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1.
Artículo en Inglés | MEDLINE | ID: mdl-38981946

RESUMEN

A human laryngeal model, incorporating all the cartilages and the intrinsic muscles, was reconstructed based on MRI data. The vocal fold was represented as a multilayer structure with detailed inner components. The activation levels of the thyroarytenoid (TA) and cricothyroid (CT) muscles were systematically varied from zero to full activation allowing for the analysis of their interaction and influence on vocal fold dynamics and glottal flow. The finite element method was employed to calculate the vocal fold dynamics, while the one-dimensional Bernoulli equation was utilized to calculate the glottal flow. The analysis was focused on the muscle influence on the fundamental frequency (fo). We found that while CT and TA  activation increased the fo in most of the conditions, TA activation resulted in a frequency drop when it was moderately activated. We show that this frequency drop was associated with the sudden increase of the vertical motion when the vibration transited from involving the whole tissue to mainly in the cover layer. The transition of the vibration pattern was caused by the increased body-cover stiffness ratio that resulted from TA activation.

2.
World J Clin Cases ; 11(27): 6551-6557, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37900255

RESUMEN

BACKGROUND: Undifferentiated pleomorphic sarcomas, also known as spindle cell sarcomas, are a relatively uncommon subtype of soft tissue sarcomas in clinical practice. CASE SUMMARY: We present a case report of a 69-year-old female patient who was diagnosed with undifferentiated spindle cell soft tissue sarcoma on her left thigh. Surgical excision was initially performed, but the patient experienced a local recurrence following multiple surgeries and radioactive particle implantations. High-intensity focused ultrasound (HIFU) was subsequently administered, resulting in complete ablation of the sarcoma without any significant complications other than bone damage at the treated site. However, approximately four months later, the patient experienced a broken lesion at the original location. After further diagnostic workup, the patient underwent additional surgery and is currently stable with a good quality of life. CONCLUSION: HIFU has shown positive outcomes in achieving local control of limb spindle cell sarcoma, making it an effective non-invasive treatment option.

3.
J Exp Clin Cancer Res ; 42(1): 275, 2023 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-37865804

RESUMEN

BACKGROUND: Alterations in several tripartite motif-containing (TRIM) family proteins have been implicated in the pathogenesis of lung cancer. TRIM28, a member of the TRIM E3 ligase family, has been associated with tumorigenesis, cell proliferation, and inflammation. However, little is known about TRIM28 expression and its role in the immune microenvironment of non-small cell lung cancer (NSCLC). METHODS: We assessed the clinical significance of TRIM28 in tissue microarrays and TCGA cohorts. We investigated the function of TRIM28 in syngeneic mouse tumor models, the KrasLSL-G12D/+; Tp53fl/fl (KP) mouse model, and humanized mice. Immune cell composition was analyzed using flow cytometry and immunohistochemistry. RESULTS: Our findings revealed a positive correlation between TRIM28 expression and the infiltration of suppressive myeloid-derived suppressor cells (MDSCs) in NSCLC. Moreover, silencing TRIM28 enhanced the efficacy of anti-PD-1 immunotherapy by reshaping the inflamed tumor microenvironment. Mechanistically, we demonstrated that TRIM28 could physically interact with receptor-interacting protein kinase 1 (RIPK1) and promote K63-linked ubiquitination of RIPK1, which is crucial for sustaining activation of the NF-κB pathway. Mutagenesis of the E3 ligase domain corroborated the essential role of E3 ligase activity in TRIM28-mediated NF-κB activation. Further experiments revealed that TRIM28 could upregulate the expression of CXCL1 by activating NF-κB signaling. CXCL1 could bind to CXCR2 on MDSCs and promote their migration to the tumor microenvironment. TRIM28 knockdown increased responsiveness to anti-PD-1 therapy in immunocompetent mice, characterized by increased CD8+T tumor-infiltrating lymphocytes and decreased MDSCs. CONCLUSION: The present study identified TRIM28 as a promoter of chemokine-driven recruitment of MDSCs through RIPK1-mediated NF-κB activation, leading to the suppression of infiltrating activated CD8+T cells and the development of anti-PD-1 resistance. Understanding the regulation of MDSC recruitment and function by TRIM28 provides crucial insights into the association between TRIM28 signaling and the development of an immunosuppressive tumor microenvironment. These insights may inform the development of combination therapies to enhance the effectiveness of immune checkpoint blockade therapy in NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Células Supresoras de Origen Mieloide , Humanos , Ratones , Animales , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , FN-kappa B/metabolismo , Modelos Animales de Enfermedad , Microambiente Tumoral , Proteína 28 que Contiene Motivos Tripartito/genética , Proteína 28 que Contiene Motivos Tripartito/metabolismo
4.
Artículo en Inglés | MEDLINE | ID: mdl-37459263

