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1.
Cell ; 186(17): 3577-3592.e18, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37499659

RESUMEN

Hybrid sterility restricts the utilization of superior heterosis of indica-japonica inter-subspecific hybrids. In this study, we report the identification of RHS12, a major locus controlling male gamete sterility in indica-japonica hybrid rice. We show that RHS12 consists of two genes (iORF3/DUYAO and iORF4/JIEYAO) that confer preferential transmission of the RHS12-i type male gamete into the progeny, thereby forming a natural gene drive. DUYAO encodes a mitochondrion-targeted protein that interacts with OsCOX11 to trigger cytotoxicity and cell death, whereas JIEYAO encodes a protein that reroutes DUYAO to the autophagosome for degradation via direct physical interaction, thereby detoxifying DUYAO. Evolutionary trajectory analysis reveals that this system likely formed de novo in the AA genome Oryza clade and contributed to reproductive isolation (RI) between different lineages of rice. Our combined results provide mechanistic insights into the genetic basis of RI as well as insights for strategic designs of hybrid rice breeding.


Asunto(s)
Tecnología de Genética Dirigida , Oryza , Hibridación Genética , Oryza/genética , Fitomejoramiento/métodos , Aislamiento Reproductivo , Infertilidad Vegetal
2.
Proc Natl Acad Sci U S A ; 119(36): e2121671119, 2022 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-36037381

RESUMEN

Carbohydrate partitioning between the source and sink tissues plays an important role in regulating plant growth and development. However, the molecular mechanisms regulating this process remain poorly understood. In this study, we show that elevated auxin levels in the rice dao mutant cause increased accumulation of sucrose in the photosynthetic leaves but reduced sucrose content in the reproductive organs (particularly in the lodicules, anthers, and ovaries), leading to closed spikelets, indehiscent anthers, and parthenocarpic seeds. RNA sequencing analysis revealed that the expression of AUXIN RESPONSE FACTOR 18 (OsARF18) and OsARF2 is significantly up- and down-regulated, respectively, in the lodicule of dao mutant. Overexpression of OsARF18 or knocking out of OsARF2 phenocopies the dao mutant. We demonstrate that OsARF2 regulates the expression of OsSUT1 through direct binding to the sugar-responsive elements (SuREs) in the OsSUT1 promoter and that OsARF18 represses the expression of OsARF2 and OsSUT1 via direct binding to the auxin-responsive element (AuxRE) or SuRE in their promoters, respectively. Furthermore, overexpression of OsSUT1 in the dao and Osarf2 mutant backgrounds could largely rescue the spikelets' opening and seed-setting defects. Collectively, our results reveal an auxin signaling cascade regulating source-sink carbohydrate partitioning and reproductive organ development in rice.


Asunto(s)
Metabolismo de los Hidratos de Carbono , Flores , Ácidos Indolacéticos , Oryza , Flores/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Técnicas de Inactivación de Genes , Ácidos Indolacéticos/metabolismo , Mutación , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sacarosa/metabolismo
3.
Neuroimage ; 295: 120651, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38788914

RESUMEN

The functional connectivity (FC) graph of the brain has been widely recognized as a ``fingerprint'' that can be used to identify individuals from a group of subjects. Research has indicated that individual identification accuracy can be improved by eliminating the impact of shared information among individuals. However, current research extracts not only shared information of inter-subject but also individual-specific information from FC graphs, resulting in incomplete separation of shared information and fingerprint information among individuals, leading to lower individual identification accuracy across all functional magnetic resonance imaging (fMRI) states session pairs and poor cognitive behavior prediction performance. In this paper, we propose a method to enhance inter-subject variability combining conditional variational autoencoder (CVAE) network and sparse dictionary learning (SDL) module. By embedding fMRI state information in the encoding and decoding processes, the CVAE network can better capture and represent the common features among individuals and enhance inter-subject variability by residual. Our experimental results on Human Connectome Project (HCP) data show that the refined connectomes obtained by using CVAE with SDL can accurately distinguish an individual from the remaining participants. The success accuracies reached 99.7 % and 99.6 % in the session pair rest1-rest2 and reverse rest2-rest1, respectively. In the identification experiment involving task-task combinations carried out on the same day, the identification accuracies ranged from 94.2 % to 98.8 %. Furthermore, we showed the Frontoparietal and Default networks make the most significant contributions to individual identification and the edges that significantly contribute to individual identification are found within and between the Frontoparietal and Default networks. Additionally, high-level cognitive behaviors can also be better predicted with the obtained refined connectomes, suggesting that higher fingerprinting can be useful for resulting in higher behavioral associations. In summary, our proposed framework provides a promising approach to use functional connectivity networks for studying cognition and behavior, promoting a deeper understanding of brain functions.


