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1.
Front Bioeng Biotechnol ; 12: 1436702, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39219622

RESUMEN

Introduction: Assessing the influence of respiratory assistive devices on the diaphragm mobility is essential for advancing patient care and improving treatment outcomes. Existing respiratory assistive robots have not yet effectively assessed their impact on diaphragm mobility. In this study, we introduce for the first time a non-invasive, real-time clinically feasible ultrasound method to evaluate the impact of soft wearable robots on diaphragm displacement. Methods: We measured and compared diaphragm displacement and lung volume in eight participants during both spontaneous and robotic-assisted respiration. Building on these measurements, we proposed a human-robot coupled two-compartment respiratory mechanics model that elucidates the underlying mechanism by which our extracorporeal wearable robots augments respiration. Specifically, the soft robot applies external compression to the abdominal wall muscles, inducing their inward movement, which consequently pushes the diaphragm upward and enhances respiratory function. Finally, we investigated the level and shape of various robotic assistive forces on diaphragm motion. Results: This robotic intervention leads to a significant increase in average diaphragm displacement by 1.95 times and in lung volume by 2.14 times compared to spontaneous respiration. Furthermore, the accuracy of the proposed respiratory mechanics model is confirmed by the experimental results, with less than 7% error in measurements of both diaphragm displacement and lung volume. Finally, the magnitude of robotic assistive forces positively correlates with diaphragm movement, while the shape of the forces shows no significant relationship with diaphragm activity. Conclusion: Our experimental findings validate the effective assistance mechanism of the proposed robot, which enhances diaphragm mobility and assists in ventilation through extracorporeal robotic intervention. This robotic system can assist with ventilation while increasing diaphragm mobility, potentially resolving the issue of diaphragm atrophy. Additionally, this work paves the way for improved robotic designs and personalized assistance, tailored to the dynamics of the diaphragm in respiratory rehabilitation.

2.
Int Immunopharmacol ; 142(Pt B): 113079, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39288628

RESUMEN

Pancreatic cancer has emerged as one of the most lethal malignancies, characterized by rising morbidity and mortality rates. Research has demonstrated that N6-methyladenosine (m6A) modification of RNA significantly influences RNA metabolism, and dysregulation of m6A is implicated in various human diseases. A clearer picture of how the divergent m6A methylation patterns affect immunological microenvironment in pancreatic cancer is still unknown. Based on an analysis of RNA-sequencing (RNA-seq) data from the TCGA, GEO, and GTEx databases, we predicted and validated the expression of YTHDF2. Apoptosis and cell cycle analyses of YTHDF2 were conducted using flow cytometry, and a subcutaneous transplantation tumor model was established in BALB/c nude mice. The immune infiltration status and Weighted Gene Co-expression Network Analysis (WGCNA) were employed to evaluate cellular immunity and identify downstream target genes associated with the CD8+ T cell module. Additionally, machine learning-based integrative approaches were utilized to generate a predictive signature. The Western blot technique was employed to quantify YTHDF2 expression levels in PDAC cell lines and tissues. WGCNA and PPI unveiled TFG as the core gene regulation network conducting the function of the CD8+ T cell. Quantitative reverse transcription PCR (qRT-PCR) assays were conducted to confirm the reduction in TFG expression subsequent to YTHDF2 knockdown. Integrative analyses using large-scale genomic data sets were conducted to reveal that YTHDF2 could affect pancreatic cancer cell apoptosis and the cell cycle, promote malignant biologic processes, and gene regulation in immune cells. YTHDF2 potentially modulates crucial molecular subgroups of immune checkpoint molecules in CD8+ T cells, thereby enhancing tumor immunogenicity and promoting anti-tumor immune responses.

