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1.
Animals (Basel) ; 14(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38731362

RESUMEN

This study investigated the efficacy of a composite probiotics composed of lactobacillus plantarum, lactobacillus reuteri, and bifidobacterium longum in alleviating oxidative stress in weaned piglets and pregnant sows. Evaluations of growth, oxidative stress, inflammation, intestinal barrier, and fecal microbiota were conducted. Results showed that the composite probiotic significantly promoted average daily gain in piglets (p < 0.05). It effectively attenuated inflammatory responses (p < 0.05) and oxidative stress (p < 0.05) while enhancing intestinal barrier function in piglets (p < 0.01). Fecal microbiota analysis revealed an increase in the abundance of beneficial bacteria such as faecalibacterium, parabacteroides, clostridium, blautia, and phascolarctobacterium in piglet feces and lactobacillus, parabacteroides, fibrobacter, and phascolarctobacterium in sow feces, with a decrease in harmful bacteria such as bacteroides and desulfovibrio in sow feces upon probiotic supplementation. Correlation analysis indicated significant negative associations of blautia with inflammation and oxidative stress in piglet feces, while treponema and coprococcus showed significant positive associations. In sow feces, lactobacillus, prevotella, treponema, and CF231 exhibited significant negative associations, while turicibacter showed a significant positive association. Therefore, the composite probiotic alleviated oxidative stress in weaned piglets and pregnant sows by modulating fecal microbiota composition.

2.
Brief Bioinform ; 25(3)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38647155

RESUMEN

Accurately delineating the connection between short nucleolar RNA (snoRNA) and disease is crucial for advancing disease detection and treatment. While traditional biological experimental methods are effective, they are labor-intensive, costly and lack scalability. With the ongoing progress in computer technology, an increasing number of deep learning techniques are being employed to predict snoRNA-disease associations. Nevertheless, the majority of these methods are black-box models, lacking interpretability and the capability to elucidate the snoRNA-disease association mechanism. In this study, we introduce IGCNSDA, an innovative and interpretable graph convolutional network (GCN) approach tailored for the efficient inference of snoRNA-disease associations. IGCNSDA leverages the GCN framework to extract node feature representations of snoRNAs and diseases from the bipartite snoRNA-disease graph. SnoRNAs with high similarity are more likely to be linked to analogous diseases, and vice versa. To facilitate this process, we introduce a subgraph generation algorithm that effectively groups similar snoRNAs and their associated diseases into cohesive subgraphs. Subsequently, we aggregate information from neighboring nodes within these subgraphs, iteratively updating the embeddings of snoRNAs and diseases. The experimental results demonstrate that IGCNSDA outperforms the most recent, highly relevant methods. Additionally, our interpretability analysis provides compelling evidence that IGCNSDA adeptly captures the underlying similarity between snoRNAs and diseases, thus affording researchers enhanced insights into the snoRNA-disease association mechanism. Furthermore, we present illustrative case studies that demonstrate the utility of IGCNSDA as a valuable tool for efficiently predicting potential snoRNA-disease associations. The dataset and source code for IGCNSDA are openly accessible at: https://github.com/altriavin/IGCNSDA.


Asunto(s)
ARN Nucleolar Pequeño , ARN Nucleolar Pequeño/genética , Humanos , Algoritmos , Biología Computacional/métodos , Redes Neurales de la Computación , Programas Informáticos , Aprendizaje Profundo
4.
J Biomed Opt ; 29(3): 036002, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38476220