RESUMEN

Broad learning system (BLS), which emerges as a lightweight network paradigm, has recently attracted great attention for recognition problems due to its good balance between efficiency and accuracy. However, the supervision mechanism in BLS and its variants generally relies on the strict binary label matrix, which imposes limitations on approximation and fails to adequately align with the data distribution. To address this issue, in this article, two novel flexible label-induced BLS models with the manifold manner are proposed, whose notable characteristics are as follows. First, two proposed label relaxation strategies can both enlarge the margins between different categories and simultaneously enhance the diversity within labels. Second, the integration of manifold geometrical criterion enables the models to capture local feature structures, ensuring the obtained flexible labels align better with the similarity between samples. Third, the proposed models can be optimized efficiently with the alternating direction method of multipliers. Each iteration benefits from a closed-form solution, facilitating the optimization process. Extensive experiments and thorough theoretical analysis are intended to show the advantages of our proposed models compared to other state-of-the-art recognition algorithms.

5.
BMC Plant Biol ; 23(1): 311, 2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37308826

RESUMEN

BACKGROUND: Cytoplasmic male sterility (CMS) is the basis of heterosis exploitation. CMS has been used to hybrid production in cotton, but its molecular mechanism remains unclear. CMS is associated with advanced or delayed tapetal programmed cell death (PCD), and reactive oxygen species (ROS) may mediate this process. In this study, we obtained Jin A and Yamian A, two CMS lines with different cytoplasmic sources. RESULTS: Compared with maintainer Jin B, Jin A anthers showed advanced tapetal PCD with DNA fragmentation, producing excessive ROS which accumulated around the cell membrane, intercellular space and mitochondrial membrane. The activities of peroxidase (POD) and catalase (CAT) enzymes which can scavenge ROS were significantly decreased. However, Yamian A tapetal PCD was delayed with lower ROS content, and the activities of superoxide dismutase (SOD) and POD were higher than its maintainer. These differences in ROS scavenging enzyme activities may be caused by isoenzyme gene expressions. In addition, we found the excess ROS generated in Jin A mitochondria and ROS overflow from complex III might be the source in parallel with the reduction of ATP content. CONCLUSION: ROS accumulation or abrogation were mainly caused by the joint action of ROS generation and scavenging enzyme activities transformation, which led to the abnormal progression of tapetal PCD, affected the development of microspores, and eventually contributed to male sterility. In Jin A, tapetal PCD in advance might be caused by mitochondrial ROS overproduction, accompanied by energy deficiency. The above studies will provide new insights into the cotton CMS and guide the follow-up research ideas.


Asunto(s)
Gossypium , Peroxidasa , Femenino , Embarazo , Humanos , Especies Reactivas de Oxígeno , Citoplasma , Citosol , Peroxidasas , Apoptosis
6.
Commun Biol ; 6(1): 541, 2023 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-37208428

RESUMEN

Tissue dynamics play critical roles in many physiological functions and provide important metrics for clinical diagnosis. Capturing real-time high-resolution 3D images of tissue dynamics, however, remains a challenge. This study presents a hybrid physics-informed neural network algorithm that infers 3D flow-induced tissue dynamics and other physical quantities from sparse 2D images. The algorithm combines a recurrent neural network model of soft tissue with a differentiable fluid solver, leveraging prior knowledge in solid mechanics to project the governing equation on a discrete eigen space. The algorithm uses a Long-short-term memory-based recurrent encoder-decoder connected with a fully connected neural network to capture the temporal dependence of flow-structure-interaction. The effectiveness and merit of the proposed algorithm is demonstrated on synthetic data from a canine vocal fold model and experimental data from excised pigeon syringes. The results showed that the algorithm accurately reconstructs 3D vocal dynamics, aerodynamics, and acoustics from sparse 2D vibration profiles.