3.
FASEB J ; 38(17): e70028, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39235355

RESUMEN

Pancreatic cancer is a highly aggressive and lethal carcinoma. Circular RNAs (circRNAs) serve key regulatory functions in pancreatic cancer. Ferroptosis was induced by erastin treatment and analyzed by examining malondialdehyde (MDA), iron, Fe2+ and glutathione (GSH). C11-BODIPY 581/591 was used to stain cells for analyzing lipid peroxidation. RNA immunoprecipitation, pull-down and chromatin immunoprecipitation assays were applied to evaluate intermolecular interaction. Mice received subcutaneous injection of pancreatic cancer cells as a model of subcutaneous tumor for in vivo tests. Circ_0005397 was abundantly expressed in pancreatic cancer, and its upregulation was associated with low survival of patients with pancreatic cancer. Circ_0005397 expression was induced by EIF4A3. PCBP2 was highly expressed in pancreatic cancer, and circ_0005397 and PCBP2 were positively correlated in patients with pancreatic cancer. Circ_0005397 knockdown sensitized pancreatic carcinoma cells to ferroptosis via downregulating PCBP2. Circ_0005397 promoted PCBP2 transcription via facilitating the binding of KAT6A and H3K9ac to PCBP2 promoter. Silencing of circ_0005397 reduced tumor growth by enhancing erastin-induced ferroptosis in vivo. EIF4A3-induced circ_0005397 inhibited erastin-induced ferroptosis in pancreatic cancer by promoting PCBP2 expression through KAT6A and H3K9ac.


Asunto(s)
Ferroptosis , Neoplasias Pancreáticas , ARN Circular , Proteínas de Unión al ARN , Ferroptosis/genética , Humanos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/genética , ARN Circular/genética , ARN Circular/metabolismo , Animales , Ratones , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Masculino , Regulación hacia Arriba , Ratones Endogámicos BALB C
4.
Water Res ; 262: 122084, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39018578

RESUMEN

Global land-use changes alter the delivery of fluvial dissolved organic matter (DOM) along land-to-sea continuum. To study how spatial variations in watershed anthropogenic disturbances control chemodiversity and reactivity of DOM exported to oceans, we used fluorescent and ultra-high-resolution mass spectrometry to investigate spatial and seasonal variations of DOM properties along two subtropical coastal rivers with contrasting anthropogenic land-use distributions (North and West tributaries of Jiulong River, southeast China). Dissolved organic carbon (DOC) concentration and humic- and protein-like fluorescent DOM (FDOM) intensities were high in the mixed urban-agricultural impacted upper North River and lower West River. DOM molecular signatures suggested that the urban-sourced DOM is dominated by bio-labile, S-rich compounds, whereas the agricultural-sourced DOM is characterized by a mixture of bio-labile CHONS and bio-refractory CHON. This anthropogenic-induced spatial variation in DOM signatures was especially prominent during the dry season. Molecular analysis indicated that heteroatomic-containing (phosphorus-sulfur-nitrogen) DOM compounds are more biologically degradable, whereas most of the heteroatom-depleted and highly unsaturated CHO was stable during transport. Due to a longer transit distance and reservoir impoundment in North River, the urban-sourced aliphatic compounds were largely microbially removed or transformed into bio-refractory components, resulting in lower DOC fluxes and an increase of recalcitrance in the DOM exported to the ocean. Conversely, shorter transit times for anthropogenic inputs from the middle/lower West River increased watershed yield and export fluxes of DOC with higher bio-lability. Our study documents that transit history plays a crucial role in assessing the fate of anthropogenic DOM along the land-to-ocean continuum.