RESUMEN

Significance: The conventional optical properties (OPs) reconstruction in spatial frequency domain (SFD) imaging, like the lookup table (LUT) method, causes OPs aliasing and yields only average OPs without depth resolution. Integrating SFD imaging with time-resolved (TR) measurements enhances space-TR information, enabling improved reconstruction of absorption (µa) and reduced scattering (µs') coefficients at various depths. Aim: To achieve the stratified reconstruction of OPs and the separation between µa and µs', using deep learning workflow based on the temporal and spatial information provided by time-domain SFD imaging technique, while enhancing the reconstruction accuracy. Approach: Two data processing methods are employed for the OPs reconstruction with TR-SFD imaging, one is full TR data, and the other is the featured data extracted from the full TR data (E, continuous-wave component, ⟨t⟩, mean time of flight). We compared their performance using a series of simulation and phantom validations. Results: Compared to the LUT approach, utilizing full TR, E and ⟨t⟩ datasets yield high-resolution OPs reconstruction results. Among the three datasets employed, full TR demonstrates the optimal accuracy. Conclusions: Utilizing the data obtained from SFD and TR measurement techniques allows for achieving high-resolution separation reconstruction of µa and µs' at different depths within 5 mm.


Asunto(s)
Aprendizaje Profundo , Diagnóstico por Imagen , Fantasmas de Imagen , Simulación por Computador
5.
Cell Commun Signal ; 22(1): 164, 2024 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448900

RESUMEN

Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXXmut, n = 7) or absence (MEN1/DAXXwild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease's progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.


Asunto(s)
Neoplasias Hepáticas , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Secuenciación del Exoma , Tumores Neuroendocrinos/genética , Genómica , Neoplasias Hepáticas/genética , Neoplasias Pancreáticas/genética , Microambiente Tumoral
6.
Opt Express ; 32(4): 6104-6120, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38439321

RESUMEN

We present a wide-field illumination time-domain (TD) diffusion optical tomography (DOT) for three-dimensional (3-D) reconstruction within a shallow region under the illuminated surface of the turbid medium. The methodological foundation is laid on the single-pixel spatial frequency domain (SFD) imaging that facilitates the adoption of the well-established time-correlated single-photon counting (TCSPC)-based TD detection and generalized pulse spectrum techniques (GPST)-based reconstruction. To ameliorate the defects of the conventional diffusion equation (DE) in the forward modeling of TD-SFD-DOT, mainly the low accuracy in the near-field region and in profiling early-photon migration, we propose a modified model employing the time-dependent δ-P1 approximation and verify its improved accuracy in comparison with both the Monte Carlo and DE-based ones. For a simplified inversion process, a modified GPST approach is extended to TD-SFD-DOT that enables the effective separation of the absorption and scattering coefficients using a steady-state equivalent strategy. Furthermore, we set up a single-pixel TD-SFD-DOT system that employs the TCSPC-based TD detection in the SFD imaging framework. For assessments of the reconstruction approach and the system performance, phantom experiments are performed for a series of scenarios. The results show the effectiveness of the proposed methodology for rapid 3-D reconstruction of the absorption and scattering coefficients within a depth range of about 5 mean free pathlengths.

7.
J Magn Reson Imaging ; 59(1): 297-308, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37165908

RESUMEN

BACKGROUND: Computed diffusion-weighted images (cDWI) of random b value could be derived from acquired DWI (aDWI) with at least two different b values. However, its comparison between aDWI and cDWI images in locally advanced rectal cancer (LARC) patients after neoadjuvant therapy (NT) is needed. PURPOSE: To compare the cDWI and aDWI in image quality, restaging, and treatment response of LARC after NT. STUDY TYPE: Retrospective. POPULATION: Eighty-seven consecutive patients. FIELD STRENGTH/SEQUENCE: 3.0 T/DWI. ASSESSMENT: All patients underwent two DWI sequences, including conventional acquisition with b = 0 and 1000 s/mm2 (aDWIb1000 ) and another with b = 0 and 700 s/mm2 on a 3.0-T MR scanner. The images of the latter were used to compute the diffusion images with b = 1000 s/mm2 (cDWIb1000 ). Four radiologists with 3, 4, 14, and 25 years of experience evaluated the images to compare the image quality, TN restaging performance, and treatment response between aDWIb1000 and cDWIb1000 . STATISTICAL TESTS: Interclass correlation coefficients, weighted κ coefficient, paired Wilcoxon, and McNemar or Fisher test were used. A significance level of 0.05 was used. RESULTS: The cDWIb1000 images were superior to the aDWIb1000 ones in both subjective and objective image quality. In T restaging, the overall diagnostic accuracy of cDWIb1000 images was higher than that of aDWIb1000 images (57.47% vs. 49.43%, P = 0.289 for the inexperienced radiologist; 77.01% vs. 63.22%, significant for the experienced radiologist), with better sensitivity in determining ypT0-Tis tumors. Additionally, it increased the sensitivity in detecting ypT2 tumors for the inexperienced radiologist and ypT3 tumors for the experienced radiologist. N restaging and treatment response were found to be similar between two sequences for both radiologists. DATA CONCLUSION: Compared to aDWIb1000 images, the computed ones might serve as a wise approach, providing comparable or better image quality, restaging performance, and treatment response assessment for LARC after NT. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.


Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Recto/patología
8.
J Chem Inf Model ; 63(18): 5936-5946, 2023 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-37674276

RESUMEN

The identification of drug sensitivity to mRNA interactions is crucial for drug development and disease treatment, but traditional experimental methods for verifying mRNA-drug sensitivity associations are labor-intensive and time-consuming. In this study, we present a hypergraph contrastive learning approach, HGCLMDA, to predict potential mRNA-drug sensitivity associations. HGCLMDA integrates a graph convolutional network-based method with a hypergraph convolutional network to mine high-order relationships between mRNA-drug association pairs. The proposed cross-view contrastive learning architecture improves the model's learning ability, and the inner product is used to obtain the mRNA-drug sensitivity association score. Our experiments on three mRNA-drug sensitivity association data sets show that HGCLMDA outperforms traditional graph convolutional network-based methods, graph augmentation-based contrastive learning methods, and state-of-the-art association prediction methods. The visualization experiment demonstrates the strong discrimination ability of the mRNA and drug embeddings learned by HGCLMDA, and experiments on sparse data sets showcase the performance and robustness of the method. In-depth analysis of hypergraph structures reveals a crucial role that hypergraphs play in enhancing the performance of models. The case study highlights the potential of HGCLMDA as a valuable tool for predicting mRNA-drug sensitivity associations. The interpretive analysis reveals that HGCLMDA effectively models the similarity between mRNA-mRNA and drug-drug interactions.


Asunto(s)
Desarrollo de Medicamentos , Aprendizaje , ARN Mensajero/genética , Proyectos de Investigación
9.
Cell Rep ; 42(8): 112892, 2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37516965

RESUMEN

Mammalian/mechanistic target of rapamycin (mTOR) regulates global protein synthesis through inactivation of eIF4E-binding proteins (m4E-BPs) in response to nutrient and energy availability. Until now, 4E-BPs have been considered as metazoan inventions, and how target of rapamycin (TOR) controls cap-dependent translation initiation in plants remains obscure. Here, we present short unstructured 4E-BP-like Arabidopsis proteins (4EBP1/4EBP2) that are non-homologous to m4E-BPs except for the eIF4E-binding motif and TOR phosphorylation sites. Unphosphorylated 4EBPs exhibit strong affinity toward eIF4Es and can inhibit formation of the cap-binding complex. Upon TOR activation, 4EBPs are phosphorylated, probably when bound directly to TOR, and likely relocated to ribosomes. 4EBPs can suppress a distinct set of mRNAs; 4EBP2 predominantly inhibits translation of core cell-cycle regulators CycB1;1 and CycD1;1, whereas 4EBP1 interferes with chlorophyll biosynthesis. Accordingly, 4EBP2 overexpression halts early seedling development, which is overcome by induction of Glc/Suc-TOR signaling. Thus, TOR regulates cap-dependent translation initiation by inactivating atypical 4EBPs in plants.