Asunto(s)
Redes Neurales de la Computación , Pliegues Vocales , Animales , Perros , Pliegues Vocales/fisiología , Imagenología Tridimensional , Algoritmos , Física
7.
Heliyon ; 9(12): e22686, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38213600

RESUMEN

In this present age, innovation has become inextricably tied to both long-term economic growth and environmentally sound development. In this context, the impact that environmentally focused technological advancements or innovations have on environmental quality is of the utmost importance. Therefore, the main goal of the present study is to determine how Green innovation (GI) affects environmental degradation in the BRICS countries from 1992 to 2021. The ecological footprint (EFT) is an indicator used in the study to measure environmental degradation. The study divides the components that contribute to the explanation into two categories: the GI threshold variable and the independent variables RE, GDP, and population (POP). Additionally, this study investigates the indirect impact of RE, GDP, and POP through the threshold effect of GI. The stochastic impacts of the explanatory factors are explored using sophisticated panel data estimation methods and a panel threshold model. According to the findings of the study, an improvement in environmental quality occurs when the threshold level of GI is achieved, which indicates that innovation in the form of a lower EFT is responsible for the improvement. In light of the findings, recommendations for policymakers and stakeholders in BRICS countries are to promote RE and drive GI.

8.
Metab Eng Commun ; 15: e00211, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36311477

RESUMEN

Hemicellulose is the second most abundant carbohydrate in lignocellulosic biomass and has extensive applications. In conventional biomass refinery, hemicellulose is easily converted to unwanted by-products in pretreatment and therefore can't be fully utilized. The present study aims to summarize the most recent development of lignocellulosic polysaccharide degradation and fully convert it to value-added bioproducts through microbial and enzymatic catalysis. Firstly, bioprocess and microbial metabolic engineering for enhanced utilization of lignocellulosic carbohydrates were discussed. The bioprocess for degradation and conversion of natural lignocellulose to monosaccharides and organic acids using anaerobic thermophilic bacteria and thermostable glycoside hydrolases were summarized. Xylose transmembrane transporting systems in natural microorganisms and the latest strategies for promoting the transporting capacity by metabolic engineering were summarized. The carbon catabolite repression effect restricting xylose utilization in microorganisms, and metabolic engineering strategies developed for co-utilization of glucose and xylose were discussed. Secondly, the metabolic pathways of xylose catabolism in microorganisms were comparatively analyzed. Microbial metabolic engineering for converting xylose to value-added bioproducts based on redox pathways, non-redox pathways, pentose phosphate pathway, and improving inhibitors resistance were summarized. Thirdly, strategies for degrading lignocellulosic polysaccharides and fully converting hemicellulose to value-added bioproducts through microbial metabolic engineering were proposed.

9.
Cell Commun Signal ; 20(1): 62, 2022 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-35534896

RESUMEN

BACKGROUND: Recent studies have indicated that some members of the tripartite motif (TRIM) proteins function as important regulators for non-small cell lung cancer (NSCLC), However, the regulatory mechanism underpinning aberrant expression of TRIM in NSCLC remains unclear. Here we report that TRIM15 plays important roles in NSCLC progression through modulating Keap1-Nrf2 signaling pathway. METHODS: TRIM15 expression was evaluated by western blot analysis, tissue microarray-based immunohistochemistry analysis. The interactions between TRIM15 and Keap1 were analyzed by co-immunoprecipitation (Co-IP) and immunofluorescence co-localization assay. The correlation between TRIM15 and Keap1 was measured by Co-IP and ubiquitination analysis in vitro. Gain- and lost-of-function experiments were used to detect TRIM15 promotes proliferation and invasion of NSCLC cells both in vitro and vivo. RESULTS: Here, we revealed that TRIM15 was frequently upregulated in NSCLC samples and associated with poor prognosis. Functionally, TRIM15 knockdown resulted in decreased cancer cell proliferation and metastasis, whereas ectopic TRIM15 expression facilitated tumor cancer cell proliferation and metastasis in vitro and in vivo. Moreover, TRIM15 promoted cell proliferation and metastasis depends on its E3 ubiquitin ligase. Mechanistically, TRIM15 directly targeted Keap1 by ubiquitination and degradation, the principal regulator of Nrf2 degradation, leading to Nrf2 escaping from Keap1-mediated degradation, subsequently promoting antioxidant response and tumor progression. CONCLUSIONS: Therefore, our study characterizes the pivotal roles of TRIM15 promotes NSCLC progression via Nrf2 stability mediated by promoting Keap1 ubiquitination and degradation and could be a valuable prognostic biomarker and a potential therapeutic target in NSCLC. Video Abstract.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Proteínas de Unión al ADN , Neoplasias Pulmonares , Transducción de Señal , Ubiquitina-Proteína Ligasas , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas de Unión al ADN/metabolismo , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Neoplasias Pulmonares/patología , Factor 2 Relacionado con NF-E2/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo
10.
Ann Clin Microbiol Antimicrob ; 21(1): 12, 2022 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-35303873