Asunto(s)
Encéfalo , Cognición , Conectoma , Imagen por Resonancia Magnética , Humanos , Conectoma/métodos , Imagen por Resonancia Magnética/métodos , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Cognición/fisiología , Adulto , Red Nerviosa/fisiología , Red Nerviosa/diagnóstico por imagen , Masculino , Femenino
4.
Biomacromolecules ; 25(7): 4317-4328, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38829675

RESUMEN

Despite great progress in the hydrogel hemostats and dressings, they generally lack resistant vascular bursting pressure and intrinsic bioactivity to meet arterial massive hemorrhage and proheal wounds. To address the problems, we design a kind of biomimetic and wound microenvironment-modulating PEGylated glycopolypeptide hydrogels that can be easily injected and gelled in ∼10 s. Those glycopolypeptide hydrogels have suitable tissue adhesion of ∼20 kPa, high resistant bursting pressure of ∼150 mmHg, large microporosity of ∼15 µm, and excellent biocompatibility with ∼1% hemolysis ratio and negligible inflammation. They performed better hemostasis in rat liver and rat and rabbit femoral artery bleeding models than Fibrin glue, Gauze, and other hydrogels, achieving fast arterial hemostasis of <20 s and lower blood loss of 5-13%. As confirmed by in vivo wound healing, immunofluorescent imaging, and immunohistochemical and histological analyses, the mannose-modified hydrogels could highly boost the polarization of anti-inflammatory M2 phenotype and downregulate pro-inflammatory tumor necrosis factor-α to relieve inflammation, achieving complete full-thickness healing with thick dermis, dense hair follicles, and 90% collagen deposition. Importantly, this study provides a versatile strategy to construct biomimetic glycopolypeptide hydrogels that can not only resist vascular bursting pressure for arterial massive hemorrhage but also modulate inflammatory microenvironment for wound prohealing.


Asunto(s)
Hemorragia , Hidrogeles , Polietilenglicoles , Cicatrización de Heridas , Animales , Hidrogeles/química , Hidrogeles/farmacología , Ratas , Conejos , Polietilenglicoles/química , Polietilenglicoles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Hemorragia/tratamiento farmacológico , Ratas Sprague-Dawley , Masculino , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Glicopéptidos/química , Glicopéptidos/farmacología , Arteria Femoral/lesiones , Arteria Femoral/efectos de los fármacos
5.
Plant Cell Rep ; 43(2): 34, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38200377

RESUMEN

KEY MESSAGE: PbMYB1L enhances the cold tolerance and anthocyanin accumulation of transgenic Arabidopsis by regulating the expression of genes related to the cold-responsive genes pathway and anthocyanin synthesis pathway. MYB transcription factors (TFs) have been demonstrated to play diverse roles in plant growth and development. In the present study, we identified a novel R2R3-MYB transcription factor, PbMYB1L, from the peel of 'Red Zaosu' pear (Pyrus bretschneideri), which was induced by cold stress and acted as a positive regulator in anthocyanin biosynthesis. Notably, the transgenic Arabidopsis lines exhibited enhanced tolerance to cold stress. Compared to the Arabidopsis wild-type plants, the transgenic lines displayed longer primary roots and reduced reactive oxygen species (ROS) levels including O2-, hydrogen peroxide (H2O2), and malondialdehyde (MDA). Furthermore, significant upregulation of key cold-responsive genes AtCBF1, AtCBF2, AtCBF3, AtCBF4, and AtKIN1 was observed in the transgenic plants under cold stress conditions compared to wild type. Arabidopsis plants overexpressing PbMYB1L had significant anthocyanin accumulation in leaves after cold treatment with quantitative results indicating higher expression of anthocyanin structural genes compared to wild type. These findings suggest that PbMYB1L not only plays a vital role in conferring cold tolerance but also acts as a crucial regulator of anthocyanin biosynthesis.