Asunto(s)
Factor 4E Eucariótico de Iniciación , Sirolimus , Animales , Sirolimus/farmacología , Factor 4E Eucariótico de Iniciación/genética , Factor 4E Eucariótico de Iniciación/metabolismo , Fosforilación , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Transducción de Señal , ARN Mensajero/metabolismo , Biosíntesis de Proteínas , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Mamíferos/metabolismo
11.
J Chem Phys ; 158(17)2023 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-37129143

RESUMEN

The absorption spectra of congenetic wurtzite (WZ) and zincblende (ZB) CdS magic-sized clusters are investigated. We demonstrate that the exciton peak positions can be tuned by up to 500 meV by varying the strong coupling between X-type ligands and the semiconductor cores, while the addition of L-type ligands primarily affects cluster midgap states. When Z-type ligands are displaced by L-type ligands, red shifts in the absorption spectra are observed, despite the fact there is a small decrease in cluster size. Density functional theory calculations are used to explain these findings and they reveal the importance of Cd and S dangling bonds on the midgap states during the Z- to L-type ligand exchange process. Overall, ZB CdS clusters show higher chemical stability than WZ clusters but their optical properties exhibit greater sensitivity to the solvent. Conversely, WZ CdS clusters are not stable in a Lewis base-rich environment, resulting in various changes in their spectra. Our findings enable researchers to select capping ligands that modulate the optical properties of semiconductor clusters while maintaining precise control over their solvent interactions.

12.
Plant J ; 2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37067011

RESUMEN

The nucleus is a central organelle of eukaryotic cells undergoing dynamic structural changes during cellular fundamental processes such as proliferation and differentiation. These changes rely on the integration of developmental and stress signals at the nuclear envelope (NE), orchestrating responses at the nucleo-cytoplasmic interface for efficient genomic functions such as DNA transcription, replication and repair. While in animals, correlation has already been established between NE dynamics and chromatin remodeling using last-generation tools and cutting-edge technologies, this topic is just emerging in plants, especially in response to mechanical cues. This review summarizes recent data obtained in this field with more emphasis on the mechanical stress response. It also highlights similarities/differences between animal and plant cells at multiples scales, from the structural organization of the nucleo-cytoplasmic continuum to the functional impacts of NE dynamics.

13.
Sci Rep ; 13(1): 2788, 2023 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-36797398

RESUMEN

Macrophage migration inhibitory factor (MIF) is an immune mediator associated with inflammation, which is upregulated after ischemia in brain tissue. ISO-1 is a potent inhibitor of MIF tautomerase and can protect neurons by reducing the permeability of blood brain barrier (BBB). In this study, we investigated the role of ISO-1 in cerebral ischemia/reperfusion injury by establishing a model of middle cerebral artery occlusion/reperfusion in rats. Rats were randomly divided into four groups: the sham operation group, the ISO-1group, the cerebral I/R group, and the ISO-1 + I/R group. We assessed the degree of neurological deficit in each group and measured the volume of cerebral infarction. We detected the expression of MIF in the core necrotic area and penumbra. We detected the expression of apoptosis-related proteins, apoptosis-inducing factor (AIF), endonuclease G (EndoG) and cytochrome c oxidase-IV (COX-IV) in the ischemic penumbra region. The results showed that MIF was expressed in the ischemic penumbra, while the injection of ISO-1 was able to alleviate neurological damage and reduce the infarction volume. In the cerebral ischemic penumbra region, ISO-1 could reduce the expression of Bax and Caspase3 and inhibit the displacement of AIF and EndoG to the nucleus simultaneously. Besides, ISO-1 also exhibited the ability to reduce apoptosis. In summary, ISO-1 may inhibit neuronal apoptosis through the endogenous mitochondrial pathway and reduce the injury of brain I/R after ischemic stroke.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Ratas , Animales , Ratas Sprague-Dawley , Isquemia Encefálica/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Apoptosis , Daño por Reperfusión/metabolismo
14.
J Exp Bot ; 74(5): 1420-1431, 2023 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-36515098