RESUMEN

BACKGROUND: Legionellosis remains a public health problem. The most common diagnostic method to detect Legionella pneumophila (L. pneumophila) is culture. Polymerase chain reaction (PCR) is a fast and accurate method for this detection in environmental samples. METHODS: Four databases were searched for studies that evaluated the detection efficiency of PCR in L. pneumophila. The quality evaluation was conducted using Review Manager 5.3. We used Meta-DiSc 1.4 software and the Stata 15.0 software to create forest plots, a meta-regression, a bivariate boxplot and a Deeks' funnel plot. RESULTS: A total of 18 four-fold tables from 16 studies were analysed. The overall pooled sensitivity and specificity of PCR was 94% and 72%, respectively. The positive likelihood ratio (RLR) and negative likelihood ratio (NLR) was 2.73 and 0.12, respectively. The result of the diagnostic odds ratio (DOR) was 22.85 and the area under the curve (AUC) was 0.7884. CONCLUSION: Establishing a laboratory diagnostic tool for L. pneumophila detection is important for epidemiological studies. In this work, PCR demonstrated a promising diagnostic accuracy for L. pneumophila.


Asunto(s)
Legionella pneumophila , Bases de Datos Bibliográficas , Microbiología Ambiental , Humanos , Legionella pneumophila/genética , Legionella pneumophila/aislamiento & purificación , Oportunidad Relativa , Reacción en Cadena de la Polimerasa/métodos , Sensibilidad y Especificidad
11.
Altern Ther Health Med ; 28(6): 156-160, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33128536

RESUMEN

A 42-year-old male was hospitalized 13.5 hours after ingestion of 50 mg (approximately 0.7 mg/kg) colchicine in a suicide attempt. The patient developed gastrointestinal dysfunction, grade IV myelosuppression, and restrictive respiratory failure without occurrences of cardiovascular collapse or fatal dysrhythmias. Emergency treatment with integrated Chinese and Western medicine was started and the patient fully recovered without long-term complications. This report describes a massive overdose of colchicine successfully treated with integrated Chinese and Western medicine. Current treatment options are reviewed.


Asunto(s)
Sobredosis de Droga , Enfermedades Gastrointestinales , Adulto , China , Colchicina , Sobredosis de Droga/tratamiento farmacológico , Humanos , Masculino , Intento de Suicidio
12.
Front Psychol ; 12: 736883, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34887802

RESUMEN

Despite the fact that companies increasingly value online star endorsements as Internet celebrity economy booms, scientific knowledge on the effect of online star endorsements on consumers' purchase intention is limited. Based on the theories of self and construal level theory, this study investigates the impact of online star vs. celebrity endorsements on purchase intention and explores the underlying mechanism as well as boundary conditions. The results of four studies reveal the following: (1) Compared with no endorsement, both celebrity endorsements and online star endorsements lead to increases in consumers' purchase intention, with no significant difference between the two. (2) Self-concept mediates these relationships; specifically, celebrity and online star endorsements activate the ideal and actual self respectively, and enhance consumers' willingness to purchase. (3) The effect of endorsements on consumers' purchase intention is moderated by advertising appeals. That is, celebrity endorsements enhance purchase intention when consumers are exposed to symbolic appeals in advertisements, and online star endorsements enhance purchase intention when it is matched with functional advertising appeals.