Asunto(s)
Océanos y Mares , Ríos , Ríos/química , China , Monitoreo del Ambiente , Estaciones del Año , Compuestos Orgánicos/análisis , Efectos Antropogénicos , Carbono/análisis , Agua de Mar/química
5.
Sensors (Basel) ; 24(12)2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38931614

RESUMEN

Traditional switching operations require on-site work, and the high voltage generated by arc discharges can pose a risk of injury to the operator. Therefore, a combination of visual servo and robot control is used to localize the switching operation and construct hand-eye calibration equations. The solution to the hand-eye calibration equations is coupled with the rotation matrix and translation vectors, and it depends on the initial value determination. This article presents a convex relaxation global optimization hand-eye calibration algorithm based on dual quaternions. Firstly, the problem model is simplified using the mathematical tools of dual quaternions, and then the linear matrix inequality convex optimization method is used to obtain a rotation matrix with higher accuracy. Afterwards, the calibration equations of the translation vectors are rewritten, and a new objective function is established to solve the coupling influence between them, maintaining positioning precision at approximately 2.9 mm. Considering the impact of noise on the calibration process, Gaussian noise is added to the solutions of the rotation matrix and translation vector to make the data more closely resemble the real scene in order to evaluate the performance of different hand-eye calibration algorithms. Eventually, an experiment comparing different hand-eye calibration methods proves that the proposed algorithm is better than other hand-eye calibration algorithms in terms of calibration accuracy, robustness to noise, and stability, satisfying the accuracy requirements of switching operations.

6.
IEEE Trans Biomed Eng ; 71(10): 2923-2935, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38753478

RESUMEN

OBJECTIVE: Respiratory regulation is critical for patients with respiratory dysfunction. Clinically used ventilators can lead to long-term dependence and injury. Extracorporeal assistance approaches such as iron-lung devices provide a noninvasive alternative, however, artificial actuator counterparts have not achieved marvelous biomimetic ventilation as human respiratory muscles. Here, we propose a bionic soft exoskeleton robot that can achieve extracorporeal closed-loop respiratory regulation by emulating natural human breath. METHODS: For inspiration, a soft vacuum chamber is actuated to produce negative thoracic pressure and thus expand lung volume by pulling the rib cage up and outward through use of external negative pressure. For expiration, a soft origami array under positive pressure pushes the abdominal muscles inward and the diaphragm upward. To achieve in vitro measurement of respiratory profile, we describe a wireless respiratory monitoring device to measure respiratory profiles with high accuracy, validated by quantitative comparisons with spirometer as gold-standard reference. By constructing a human-robot coupled respiratory mechanical model, a model-based proportional controller is designed for continuous tracking of the target respiratory profile. RESULTS: In experiments with ten healthy participants and ten patients with respiratory difficulty, the robot can adjust its assistive forces in real time and drive human-robot coupling respiratory system to track the target profile. CONCLUSION: The biomimetic robot can achieve extracorporeal closed-loop respiratory regulation for a diverse population. SIGNIFICANCE: The soft robot has important potential to assist respiration for people with respiratory difficulty, whether in a hospital or a home setting.


Asunto(s)
Robótica , Humanos , Robótica/instrumentación , Robótica/métodos , Adulto , Masculino , Biónica , Diseño de Equipo , Femenino , Persona de Mediana Edad , Dispositivo Exoesqueleto , Respiración Artificial/instrumentación , Respiración Artificial/métodos , Anciano
7.
Plants (Basel) ; 13(10)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38794388

RESUMEN

The glutathione S-transferases (GSTs, EC 2.5.1.18) constitute a versatile enzyme family with pivotal roles in plant stress responses and detoxification processes. Recent discoveries attributed the additional function of facilitating anthocyanin intracellular transportation in plants to GSTs. Our study identified 178 VcGST genes from 12 distinct subfamilies in the blueberry genome. An uneven distribution was observed among these genes across blueberry's chromosomes. Members within the same subfamily displayed homogeneity in gene structure and conserved protein motifs, whereas marked divergence was noted among subfamilies. Functional annotations revealed that VcGSTs were significantly enriched in several gene ontology and KEGG pathway categories. Promoter regions of VcGST genes predominantly contain light-responsive, MYB-binding, and stress-responsive elements. The majority of VcGST genes are subject to purifying selection, with whole-genome duplication or segmental duplication serving as key processes that drive the expansion of the VcGST gene family. Notably, during the ripening of the blueberry fruit, 100 VcGST genes were highly expressed, and the expression patterns of 24 of these genes demonstrated a strong correlation with the dynamic content of fruit anthocyanins. Further analysis identified VcGSTF8, VcGSTF20, and VcGSTF22 as prime candidates of VcGST genes involved in the anthocyanin intracellular transport. This study provides a reference for the exploration of anthocyanin intracellular transport mechanisms and paves the way for investigating the spectrum of GST functions in blueberries.