RESUMEN

Target of rapamycin (TOR) functions as a central sensory hub linking a wide range of external stimuli to gene expression. The mechanisms underlying stimulus-specific transcriptional reprogramming by TOR remain elusive. Here, we describe an in silico analysis in Arabidopsis demonstrating that TOR-repressed genes are associated with either bistable or silent chromatin states. Both states regulated by the TOR signaling pathway are associated with a high level of histone H3K27 trimethylation (H3K27me3) deposited by CURLY LEAF in a specific context with LIKE HETEROCHROMATIN PROTEIN1. The combination of the two epigenetic histone modifications H3K4me3 and H3K27me3 implicates a bistable feature that alternates between an 'on' and an 'off' state, allowing rapid transcriptional changes upon external stimuli. The chromatin remodeler SWI2/SNF2 ATPase BRAHMA activates TOR-repressed genes only at bistable chromatin domains to rapidly induce biotic stress responses. Here, we demonstrate both in silico and in vivo that TOR represses transcriptional stress responses through global maintenance of H3K27me3.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Histonas/genética , Histonas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cromatina/genética , Cromatina/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Ensamble y Desensamble de Cromatina , Regulación de la Expresión Génica de las Plantas , Fosfatidilinositol 3-Quinasas/genética
16.
Blood Press ; 32(1): 6-15, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-36495008

RESUMEN

PURPOSE: We investigated plasma angiotensin-converting enzyme 2 (ACE2) concentration in a population sample and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue in patients who underwent lung surgery. MATERIALS AND METHODS: The study participants were recruited from a residential area in the suburb of Shanghai for the plasma ACE2 concentration study (n = 503) and the lung tissue samples were randomly selected from the storage in Ruijin Hospital (80 men and 78 age-matched women). RESULTS: In analyses adjusted for covariables, men had a significantly higher plasma ACE2 concentration (1.21 vs. 0.98 ng/mL, p = 0.027) and the mean intensity of ACE2 in the lung tissue (55.1 vs. 53.9 a.u., p = 0.037) than women. With age increasing, plasma ACE2 concentration decreased (p = 0.001), while the mean intensity of ACE2 in the lung tissue tended to increase (p = 0.087). Plasma ACE2 concentration was higher in hypertension than normotension, especially treated hypertension (1.23 vs. 0.98 ng/mL, p = 0.029 vs. normotension), with no significant difference between users of RAS inhibitors and other classes of antihypertensive drugs (p = 0.64). There was no significance of the mean intensity of ACE2 in the lung tissue between patients taking and those not taking RAS inhibitors (p = 0.14). Neither plasma ACE2 concentration nor the mean intensity of ACE2 in the lung tissue differed between normoglycemia and diabetes (p ≥ 0.20). CONCLUSION: ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics of patients.Plain language summary What is the context? • The primary physiological function of ACE2 is the degradation of angiotensin I and II to angiotensin 1-9 and 1-7, respectively. • ACE2 was found to behave as a mediator of the severe acute respiratory syndrome coronavirus (SARS) infection. • There is little research on ACE2 in humans, especially in the lung tissue. • In the present report, we investigated plasma ACE2 concentration and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue respectively in two study populations. What is new? • Our study investigated both circulating and tissue ACE2 in human subjects. The main findings were: • In men as well as women, plasma ACE2 concentration was higher in younger than older participants, whereas the mean intensity of ACE2 in the lung tissue increase with age increasing. • Compared with normotension, hypertensive patients had higher plasma ACE2 concentration but similar mean intensity of ACE2 in the lung tissue. • Neither plasma ACE2 concentration nor lung tissue ACE2 expression significantly differed between users of RAS inhibitors and other classes of antihypertensive drugs. What is the impact? • ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics, such as sex, age, and treated and untreated hypertension. • A major implication is that plasma ACE2 concentration might not be an appropriate surrogate for the ACE2 expression in the lung tissue, and hence not a good predictor of SARS-COV-2 infection or fatality.