Asunto(s)
Arabidopsis , Pyrus , Factores de Transcripción/genética , Pyrus/genética , Antocianinas , Arabidopsis/genética , Peróxido de Hidrógeno
6.
Sensors (Basel) ; 24(10)2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38793836

RESUMEN

The S-transform is a fundamental time-frequency (T-F) domain analysis method in ground penetrating radar (GPR) data processing and can be used for identifying targets, denoising, extracting thin layers, and high-resolution imaging. However, the S-transform spectrum experiences energy leakage near the instantaneous frequency. This phenomenon causes frequency components to erroneously spread over a wider range, impacting the accuracy and precision of GPR data processing. Synchrosqueezing is an effective method to prevent spectrum leakage. In this work, we introduce the synchrosqueezing generalized phase-shifting S-transform (SS-GPST). Initially, it resolves the compatibility issue between the S-transform and the synchrosqueezing strategy through phase-shifting. Subsequently, the SS-GPST accomplishes spectral energy focusing and resolution enhancement via a generalized parameter and synchrosqueezing. A synthetic signal test shows that the SS-GPST excels over other methods at focusing degree, spectral resolution, and signal reconstruction accuracy and speed. In actual GPR tunnel detection data processing, we assess the adaptability of the SS-GPST from three aspects: spectral energy distribution, thin layer identification, and data denoising. The results indicate: (1) compared to other methods, the SS-GPST accurately expresses spectral components with a strong focusing degree and fewer interference components; (2) high-frequency slices of the SS-GPST accurately detect the top and bottom interfaces of a 3.0-3.5 cm reinforcement protection layer; and (3) due to fewer interference components in the SS-GPST spectrum, reconstructing GPR profiles through the SS-GPST inverse transform is an efficient denoising technique. The SS-GPST demonstrates adaptability to different data processing purposes, offers high-resolution T-F spectra, and shows potential to supersede the S-transform.

7.
Oecologia ; 201(2): 575-584, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36688977

RESUMEN

Atmospheric nitrogen (N) deposition is altering grassland productivity and community structure worldwide. Deposited N comes in different forms, which can have different consequences for productivity due to differences in their fertilization and acidification effects. We hypothesize that these effects may be mediated by changes in plant functional traits. We investigated the responses of aboveground primary productivity and community functional composition to addition of three nitrogen compounds (NH4NO3, [NH4]2SO4, and CO[NH2]2) at the rates of 0, 5, 10, 20 g N m-2 yr-1. We used structural equation modeling (SEM) to evaluate how functional structure influences the responses of productivity to the three N compounds. Nitrogen addition increased community-level leaf chlorophyll content but decreased leaf dry matter content and phosphorus concentration. These changes were mainly due to intra-specific variation. Functional dispersion of traits was reduced by N addition through changes in species composition. SEM revealed that fertilization effects were more important than soil acidification for the responses of productivity to CO(NH2)2 addition, which enhanced productivity by decreasing functional trait dispersion. In contrast, the effects of (NH4)2SO4 and NH4NO3 were primarily due to soil acidification, influencing productivity via community-weighted means of functional traits. Our results suggest that N forms with different fertilizing and acidifying effects influence productivity via different functional traits pathways. Our study also emphasizes the need for in situ experiments with the relevant N compounds to accurately understand and predict the ecological effects of atmospheric N deposition on ecosystems.