13.
J Acoust Soc Am ; 150(2): 1176, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34470336

RESUMEN

Using a continuum model based on magnetic resonance imaging of a canine larynx, parametric simulations of the vocal fold vibration during phonation were conducted with the cricothyroid muscle (CT) and the thyroarytenoid muscle (TA) independently activated from zero to full activation. The fundamental frequency (f0) first increased and then experienced a downward jump as TA activity gradually increased under moderate to high CT activation. Proper orthogonal decomposition analysis revealed that the vocal fold vibrations were dominated by two modes representing a lateral motion and rotational motion, respectively, and the f0 drop was associated with a switch on the order of the two modes. In another parametric set where only the vocalis was active, f0 increased monotonically with both TA and CT activity and the mode switch did not occur. The results suggested that the active stress in the TA, which causes large stress differences between the body and cover, is essential for the occurrence of the rotational mode and mode switch. Relatively greater TA activity tends to promote the rotational mode, while relatively greater CT activity tends to promote the lateral mode. The results also suggested that the vibration modes affected f0 by affecting the contribution of the TA stress to the effective stiffness. The switch in the dominant mode caused the non-monotonic change of f0.


Asunto(s)
Músculos Laríngeos , Laringe , Animales , Perros , Músculos Laríngeos/diagnóstico por imagen , Fonación , Vibración , Pliegues Vocales/diagnóstico por imagen
14.
Nanoscale Res Lett ; 16(1): 126, 2021 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-34347177

RESUMEN

A MBE-prepared Gallium (Ga)-droplet surface on GaAs (001) substrate is in situ irradiated by a single shot of UV pulsed laser. It demonstrates that laser shooting can facilely re-adjust the size of Ga-droplet and a special Ga-droplet of extremely broad size-distribution with width from 16 to 230 nm and height from 1 to 42 nm are successfully obtained. Due to the energetic inhomogeneity across the laser spot, the modification of droplet as a function of irradiation intensity (IRIT) can be straightly investigated on one sample and the correlated mechanisms are clarified. Systematically, the laser resizing can be perceived as: for low irradiation level, laser heating only expands droplets to make mergences among them, so in this stage, the droplet size distribution is solely shifted to the large side; for high irradiation level, laser irradiation not only causes thermal expansion but also thermal evaporation of Ga atom which makes the size-shift move to both sides. All of these size-shifts on Ga-droplets can be strongly controlled by applying different laser IRIT that enables a more designable droplet epitaxy in the future.

15.
J Acoust Soc Am ; 150(1): 29, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34340476

RESUMEN

An MRI-based three-dimensional computer model of a canine larynx was used to investigate the effect of cricothyroid (CT) and thyroarytenoid (TA) muscle activity on vocal fold pre-phonatory posturing and glottic dynamics during voice production. Static vocal fold posturing in the full activation space of CT and TA muscles was first simulated using a laryngeal muscle mechanics model; dynamic flow-structure-acoustics interaction (FSAI) simulations were then performed to predict glottal flow and voice acoustics. The results revealed that TA activation decreased the length and increased the bulging, height, and contact area of the vocal fold. CT activation increased the length and contact area and decreased the height of the vocal fold. Both CT and TA activations increased the vocal fold stress, stiffness, and closure quotient; and only slightly affected the flow rate and voice intensity. Furthermore, CT and TA showed a complex control mechanism on the fundamental frequency pattern, which highly correlated with a combination of the stress, stiffness, and stretch of the vocal fold.


Asunto(s)
Músculos Laríngeos , Voz , Acústica , Animales , Fenómenos Biomecánicos , Perros , Músculos Laríngeos/diagnóstico por imagen , Fonación , Pliegues Vocales/diagnóstico por imagen
16.
JASA Express Lett ; 1(12): 125203, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-36154377

RESUMEN

A computational framework is proposed for virtual optimization of implant configurations of type 1 thyroplasty based on patient-specific laryngeal structures reconstructed from MRI images. Through integration of a muscle mechanics-based laryngeal posturing model, a flow-structure-acoustics interaction voice production model, a real-coded genetic algorithm, and virtual implant insertion, the framework acquires the implant configuration that achieves the optimal acoustic objectives. The framework is showcased by successfully optimizing an implant that restores acoustic features of a diseased voice resulted from unilateral vocal fold paralysis (UVFP) in producing a sustained vowel utterance. The sound intensity is improved from 62 dB (UVFP) to 81 dB (post-correction).


