCAP)-a factor required for SREBP activity-in these cells inhibits tumour growth and boosts immunotherapy that is triggered by targeting the immune-checkpoint protein PD-1. These effects of SCAP deletion are associated with uncontrolled production of interferon-γ and impaired function of intratumoral Treg cells. Mechanistically, signalling through SCAP and SREBPs coordinates cellular programs for lipid synthesis and inhibitory receptor signalling in these cells. First, de novo fatty-acid synthesis mediated by fatty-acid synthase (FASN) contributes to functional maturation of Treg cells, and loss of FASN from Treg cells inhibits tumour growth. Second, Treg cells in tumours show enhanced expression of the PD-1 gene, through a process that depends on SREBP activity and signals via mevalonate metabolism to protein geranylgeranylation. Blocking PD-1 or SREBP signalling results in dysregulated activation of phosphatidylinositol-3-kinase in intratumoral Treg cells. Our findings show that metabolic reprogramming enforces the functional specialization of Treg cells in tumours, pointing to new ways of targeting these cells for cancer therapy.


Asunto(s)
Metabolismo de los Lípidos , Neoplasias/inmunología , Neoplasias/metabolismo , Transducción de Señal , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Animales , Colesterol/metabolismo , Ácido Graso Sintasas/metabolismo , Ácidos Grasos/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Ácido Mevalónico/metabolismo , Ratones , Fosfatidilinositol 3-Quinasa/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Proteínas de Unión a los Elementos Reguladores de Esteroles/antagonistas & inhibidores , Proteínas de Unión a los Elementos Reguladores de Esteroles/metabolismo , Linfocitos T Reguladores/enzimología , Regulación hacia Arriba
10.
Phys Rev Lett ; 125(23): 233602, 2020 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-33337189

RESUMEN

The Dicke model, which describes the coupling of an ensemble of spins to a harmonic oscillator, is known for its superradiant phase transition, which can both be observed in the ground state in a purely Hamiltonian setting, as well as in the steady state of an open-system Dicke model with dissipation. We demonstrate that, in addition, the dissipative Dicke model can undergo a second phase transition to a nonstationary phase, characterized by unlimited heating of the harmonic oscillator. Identifying the mechanism of the phase transition and deriving the scaling of the critical coupling with the system size we conclude that the novel phase transition can be understood as a cooperative breakdown of the oscillator blockade which otherwise prevents higher excitation of the system. We discuss an implementation with trapped ions and investigate the role of cooling, by which the breakdown can be suppressed.

11.
Nature ; 586(7830): 533-537, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33087915

RESUMEN

Practical and useful quantum information processing requires substantial improvements with respect to current systems, both in the error rates of basic operations and in scale. The fundamental qualities of individual trapped-ion1 qubits are promising for long-term systems2, but the optics involved in their precise control are a barrier to scaling3. Planar-fabricated optics integrated within ion-trap devices can make such systems simultaneously more robust and parallelizable, as suggested by previous work with single ions4. Here we use scalable optics co-fabricated with a surface-electrode ion trap to achieve high-fidelity multi-ion quantum logic gates, which are often the limiting elements in building up the precise, large-scale entanglement that is essential to quantum computation. Light is efficiently delivered to a trap chip in a cryogenic environment via direct fibre coupling on multiple channels, eliminating the need for beam alignment into vacuum systems and cryostats and lending robustness to vibrations and beam-pointing drifts. This allows us to perform ground-state laser cooling of ion motion and to implement gates generating two-ion entangled states with fidelities greater than 99.3(2) per cent. This work demonstrates hardware that reduces noise and drifts in sensitive quantum logic, and simultaneously offers a route to practical parallelization for high-fidelity quantum processors5. Similar devices may also find applications in atom- and ion-based quantum sensing and timekeeping6.

12.
Sci Adv ; 6(1): eaaw6443, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31911938

RESUMEN

Regulatory T cell (Treg) activation and expansion occur during neonatal life and inflammation to establish immunosuppression, yet the mechanisms governing these events are incompletely understood. We report that the transcriptional regulator c-Myc (Myc) controls immune homeostasis through regulation of Treg accumulation and functional activation. Myc activity is enriched in Tregs generated during neonatal life and responding to inflammation. Myc-deficient Tregs show defects in accumulation and ability to transition to an activated state. Consequently, loss of Myc in Tregs results in an early-onset autoimmune disorder accompanied by uncontrolled effector CD4+ and CD8+ T cell responses. Mechanistically, Myc regulates mitochondrial oxidative metabolism but is dispensable for fatty acid oxidation (FAO). Indeed, Treg-specific deletion of Cox10, which promotes oxidative phosphorylation, but not Cpt1a, the rate-limiting enzyme for FAO, results in impaired Treg function and maturation. Thus, Myc coordinates Treg accumulation, transitional activation, and metabolic programming to orchestrate immune homeostasis.