8.
Nat Commun ; 15(1): 4490, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802424

RESUMEN

Mercury (Hg), a potent neurotoxin posing risks to human health, is cycled through vegetation uptake, which is susceptible to climate change impacts. However, the extent and pattern of these impacts are largely unknown, obstructing predictions of Hg's fate in terrestrial ecosystems. Here, we evaluate the effects of climate change on vegetation elemental Hg [Hg(0)] uptake using a state-of-the-art global terrestrial Hg model (CLM5-Hg) that incorporates plant physiology. In a business-as-usual scenario, the terrestrial Hg(0) sink is predicted to decrease by 1870 Mg yr-1 in 2100, that is ~60% lower than the present-day condition. We find a potential decoupling between the trends of CO2 assimilation and Hg(0) uptake process by vegetation in the 21st century, caused by the decreased stomatal conductance with increasing CO2. This implies a substantial influx of Hg into aquatic ecosystems, posing an elevated threat that warrants consideration during the evaluation of the effectiveness of the Minamata Convention.


Asunto(s)
Dióxido de Carbono , Cambio Climático , Ecosistema , Mercurio , Plantas , Dióxido de Carbono/metabolismo , Mercurio/metabolismo , Plantas/metabolismo
9.
Sci Data ; 11(1): 399, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643170

RESUMEN

Dynamical downscaling is vital for generating finer-scale climate projections. Recently, a set of simulations under four types of 1.5/2 °C global warming scenarios are available with Nanjing University of Information Science and Technology Earth System Model (NESM). However, NESM3's bias in large-scale driving variables would degrade downscaled simulations. We corrected NESM3 bias in terms of climate mean and inter-annual variance against ERA5 using a novel bias correction method and then produced a set of bias-corrected datasets for dynamical downscaling. The bias-corrected NESM3 spans the historical period for 1979-2014 and four future scenarios (i.e., 1.5 °C overshoot for 2070-2100, stabilized 1.5/2 °C for 2070-2100, and transient 2 °C for 2031-2061) with 1.25° × 1.25° horizontal resolution at six-hourly intervals. Our evaluation suggests that bias-corrected NESM3 outperforms the original NESM3 in the climatological mean of seasonal mean and variability, as well as climate extreme events during the historical period. This bias-corrected dataset is expected to generate more reliable projections for regional climate and environment under 1.5/2 °C global warming.

10.
IEEE Trans Haptics ; PP2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38393841

RESUMEN

Pneumatic tactile displays dynamically customize surface morphological features with reconfigurable arrays of independently addressable actuators. However, their ability to render detailed tactile patterns or fine textures is limited by the low spatial resolution. For pneumatic tactile displays, the high-density integration of pneumatic actuators within a small space (fingertip) poses a significant challenge in terms of pneumatic circuit wiring. In contrast to the structure with a single-layer layout of pipes, we propose a multi-layered stacked microfluidic pipe structure that allows for a higher density of actuators and retains their independent actuation capabilities. Based on the proposed structure, we developed a soft microfluidic tactile display with a spatial resolution of 1.25 mm. The device consists of a 5 × 5 array of independently addressable microactuators, driven by pneumatic pressure, each of which enables independent actuation of the surface film and continuous control of the height. At a relative pressure of 1000 mbar, the actuator produced a perceptible out-of-plane deformation of 0.145 mm and a force of 17.7 mN. User studies showed that subjects can easily distinguish eight tactile patterns with 96% accuracy.