Asunto(s)
COVID-19 , Hipertensión , Masculino , Humanos , Femenino , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/farmacología , SARS-CoV-2/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Peptidil-Dipeptidasa A/farmacología , Antihipertensivos/farmacología , Sistema Renina-Angiotensina , China , Angiotensina I , Pulmón
17.
JMIR Serious Games ; 10(3): e36079, 2022 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-36094803

RESUMEN

BACKGROUND: With the advancements in the dental health care industry, the demand for dental technicians has increased. Dental technicians should be thoroughly assessed and trained in practical skills and pass professional certification examinations to ensure that they are competent to work closely with dentists. Unfortunately, such training courses and tests are in short supply worldwide. The use of virtual simulation technology can help solve these problems. OBJECTIVE: This study presents a new strategic framework design for a certified dental technician practical examination called as the certified Objective Manipulative Skill Examination of Dental Technicians (OMEDT), which is based on the Objective Structured Clinical Examination (OSCE). We present the development and validation of the OMEDT system, a new virtual simulated training system, to meet the demands of the OMEDT framework. The combination of OMEDT and the OMEDT system can solve the complex problems encountered in the certified dental technician practical examination with excellent efficiency, high quality, and low cost. METHODS: The OMEDT framework design was constructed according to the OSCE guide and the Chinese vocational skill standards for dental technicians. To develop the OMEDT system, we organized a new framework based on the virtual learning network platform, the haptic feedback system, and the real-time dental training and evaluation system. The effectiveness evaluation of the OMEDT system was divided into 2 phases: in the first phase, 36 students were recruited to use the test module to finish the task and their performance data were collected and analyzed; and in the second phase, a questionnaire was administered to 30 students who used the system for their studies and graduation exams. RESULTS: The OMEDT and the corresponding skill training virtual simulation OMEDT system were developed, and preliminary user evaluation was performed to assess their effectiveness and usefulness. The OMEDT system was found to improve students' practical skills by training with the evaluation results. In addition, several key research topics were explored, including the effects of positive feedback of the knowledge of results on the improvement of the students' skill level and the common sense transformation of educators in the virtual simulation technology environment. CONCLUSIONS: The development of OMEDT and the OMEDT system has been completed and their effectiveness has been verified.

18.
Plant Cell ; 34(10): 3814-3829, 2022 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-35792878

RESUMEN

Plants, unlike animals, respond to environmental challenges with comprehensive developmental transitions that allow them to cope with these stresses. Here we discovered that antagonistic activation of the Target of Rapamycin (TOR) kinase in Arabidopsis thaliana roots and shoots is essential for the nutrient deprivation-induced increase in the root-to-shoot ratio to improve foraging for mineral ions. We demonstrate that sulfate limitation-induced downregulation of TOR in shoots activates autophagy, resulting in enhanced carbon allocation to the root. The allocation of carbon to the roots is facilitated by the specific upregulation of the sucrose-transporter genes SWEET11/12 in shoots. SWEET11/12 activation is indispensable for enabling sucrose to act as a carbon source for growth and as a signal for tuning root apical meristem activity via glucose-TOR signaling. The sugar-stimulated TOR activity in the root suppresses autophagy and maintains root apical meristem activity to support root growth to enhance mining for new sulfate resources in the soil. We provide direct evidence that the organ-specific regulation of autophagy is essential for the increased root-to-shoot ratio in response to sulfur limitation. These findings uncover how sulfur limitation controls the central sensor kinase TOR to enable nutrient recycling for stress-induced morphological adaptation of the plant body.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Autofagia/genética , Carbono , Regulación de la Expresión Génica de las Plantas/genética , Glucosa , Proteínas de Transporte de Membrana , Meristema/metabolismo , Nutrientes , Fosfatidilinositol 3-Quinasas , Raíces de Plantas/metabolismo , Sirolimus , Suelo , Sacarosa , Sulfatos , Azufre , Serina-Treonina Quinasas TOR/metabolismo
19.
Ann Diagn Pathol ; 60: 152007, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35841867