Asunto(s)
Ecosistema , Compuestos de Nitrógeno , Pradera , Nitrógeno/metabolismo , Suelo/química
8.
J Appl Toxicol ; 43(4): 508-516, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36199206

RESUMEN

Vinpocetine injection is often used in clinical treatment of acute cardiovascular and cerebrovascular diseases. However, it was reported that vinpocetine injection caused allergic reactions in clinical use; therefore, its safety needs urgent attention. Until now, research on its sensitization is rarely reported. Here, the components contained in three vinpocetine injections were examined. It was found that besides vinpocetine, the synthetic raw material vincamine, the excipients benzyl alcohol and ethyl p-toluenesulfonate, and the impurities A, B, C, and D, which are excipients specified in the European Pharmacopoeia, were also present in them. Then the Mas-related G-protein-coupled receptor X2 (MRGPRX2)-HEK293 cell membrane chromatography was used to investigate the affinity of them with MRGPRX2 and found that vinpocetine, vincamine, and impurities A, B, C, and D bind to MRGPRX2. Afterwards, these compounds were further used to investigate the local sensitization ability in vivo. The results showed that vinpocetine, vincamine, and impurity C could induce swelling of the paw and decrease body temperature in mice, but only impurity C could cause local skin mast cell degranulation and serum histamine release increase. In vitro, the results also indicated that impurity C could increase intracellular [Ca2+ ] in MRGPRX2-HEK293 cells, whereas vinpocetine and vincamine did not. Therefore, the impurity C was the potential anaphylactoid component in vinpocetine injection, which may be one of the reasons for the occurrence of allergic reactions in the clinical use of vinpocetine injection. This work provides evidence on the sensitization of impurity C and also contributes to promoting the clinical safety of vinpocetine injection.


Asunto(s)
Anafilaxia , Vincamina , Humanos , Animales , Ratones , Células HEK293 , Anafilaxia/inducido químicamente , Vincamina/metabolismo , Vincamina/uso terapéutico , Excipientes , Receptores Acoplados a Proteínas G/metabolismo , Membrana Celular/metabolismo , Cromatografía , Mastocitos/metabolismo , Degranulación de la Célula , Proteínas del Tejido Nervioso/metabolismo , Receptores de Neuropéptido/metabolismo , Receptores de Neuropéptido/uso terapéutico
9.
J Appl Toxicol ; 43(8): 1130-1138, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36807361

RESUMEN

Under acidic and high temperature conditions, 5-hydroxymethylfurfural (5-HMF) converted from sugar further produces dimers (Compound II) and trimers (Compound III). The polymers were less reported, and sensitization effect of them was reported in this study. Compounds II and III induced the local and systemic anaphylaxis effect in passive cutaneous anaphylaxis mice model and activated RBL-2H3 cell inducing [Ca2+ ] mobilization, resulting in the release of ß-hexosaminidase and histamine in vitro. The gene knockdown assay figured out that Compounds II and III induced degranulation through FcεRI. Further, Compounds II and III had a certain affinity with FcεRI by cell membrane chromatography and may combine on the "proline sandwich" structure indicated by molecular docking. All above suggested Compounds II and III can induce pseudo-allergic reaction through FcεRI in vivo and in vitro. Our work provides basic research to prove that the newly discovered 5-HMF transformants, Compounds II and III, induce pseudo-allergic reaction in vitro and in vivo through FcεRI, which is different pathway from 5-HMF. In foods with high sugar content, the sensitization of Compounds II and III needs more attention. In high-sugar foods and medicines, especially traditional Chinese medicine injections, the content of transformants needs to be detected.


Asunto(s)
Anafilaxia , Furaldehído , Receptores de IgE , Animales , Ratones , Anafilaxia/inducido químicamente , Degranulación de la Célula , Mastocitos , Simulación del Acoplamiento Molecular , Receptores de IgE/genética , Receptores de IgE/metabolismo , Azúcares/metabolismo , Azúcares/farmacología
10.
Bioorg Med Chem Lett ; 59: 128575, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35065236