Asunto(s)
Ácidos Grasos/metabolismo , Terapia de Inmunosupresión , Inflamación/inmunología , Proteínas Proto-Oncogénicas c-myc/genética , Linfocitos T Reguladores/inmunología , Transferasas Alquil y Aril/inmunología , Animales , Animales Recién Nacidos/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Carnitina O-Palmitoiltransferasa/genética , Carnitina O-Palmitoiltransferasa/metabolismo , Citometría de Flujo , Homeostasis/inmunología , Inflamación/genética , Proteínas de la Membrana/inmunología , Ratones , Oxidación-Reducción , Fosforilación Oxidativa , Proteínas Proto-Oncogénicas c-myc/inmunología , Linfocitos T Reguladores/metabolismo
13.
Biomed Res Int ; 2019: 7391237, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31583246

RESUMEN

BACKGROUND: Obtaining tumor specimens and re-evaluating targeted markers is recommended, if possible, in breast cancer patients who relapsed after curative treatment. The biomarker status changes in rebiopsied tumors have been demonstrated to have considerable clinical implications. OBJECTIVES: To identify the changes of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status between the primary and recurrent lesions. MATERIALS AND METHODS: We conducted a study among 67 patients with recurrent breast cancer, recruited from January 2014 to September 2018 in the Vietnam National Cancer Hospital to compare ER, PR, and HER2 status between the primary and recurrent lesions. For each patient, a specimen of their primary tumor and another specimen of recurrent lesions underwent pathological assessment. Immunohistochemistry (IHC) was performed to determine ER, PR, and HER2 status in both specimens. RESULTS: Biomarker status conversion rates (in both directions) between primary and recurrent tumors were 26.9% for ER, 38.8% for PR, and 22.4% for HER2. Overall, IHC subtypes (hormone receptor positive, HER2 amplified, and triple-negative) changed in 25 out of 67 (37.3%) cases. Conversion rates were not statistically significantly different between patients with different recurrent sites and times of recurrence. Eight out of 13 initially triple-negative patients (61.5%) had a change to positive status of either ER, PR, or HER2. CONCLUSION: A substantial discordance in ER, PR, and HER2 status were observed between primary breast cancer tissues and recurrent lesions. Rebiopsy could bring new therapeutic opportunities in the management of patients with recurrent breast cancer.


Asunto(s)
Neoplasias de la Mama/genética , Receptor alfa de Estrógeno/genética , Receptor ErbB-2/genética , Receptores de Progesterona/genética , Neoplasias de la Mama Triple Negativas/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Biopsia , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Neoplasias de la Mama Triple Negativas/patología
14.
Cancer Control ; 26(1): 1073274819865269, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31364390

RESUMEN

INTRODUCTION: Albumin-bilirubin (ALBI) grade has been recently used in evaluation of liver function and prognosis of patients with hepatocellular carcinoma (HCC). However, in Vietnam, the utility of ALBI grade in clinical setting has not been adequately investigated. METHODS: This is a retrospective study of 110 patients with HCC treated with sorafenib from January 2010 to November 2018 at 2 tertiary hospitals in Vietnam. Prognostic value of ALBI grade was evaluated by Kaplan-Meier survival analysis and Cox proportional regression model. RESULTS: Results showed that the majority of ALBI grade 1 were Child-Pugh level A (97.5%); ALBI grade 2 was seen in all Child-Pugh score groups of 5, 6, 7, ≥8, whereas ALBI grade 3 was mostly reported in Child-Pugh score ≥8 group (83.3%). Compared with ALBI grade 3, ALBI grade 1 reduced 66.4% risk of death (hazards ratio [HR] = 0.336, 95% confidence interval [CI]: 0.115-0.981; P = .046). Compared with ALBI grade 3, ALBI grade 2 reduced 67.3% risk of death (HR = 0.327, 95% CI: 0.122-0.875; P = .026). Albumin-bilirubin grade was an independent predictor of survival outcome. CONCLUSION: Baseline ALBI grade is a simple and objective approach in assessing liver functions of patients with HCC. Baseline ALBI grade is an independent predictor of survival in patients treated with sorafenib.