11.
Artículo en Inglés | MEDLINE | ID: mdl-38064610

RESUMEN

Objective: To assess lower extremity deep vein thrombosis (DVT) risk factors after artificial femoral head replacement for elderly femoral neck fractures. A nomogram model was constructed to predict its risk. Methods: In analyzing 144 participants who underwent artificial femoral head replacement for elderly femoral neck fractures, researchers collected clinical data to identify factors associated with lower extremity DVT. The study collected numerous variables ranging from age and sex to history of lower extremity DVT and use of anticoagulant drugs after surgery. The patients were in two groups: those who developed DVT (n = 62) and those who did not (n = 82). Multivariate logistic regression analysis helped to identify factors influencing the occurrence of DVT after artificial femoral head replacement. The software packages used were R 4.1.0 and RMS. Results: Univariate and multivariate regression analysis identified age, ASA level, D-dimer of lower limb DVT, ALB, and PLT as predictive risk factors of lower extremity DVT after artificial femoral head replacement for elderly femoral neck fractures. Those risk factors were used to construct a clinical predictive nomogram. The calibration curves for hypertension in patients with OSAHS risk revealed excellent accuracy of the predictive nomogram model. The unadjusted concordance index (C-index) for the model was 0.877 [95% confidence interval (CI), 0.805-0.942]. The AUC was 0.8375002. Decision curve analysis showed that the predictive model could be applied clinically when the threshold probability was 20 to 80%. Conclusions: The researchers constructed and validated a clinical nomogram to predict the occurrence of lower extremity DVT after artificial femoral head replacement in elderly patients with femoral neck fractures. Age, ASA level, D-dimer, and history of lower limb DVT, ALB, and PLT were demonstrated to be predictive risk factors of lower extremity DVT in this circumstance. This practical prognostic nomogram may help improve clinical decision-making.

12.
Artículo en Inglés | MEDLINE | ID: mdl-37955998

RESUMEN

The perception of voluntary respiratory consciousness is quite important in some situations, such as respiratory assistance and respiratory rehabilitation training, and the key signatures about voluntary respiration control may lie in the neural signals from brain manifested as electroencephalography (EEG). The present work aims to explore whether there exists correlation between voluntary respiration and scalp EEG. Evoke voluntary respiration of different intensities, while collecting EEG and respiration signal synchronously. Data from 11 participants were analyzed. Spectrum characteristics at low-frequency band were studied. Computation of EEG-respiration phase lock value (PLV) and EEG sample entropy were conducted as well. When breathing voluntarily, the 0-2 Hz band EEG power is significantly enhanced in frontal and right-parietal area. The distance between main peaks belonging to the two signals in 0-2 Hz spectrum graph tends to get smaller, while EEG-respiration PLV increases in frontal area. Besides, the sample entropy of EEG shows a trend of decreasing during voluntary respiration in both areas. There's a strong correlation between voluntary respiration and scalp EEG. Significance: The discoveries will provide guidelines for developing a voluntary respiratory consciousness identifying method and make it possible to monitor people's intention of respiration by noninvasive BCI.


Asunto(s)
Electroencefalografía , Respiración , Humanos , Electroencefalografía/métodos , Encéfalo/fisiología , Frecuencia Respiratoria , Estado de Conciencia
13.
BMC Musculoskelet Disord ; 24(1): 834, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37872547