Asunto(s)
Laringoplastia , Laringe , Parálisis de los Pliegues Vocales , Humanos , Laringoplastia/métodos , Laringe/diagnóstico por imagen , Resultado del Tratamiento , Parálisis de los Pliegues Vocales/diagnóstico por imagen , Calidad de la Voz
17.
Artículo en Inglés | MEDLINE | ID: mdl-33082818

RESUMEN

BACKGROUND: Acupuncture at Zusanli (ST36), Quchi (LI11), and Tianshu (ST25) is commonly used in septic patients by traditional Chinese physicians. The protective effect of acupuncture at ST36 on the intestinal barrier is associated with Cholinergic Anti-Inflammatory Pathway (CAIP). However, its detailed mechanism and whether acupuncture at LI11 and ST25 have similar effects to ST36 remain unclear. AIM: To explore the effects of electroacupuncture (EA) at ST36, LI11, and ST25 on septic rats and investigate the role of the spleen in the treatment of EA at ST36. METHODS: A septic rat model caused by cecal ligation and puncture (CLP) and a postsplenectomy (SPX) CLP rat model were established. Rats were divided into nine groups depending on different treatments. Serum levels of TNF-α, IL-10, D-lactic acidosis (D-LA), double amine oxidase (DAO), and T-lymphocyte subgroup level in intestinal lymph nodes were compared. RESULTS: EA could not improve the 2-day survival of CLP rats. For CLP rats, EA at ST36 and LI11 significantly decreased the levels of TNF-α, IL-10, DAO, and D-LA in serum and normalized intestinal T-cell immunity. For SPX CLP rats, EA at ST36 failed to reduce serum concentrations of TNF-α, IL-10, and D-LA but increased the values of CD3+CD4+/CD3+CD8+ cells and Treg/Th17 cells. CONCLUSIONS: EA at ST36 and LI11, respectively, could alleviate inflammation reaction, protect the intestinal barrier, and maintain intestinal T-cell function in septic rats. Spleen participated in the protective effect of EA at ST36 in sepsis.

18.
J Exp Clin Cancer Res ; 39(1): 176, 2020 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-32867817

RESUMEN

BACKGROUND: Exosomes are emerging as important mediators of the cross-talk between tumor cells and the microenvironment. The communication between tumor-derived exosomes and macrophages has a critical role in facilitating tumor progression. However, the mechanisms by which exosomes modulate tumor development in lung cancer are not fully understood. METHODS: Short hairpin RNA mediated knockdown or exogenous expression of TRIM59 combined with in vitro and in vivo assays were performed to prove the functional significance of TRIM59. Western blotting, real-time PCR, co-immunoprecipitation, immunofluorescence (IF) staining assays, proximity ligation assay (PLA), ubiquitination assays, lactate secretion and lipid droplets content measurement, and rescue experiments were used to evaluate the mechanism. Lewis lung carcinoma (LLC) cells were injected via subcutaneously or tail vein into C57BL/6 wild-type (WT) and transgenic mice to assess the role of TRIM59 in vivo. RESULTS: We demonstrated that tripartite motif-containing 59 (TRIM59) was expressed in lung cancer cells-derived exosomes, and can be transferred to macrophages through the exosomes. Activated macrophages by TRIM59 promote lung cancer progression in vitro and in vivo. Mechanistic investigations revealed that TRIM59 physically interacts with abhydrolase domain containing 5 (ABHD5) and directly induced the ubiquitination of ABHD5 and led to its proteasome-dependent degradation. ABHD5, an lipolytic co-activator, deficiency induced metabolic reprogramming and enabled NLRP3 inflammasome activation in macrophages. Further studies showed that the exacerbation of NLRP3 inflammasome activation by ABHD5 deficiency, provides a positive feedback loop to promote cancer progression by preferentially secrete the proinflammatory cytokine IL-1ß. CONCLUSIONS: Collectively, these data indicate that tumor-derived exosomal TRIM59 converts macrophages to tumor-promoting functions of macrophages via regulating ABHD5 proteasomal degradation, to activate NLRP3 inflammasome signaling pathway to promote lung cancer progression by IL-1ß secretion. Our findings also indicate that tumor-derived exosomal TRIM59 has an important role in intercellular communication for fostering an inflammatory microenvironment and promoting lung metastasis.