RESUMEN

GATA3 has been reported to be positive in clear cell papillary renal cell carcinoma and papillary renal neoplasm with reverse polarity. However, its features in high-grade RCC remain unclear. Despite the emergence of novel renal entities, FH-deficient RCC remains one of the most aggressive renal neoplasms. The diagnosis is mainly based on the loss of FH at the protein level. Previous studies have shown that inclusion-like nuclei, multiple architectural patterns, FH loss, and 2SC positivity can differentiate FH-deficient RCC from other RCC. In some FH-deficient RCC cases, FH is normally expressed and is difficult to diagnose. This study included 11 FH-deficient RCC, and GATA3 showed different expression in seven cases. However, 147 papillary renal cell carcinomas were included, and GATA3 expression was negative. A comparison of clinicopathological aspects between 11 FH-deficient RCC and 30 high-grade PRCC showed statistical significance in age, size, multiple architectural patterns, inclusion-like nuclei, and prognosis. However, PRCC exhibited similar characteristics. CK7, GATA3, and FH profiles were also statistically significant. Different chromosomal alterations were found in FH-deficient RCC, and chromosomal alterations were not different between FH-deficient RCC and PRCC. GATA3 was positive in 33 % (7/21) of collecting duct carcinomas and negative in other high-grade renal neoplasms. GATA3 is negative in PRCC, but can be positive in FH-deficient RCC and collecting duct carcinoma. GATA3 expression may indicate a worse outcome in high-grade RCC with papillary architecture. We recommend GATA3 IHC for the differential diagnosis and prognostic assessment of high-grade RCC with papillary architecture.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/patología , Fumarato Hidratasa , Factor de Transcripción GATA3 , Humanos , Inmunohistoquímica , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Pronóstico
20.
Hum Pathol ; 127: 78-85, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35724772

RESUMEN

Papillary renal neoplasm with reverse polarity (PRNRP) is a newly documented renal entity with an easily recognizable morphology, distinct immunohistochemical profiles, and frequent KRAS mutations. The latest practice guidelines regard PRNRP as a subtype of papillary renal cell carcinoma due to the documented chromosomal alterations of 7, 17, and Y. This study included 20 patients with PRNRP and 30 patients with PRCC. Statistically significant differences were observed in size, WHO/ISUP grade, macrophages in the papillae, reverse polarity, CK7, basolateral positivity for Claudin7, GATA3 expression, KRAS mutation, and chromosomal alterations. No adverse events such as perinephric invasion, lymphovascular invasion, sarcomatoid of rhabdoid differentiation, metastasis, or recurrence were found in PRNRP. However, PRCC can cause these adverse events. Basolateral positivity for Claudin7 together with GATA3 expression indicated distal tubule derivation of PRNRP. KRAS mutations were detected in 89% (16/18) of PRNRP. No KRAS mutations were detected in PRCC. Six patients with PRNRP had one chromosomal alteration and the other 12 had no chromosomal alterations. However, only four patients with PRCC showed no chromosomal alterations. Eighteen patients had two or three chromosomal alterations. PRCC can metastasize, recur, and even cause death, whereas PRNRP has a favorable prognosis. We recommend that PRNRP should be separated from PRCC and partial nephrectomy is more suitable for PRNRP.


Asunto(s)
Carcinoma Papilar , Carcinoma de Células Renales , Neoplasias Renales , Carcinoma Papilar/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Aberraciones Cromosómicas , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Nefrectomía , Pronóstico
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