RESUMEN

BACKGROUND: To retrospectively analyse postoperative adverse events in oldest-old patients (aged 90 years and older) with intertrochanteric fractures treated under various anaesthetic techniques. METHODS: A total of 153 consecutive patients participated in this study, of which 127 patients who underwent surgery with neuraxial anaesthesia or general anaesthesia for intertrochanteric fractures between October 2019 and October 2022 were eligible and evaluated. They were divided into the neuraxial anaesthesia and general anaesthesia groups. The demographic characteristics and postoperative adverse events were compared between the two groups. RESULTS: A total of 13 patients (10.24%), including 6 in the neuraxial anaesthesia group (8.22%) and 7 in the general anaesthesia group (12.96%), died within 30 days after surgery. No significant differences between the two groups were observed. Postoperative delirium occurred in 40 patients (31.49%), including 17 (23.29%) in the neuraxial anaesthesia group and 23 (42.59%) in the general anaesthesia group; there was a significant difference between the two groups [P = 0.02, odds ratio (OR) = 0.41]. The other postoperative adverse events, including heart failure, acute stroke, acute myocardial infarction, pulmonary disease, anaemia, deep vein thrombosis, hypoproteinaemia, and electrolyte disorders, were not significantly different between the two groups. CONCLUSION: Our data suggest that different anaesthesia methods do not affect the incidence of adverse events, such as death within 30 days after surgery in oldest-old patients with intertrochanteric fractures. However, more patients developed delirium after surgery in the general anaesthesia group (23, 42.59%) than in the neuraxial anaesthesia group (17, 23.29%); this may indicate that spinal anaesthesia reduces the incidence of postoperative delirium (P = 0.02, OR = 0.41). TRIAL REGISTRATION: Retrospectively registered.


Asunto(s)
Delirio del Despertar , Fracturas de Cadera , Humanos , Anciano de 80 o más Años , Estudios Retrospectivos , Delirio del Despertar/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anestesia General/efectos adversos , Fracturas de Cadera/cirugía , Fracturas de Cadera/etiología
14.
Diagn Microbiol Infect Dis ; 107(4): 116067, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37751629

RESUMEN

Treatment at the early stage of onset is vital for the prognosis of rickettsioses. But the absence of specific clinical symptoms complicates the diagnosis of this condition. Herein we established a seminested recombinase polymerase amplification assay (snRPA-nfo) that enables quick detection and differentiation of rickettsial pathogens in clinical samples with high sensitivity and specificity. The conserved 17-kDa protein gene of Rickettsia sibirica and the 47-kDa protein gene of Orientia tsutsugamushi were targeted for the duplex RPA-nfo assay. The snRPA-nfo assay exhibited an increased LOD in spiked blood samples, up to 1000-fold in comparison to standard RPA-nfo, and a better detection rate (83.3%, 5/6) than TaqMan PCR (16.6%, 1/6, Ct ≤ 35) in clinically confirmed patient blood samples. Thus, snRPA-nfo assay represents a promising alternative to TaqMan PCR in the early diagnosis of rickettsioses for point-of-care testing as well as in resource-limited settings.


Asunto(s)
Orientia tsutsugamushi , Infecciones por Rickettsia , Humanos , Recombinasas , Sensibilidad y Especificidad , Reacción en Cadena de la Polimerasa , Orientia tsutsugamushi/genética , Técnicas de Amplificación de Ácido Nucleico , Infecciones por Rickettsia/diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa
15.
J Fungi (Basel) ; 9(7)2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37504767

RESUMEN

Blueberry (Vaccinium spp.) rhizosphere microorganisms can significantly increase the absorption area and improve the efficiency of rhizospheric nutrient uptake. However, there has been little research on blueberry rhizosphere microorganisms, especially those that can complement root function deficiency. In this study, we analyzed the rhizosphere fungi of 'O'Neal,' 'Sharpblue,' and 'Premier' blueberry cultivars and found that 'Premier' blueberries showed strong growth potential and relatively high root regulation ability. The dominant symbiotic fungus Sistotrema was correlated with the strong growth of 'Premier' and was directionally screened and isolated based on conserved gene structures and COG function analysis. This fungus was reinoculated onto the roots of 'Gulfcoast' and 'Star' blueberry cultivars. Sistotrema promoted the growth of blueberries and improved their ability to resist stress and grow under adverse conditions, as indicated by maintained or increased chlorophyll content under such conditions. Further analyses showed that Sistotrema has certain functional characteristics such as the ability to dissolve iron in its insoluble form and then release it, to fix nitrogen, and to inhibit nitrification in soil. Thus, it effectively doubled the soil nitrogen content and increased the soluble iron content in soil by 50%. This investigation indicates sistotrema inoculation as an approach to increase blueberry stress tolerance and complete their root nutrition deficiency.