Asunto(s)
Bilirrubina/análisis , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Albúmina Sérica/análisis , Sorafenib/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/fisiopatología , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/fisiopatología , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Centros de Atención Terciaria , Vietnam , Adulto Joven
15.
Cancer Control ; 26(1): 1073274819862793, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31290350

RESUMEN

Epidemiological characteristics of hepatocellular carcinoma (HCC) in Southern Vietnam has been well reported as in Globocan 2018 while data from the North has still not been fully presented. Therefore, we conducted this retrospective descriptive study on 198 advanced HCC patients treated at 3 major hospitals in Northern Vietnam to describe demographic features, HCC risk factors, and correlation among them in patients with advanced HCC. This information will lead to prevention efforts and provide information for allocating funds for treatment. The median age at diagnosis was 57 years (range: 19-86) and the male/female ratio was 8.9/1. The proportions of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were 81.3% and 5.6%, respectively. Hepatitis C virus infection rate was significantly higher in patients <50 years old (12.5% vs 3.3%, P = .016). There was no significant difference in age or viral hepatitis infection status by gender. Only 7.6% of patients diagnosed with advanced HCC were asymptomatic. In conclusion, with the high rate of HBV infection among patients with advanced HCC, it is necessary for increasing prevention efforts in HBV screening. Furthermore, HCV infection should be noticed in patients with advanced HCC younger than 50 years old.


Asunto(s)
Carcinoma Hepatocelular/epidemiología , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Neoplasias Hepáticas/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/virología , Femenino , Hepatitis B/patología , Hepatitis B/virología , Hepatitis C/patología , Hepatitis C/virología , Humanos , Incidencia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Vietnam/epidemiología , Adulto Joven
16.
Sensors (Basel) ; 19(3)2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30717155

RESUMEN

Thanks to the benefits of non-orthogonal multiple access (NOMA) in wireless communications, we evaluate a wireless sensor network deploying NOMA (WSN-NOMA), where the destination can receive two data symbols in a whole transmission process with two time slots. In this work, two relaying protocols, so-called time-switching-based relaying WSN-NOMA (TSR WSN-NOMA) and power-splitting-based relaying WSN-NOMA (PSR WSN-NOMA) are deployed to study energy-harvesting (EH). Regarding the system performance analysis, we obtain the closed-form expressions for the exact and approximate outage probability (OP) in both protocols, and the delay-limited throughput is also evaluated. We then compare the two protocols theoretically, and two optimization problems are formulated to reduce the impact of OP and optimize the data rate. Our numerical and simulation results are provided to prove the theoretical and analytical analysis. Thanks to these results, a great performance gain can be achieved for both TSR WSN-NOMA and PSR WSN-NOMA if optimal values of TS and PS ratios are found. In addition, the optimized TSR WSN-NOMA outperforms that of PSR WSN-NOMA in terms of OP.

17.
Nature ; 565(7737): 101-105, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30568299

RESUMEN

A defining feature of adaptive immunity is the development of long-lived memory T cells to curtail infection. Recent studies have identified a unique stem-like T-cell subset amongst exhausted CD8-positive T cells in chronic infection1-3, but it remains unclear whether CD4-positive T-cell subsets with similar features exist in chronic inflammatory conditions. Amongst helper T cells, TH17 cells have prominent roles in autoimmunity and tissue inflammation and are characterized by inherent plasticity4-7, although how such plasticity is regulated is poorly understood. Here we demonstrate that TH17 cells in a mouse model of autoimmune disease are functionally and metabolically heterogeneous; they contain a subset with stemness-associated features but lower anabolic metabolism, and a reciprocal subset with higher metabolic activity that supports transdifferentiation into TH1-like cells. These two TH17-cell subsets are defined by selective expression of the transcription factors TCF-1 and T-bet, and by discrete levels of CD27 expression. We also identify signalling via the kinase complex mTORC1 as a central regulator of TH17-cell fate decisions by coordinating metabolic and transcriptional programmes. TH17 cells with disrupted mTORC1 signalling or anabolic metabolism fail to induce autoimmune neuroinflammation or to develop into TH1-like cells, but instead upregulate TCF-1 expression and acquire stemness-associated features. Single-cell RNA sequencing and experimental validation reveal heterogeneity in fate-mapped TH17 cells, and a developmental arrest in the TH1 transdifferentiation trajectory upon loss of mTORC1 activity or metabolic perturbation. Our results establish that the dichotomy of stemness and effector function underlies the heterogeneous TH17 responses and autoimmune pathogenesis, and point to previously unappreciated metabolic control of plasticity in helper T cells.