Asunto(s)
Carcinoma Pulmonar de Lewis/patología , Exosomas/metabolismo , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Pulmonares/secundario , Macrófagos/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Pulmonar de Lewis/inmunología , Carcinoma Pulmonar de Lewis/metabolismo , Proliferación Celular , Humanos , Inflamasomas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteínas de Motivos Tripartitos/genética , Células Tumorales Cultivadas , Microambiente Tumoral
19.
J Acoust Soc Am ; 147(4): 2597, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32359330

RESUMEN

In this work, a high-fidelity three-dimensional continuum model of the canine laryngeal framework was developed for simulating laryngeal posturing. By building each muscle and cartilage from magnetic resonance imaging (MRI), the model is highly realistic in anatomy. The muscle mechanics is modeled using the finite-element method. The model was tested by simulating vocal fold postures under systematic activations of individual as well as groups of laryngeal muscles, and it accurately predicted vocal fold posturing parameters reported from in vivo canine larynges. As a demonstration of its application, the model was then used to investigate muscle controls of arytenoid movements, medial surface morphology, and vocal fold abduction. The results show that the traditionally categorized adductor and abductor muscles can have opposite effects on vocal fold posturing, making highly complex laryngeal adjustments in speech and singing possible. These results demonstrate that a realistic comprehensive larynx model is feasible, which is a critical step toward a causal physics-based model of voice production.


Asunto(s)
Laringe , Pliegues Vocales , Animales , Fenómenos Biomecánicos , Perros , Músculos Laríngeos/diagnóstico por imagen , Laringe/diagnóstico por imagen , Imagen por Resonancia Magnética , Pliegues Vocales/diagnóstico por imagen , Vocalización Animal
20.
J Sci Food Agric ; 100(5): 2136-2144, 2020 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-31884697

RESUMEN

BACKGROUND: Nitric oxide (NO) and abscisic acid (ABA) are important regulators of plant response to cold stress, and they interact in response to cold signals. The primary goal of this study was to determine the roles of exogenous NO and ABA on the synthesis of endogenous NO and ABA in cold-stored peach fruit. RESULTS: Exogenous NO and ABA maintained a relatively high content of NO, increased nitrate reductase (NR) activity, and inhibited the activity of NO synthase (NOS)-like and the levels of polyamine biosynthesis in peaches during cold storage. Treatments of potassium 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), NO, N-nitro-l-Arg-methyl ester (L -NAME), and sodium tungstate did not influence ABA content. Exogenous ABA increased the content of carotenoids and the activities of aldehyde oxidase (AO), 9-cis-epoxycarotenoid dioxygenase (NCED), and zeaxanthin epoxidase (ZEP) of ABA synthesis in peaches during cold storage, and upregulated the gene expression of PpAO1, PpNCED1, PpNCED2, and PpZEP. The production of endogenous NO was differentially inhibited by NO scavengers, ABA inhibitors, and NR inhibitors, but not affected by NOS-like inhibitors during cold storage. CONCLUSION: Exogenous NO and ABA can induce endogenous NO synthesis in cold-stored peaches by the nitrate reductase pathway, and ABA can mediate endogenous ABA synthesis by the autocatalytic reaction. NO does not regulate ABA synthesis. © 2019 Society of Chemical Industry.


Asunto(s)
Ácido Abscísico/metabolismo , Óxido Nítrico/metabolismo , Prunus persica/metabolismo , Adenosilmetionina Descarboxilasa/metabolismo , Aldehído Oxidasa , Arginina/análisis , Carboxiliasas/metabolismo , Dioxigenasas , Almacenamiento de Alimentos , Frutas/metabolismo , Regulación de la Expresión Génica de las Plantas , Nitratos/análisis , Óxido Nítrico Sintasa/metabolismo , Nitritos/análisis , Oxidorreductasas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Espermidina/análisis , Espermina/análisis
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