16.
Mol Med Rep ; 28(3)2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37449516

RESUMEN

N6-methyl-adenosine (m6a) is involved in the occurrence and development of various diseases such as autogenic immune disease and tumors. Methyltransferases regulate primary (pri)-microRNA (miRNA/miR) processing by mediating m6a modifications, consequently affecting pathological processes including immune-related diseases by regulating both innate and adaptive immune cells. However, the roles of m6a on the biological functions of bone marrow mesenchymal stem cells (BMSCs) remain to be elucidated. The relative expression levels of methyltransferase-like 14 (METTL14) and other methyltransferases, demethylases, and miR-873 in bone samples from patients with osteoporosis and from normal individuals were measured by reverse transcription-quantitative PCR. Cell Counting Kit-8 assay was used to examine the proliferation of BMSCs. Co-immunoprecipitation (Co-IP) was used to investigate the binding of METTL14 to DiGeorge syndrome critical region 8 (DGCR8). RNA immunoprecipitation (RIP) was used to examine the binding of METTL14 to pri-miR-873. METTL14 and m6a modifications were highly detected in patients with osteoporosis compared with the controls. Co-IP results indicated that silencing of METTL14 reduced METTL14 and m6a modification levels in BMSCs. Downregulation of METTL14 significantly promoted the proliferation of BMSCs. RIP results suggested that METTL14/m6a methylation modification promoted the processing of pri-miR-873 by binding to DGCR8 in BMSCs. Furthermore, overexpression of miR-873 inhibited the proliferation of BMSCs. The results also showed that miR-873 mimics significantly inhibited the proliferation in small interfering (si)-METTL14 transfected BMSCs; however, miR-873 inhibitors markedly promoted the proliferation of si-METTL14 transfected BMSCs. METTL14 and m6a modifications were upregulated in osteoporosis samples. METTL14 promoted the processing of pri-miR-873 into mature miR-873 by regulating m6a modification. Furthermore, overexpression of miR-873 significantly inhibited the proliferation of BMSCs. Therefore, the METTL14/m6a/miR-873 axis may be a potential target for the treatment of osteoporosis.


Asunto(s)
Células Madre Mesenquimatosas , MicroARNs , Osteoporosis , Humanos , MicroARNs/metabolismo , Proteínas de Unión al ARN/metabolismo , Diferenciación Celular/genética , Osteogénesis/genética , Osteoporosis/metabolismo , Células Madre Mesenquimatosas/metabolismo , Proliferación Celular/genética , Células de la Médula Ósea , Metiltransferasas/genética , Metiltransferasas/metabolismo
17.
Plant Physiol ; 193(2): 1381-1394, 2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37437116

RESUMEN

Photorespiration begins with the oxygenation reaction catalyzed by Rubisco and is the second highest metabolic flux in plants after photosynthesis. Although the core biochemical pathway of photorespiration has been well characterized, little is known about the underlying regulatory mechanisms. Some rate-limiting regulation of photorespiration has been suggested to occur at both the transcriptional and posttranslational levels, but experimental evidence is scarce. Here, we found that mitogen-activated protein kinase 2 (MAPK2) interacts with photorespiratory glycolate oxidase and hydroxypyruvate reductase, and the activities of these photorespiratory enzymes were regulated via phosphorylation modifications in rice (Oryza sativa L.). Gas exchange measurements revealed that the photorespiration rate decreased in rice mapk2 mutants under normal growth conditions, without disturbing photosynthesis. Due to decreased photorespiration, the levels of some key photorespiratory metabolites, such as 2-phosphoglycolate, glycine, and glycerate, significantly decreased in mapk2 mutants, but those of photosynthetic metabolites were not altered. Transcriptome assays also revealed that the expression levels of some flux-controlling genes in photorespiration were significantly downregulated in mapk2 mutants. Our findings provide molecular evidence for the association between MAPK2 and photorespiration and suggest that MAPK2 regulates the key enzymes of photorespiration at both the transcriptional and posttranslational phosphorylation levels in rice.