Asunto(s)
Transdiferenciación Celular , Células Madre/citología , Células Madre/metabolismo , Células Th17/citología , Células Th17/metabolismo , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Enfermedades Autoinmunes/patología , Modelos Animales de Enfermedad , Femenino , Memoria Inmunológica/inmunología , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones , Proteína Reguladora Asociada a mTOR/deficiencia , Proteína Reguladora Asociada a mTOR/genética , Análisis de Secuencia de ARN , Transducción de Señal , Análisis de la Célula Individual , Células Madre/inmunología , Factor 1 de Transcripción de Linfocitos T/biosíntesis , Factor 1 de Transcripción de Linfocitos T/metabolismo , Proteínas de Dominio T Box/biosíntesis , Proteínas de Dominio T Box/metabolismo , Células Th17/inmunología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo
18.
Immunity ; 49(5): 899-914.e6, 2018 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-30413360

RESUMEN

Interleukin-2 (IL-2) and downstream transcription factor STAT5 are important for maintaining regulatory T (Treg) cell homeostasis and function. Treg cells can respond to low IL-2 levels, but the mechanisms of STAT5 activation during partial IL-2 deficiency remain uncertain. We identified the serine-threonine kinase Mst1 as a signal-dependent amplifier of IL-2-STAT5 activity in Treg cells. High Mst1 and Mst2 (Mst1-Mst2) activity in Treg cells was crucial to prevent tumor resistance and autoimmunity. Mechanistically, Mst1-Mst2 sensed IL-2 signals to promote the STAT5 activation necessary for Treg cell homeostasis and lineage stability and to maintain the highly suppressive phosphorylated-STAT5+ Treg cell subpopulation. Unbiased quantitative proteomics revealed association of Mst1 with the cytoskeletal DOCK8-LRCHs module. Mst1 deficiency limited Treg cell migration and access to IL-2 and activity of the small GTPase Rac, which mediated downstream STAT5 activation. Collectively, IL-2-STAT5 signaling depends upon Mst1-Mst2 functions to maintain a stable Treg cell pool and immune tolerance.


Asunto(s)
Factor de Crecimiento de Hepatocito/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Receptores de Interleucina-2/metabolismo , Factor de Transcripción STAT5/metabolismo , Transducción de Señal , Linfocitos T Reguladores/metabolismo , Animales , Autoinmunidad/genética , Autoinmunidad/inmunología , Linaje de la Célula/genética , Factor de Crecimiento de Hepatocito/genética , Vía de Señalización Hippo , Interleucina-2/metabolismo , Ratones , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Serina-Treonina Quinasa 3 , Linfocitos T Reguladores/inmunología , Proteínas de Unión al GTP rac/metabolismo
19.
Sensors (Basel) ; 18(11)2018 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-30423919

RESUMEN

In this research, we investigate a hybrid time-switching relay (TSR)⁻power-splitting relay (PSR) alternate energy harvesting (EH) relaying network over the Rician fading channels. For this purpose, the amplify-and-forward (AF) mode is considered for the alternative hybrid time TSR⁻PSR. The system model consists of one source, one destination and two alternative relays for signal transmission from the source to the destination. In the first step, the exact and asymptotic expressions of the outage probability and the symbol errors ratio (SER) are derived. Then, the influence of all system parameters on the system performance is investigated, and the Monte Carlo simulation verifies all results. Finally, the system performances of TSR⁻PSR, TSR, and PSR cases are compared in connection with all system parameters.

20.
Cell Mol Gastroenterol Hepatol ; 5(4): 678-690.e1, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29930985

RESUMEN

BACKGROUND & AIMS: Atrophic gastritis caused by chronic inflammation in the gastric mucosa leads to the loss of gastric glandular cells, including acid-secreting parietal cells. Parietal cell atrophy in a setting of chronic inflammation induces spasmolytic polypeptide expressing metaplasia, a critical step in gastric carcinogenesis. However, the mechanisms by which inflammation causes parietal cell atrophy and spasmolytic polypeptide expressing metaplasia are not well defined. We investigated the role of interleukin-17A (IL-17A) in causing parietal cell atrophy. METHODS: A mouse model of autoimmune atrophic gastritis was used to examine IL-17A production during early and late stages of disease. Organoids derived from corpus glands were used to determine the direct effects of IL-17A on gastric epithelial cells. Immunofluorescent staining was used to examine IL-17A receptors and the direct effect of signaling on parietal cells. Mice were infected with an IL-17A-producing adenovirus to determine the effects of IL-17A on parietal cells in vivo. Finally, IL-17A neutralizing antibodies were administered to mice with active atrophic gastritis to evaluate the effects on parietal cell atrophy and metaplasia. RESULTS: Increased IL-17A correlated with disease severity in mice with chronic atrophic gastritis. IL-17A caused caspase-dependent gastric organoid degeneration, which could not be rescued with a necroptosis inhibitor. Parietal cells expressed IL-17A receptors and IL-17A treatment induced apoptosis in parietal cells. Overexpressing IL-17A in vivo induced caspase-3 activation and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining in parietal cells. Finally, IL-17A neutralizing antibody decreased parietal cell atrophy and metaplasia in mice with chronic atrophic gastritis. CONCLUSIONS: These data identify IL-17A as a cytokine that promotes parietal cell apoptosis during atrophic gastritis, a precursor lesion for gastric cancer.

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