Asunto(s)
Oryza , Oryza/fisiología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Fotosíntesis/genética , Plantas/metabolismo , Dióxido de Carbono/metabolismo
18.
Plants (Basel) ; 12(14)2023 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-37514210

RESUMEN

BRANCHED1 (BRC1) is a crucial member of the TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) gene family and is well known for playing a central role in shoot branching by controlling buds' paradormancy. However, the expression characteristics and molecular regulatory mechanism of BRC1 during blueberry bud dormancy are unclear. To shed light on these topics, shoots of three blueberry cultivars with different chilling requirements (CRs) were decapitated in summer to induce paradormancy release and subjected to different levels of chilling in winter to induce endodormancy release. The results showed that the high-CR cultivar 'Chandler' had the strongest apical dominance among the three cultivars; additionally, the expression of VcTCP18, which is homologous to BRC1, was the highest under both the decapitation treatment and low-temperature treatment. The 'Emerald' cultivar, with a low CR, demonstrated the opposite trend. These findings suggest that VcTCP18 plays a negative regulatory role in bud break and that there may be a correlation between the CR and tree shape. Through yeast 1-hybrid (Y1H) assays, we finally screened 21 upstream regulatory genes, including eight transcription factors: zinc-finger homeodomain protein 1/4/5/9, MYB4, AP2-like ethylene-responsive transcription factor AINTEGUMENTA (ANT), ASIL2-like, and bHLH035. It was found that these upstream regulatory genes positively or negatively regulated the expression of VcTCP18 based on the transcriptome expression profile. In summary, this study enriched our understanding of the regulatory network of BRCl during bud dormancy and provided new insights into the function of BRC1.

19.
J Surg Oncol ; 128(4): 510-518, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37272486

RESUMEN

BACKGROUND: Malignant pheochromocytoma/paraganglioma (PCPG) is lethal and difficult to diagnose before metastasis. This study is aiming to characterize the PCPG and explore novel prognostic markers. METHODS: Clinical data of patients with pathologically confirmed invasive and noninvasive PCPG were collected and analyzed. Then, the differentially expressed genes (DEGs) and HUB genes were identified by R package "limma" in GSE67066-GPL570. Afterward, the prognostic markers were screened out using R packages of "survival" and "survminer" based on the TCGA data. RESULTS: The 34 invasive PCPGs were characterized by irregular contour and unclear boundary on CT and capsule/extracapsule tissue invasion on pathology compared with the 42 noninvasive PCPGs. Then, 29 upregulated and 30 downregulated DEGs were identified in malignant PCPG compared with benign, which were mainly enriched in the terms of calcium ion binding, neuron cell-cell adhesion, axon, regulation of hormone levels, and regulation of secretion by cell. Of which, nine DEGs were furtherly selected as the HUB genes. Finally, CNTN4 and SH3GL2 were found to be highly expressed in malignant PCPGs and negatively correlated with progression-free interval. CONCLUSIONS: Malignant PCPGs tend to be aggressive in imaging and pathology. The high expression of CNTN4 and SH3GL2 in PCPGs may indicate a poor prognosis.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/genética , Feocromocitoma/patología , Pronóstico , Paraganglioma/genética , Neoplasias de las Glándulas Suprarrenales/patología
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