RESUMEN

Pseudo-allergic reactions frequently occur following clinical drug use and sometimes even cause mortal danger. Mas-related G-protein-coupled receptor member X2 (MRGPRX2) is a novel receptor that mediates pseudo-allergy and is an important target in the treatment of allergies. However, to date, there are no synthetic small-molecule inhibitors that prevent anaphylactoid reactions through this pathway. Our preliminary research suggested that B10-S and mubritinib effectively inhibited LAD2 cells. Therefore, two novel derivatives were synthesized by integrating the active substructures of B10-S and mubritinib, according to the molecular docking results. The antiallergic inhibitory effects of the two compounds were preliminarily evaluated in vitro using ß-hexosaminidase release, histamine release, and intracellular Ca2+ mobilization assays, and their binding sites on MRGPRX2 were analyzed by molecular docking. Both substances inhibited ß-hexosaminidase and histamine release in LAD2 cells and decreased intracellular Ca2+ by inhibiting MRGPRX2 in MRGPRX2-HEK293 cells treated with C48/80 in a dose-dependent manner. The docking results suggested that the molecules could competitively bind to the active site on MRGPRX2 and Glu141, which were combined by C48/80. Our study indicated that the two compounds have potential anti-allergic properties, which may provide evidence that will facilitate the development of synthetic molecules with anti-pseudo-allergic activity for clinical use in the future.


Asunto(s)
Anafilaxia/tratamiento farmacológico , Antialérgicos/farmacología , Hipersensibilidad/tratamiento farmacológico , Proteínas del Tejido Nervioso/metabolismo , Oxazoles/farmacología , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropéptido/metabolismo , Triazoles/farmacología , Anafilaxia/metabolismo , Antialérgicos/síntesis química , Antialérgicos/química , Línea Celular , Relación Dosis-Respuesta a Droga , Células HEK293 , Humanos , Hipersensibilidad/metabolismo , Estructura Molecular , Oxazoles/síntesis química , Oxazoles/química , Relación Estructura-Actividad , Triazoles/síntesis química , Triazoles/química
11.
Microb Pathog ; 156: 104929, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33932547

RESUMEN

Since the beginning of December 2019, a novel Coronavirus severe respiratory disease, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which also been termed 2019-new CoV (2019-nCoV), has continued to spread worldwide. As of August 27, 2020, a total of 24,232,429 people have been infected and 826,518 people have died. In our study, we found that astemizole can antagonize ACE2 and inhibit the entry of SARS-COV-2 spike pseudovirus into ACE2-expressed HEK293T cells (ACE2hi cells). We analysied the binding character of astemizole to ACE2 by molecular docking and surface plasmon resonance (SPR) assays and molecule docking, SARS-COV-2 spike pseudotype virus was also taken to investigate the suppression viropexis effect of astemizole. The results showed that astemizole can bind to the ACE2 receptor and inhibit the invasion of SARS-COV-2 Spike pseudoviruses. Thus astemizole represent potential drug candidates that can be re-used in anti-coronavirus therapies.


Asunto(s)
COVID-19 , Preparaciones Farmacéuticas , Astemizol/farmacología , Células HEK293 , Humanos , Simulación del Acoplamiento Molecular , Unión Proteica , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Internalización del Virus
12.
Immunopharmacol Immunotoxicol ; 43(1): 77-84, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33327824

RESUMEN

BACKGROUND: Clozapine is one of the most widely used second-generation antipsychotics in clinic. However, allergy-like symptoms such as rash and angioedema have been reported frequently, and the mechanism is still not clear. Mas-related G protein-coupled receptor X2 (MRGPRX2) expressed on mast cells is a crucial receptor for drug induced pseudo-allergic reactions. Therefore, we explored whether the symptoms induced by clozapine were associated with allergic reaction through MRGPRX2. METHODS: The effects of clozapine on pseudo-allergic reactions were evaluated by mast cells degranulation and calcium mobilization assay in vitro, and mice hindpaw swelling, serum histamine detection, avidin and H&E staining assay in vivo. The overexpressed MRGPRX2 cells membrane chromatography (MRGPRX2-HEK293/CMC), MRGPRX2-HEK293 cells calcium mobilization assay and molecular docking were applied to research the correlation between clozapine and MRGPRX2. RESULTS: The study showed that clozapine induced the release of ß-hexosaminidase, histamine and monocyte chemoattractant protein-1 (MCP-1), and trigged calcium mobilization in mast cells. In vivo, clozapine induced paw swelling, degranulation and vasodilation. Furthermore, clozapine could activate the calcium mobilization obviously in MRGPRX2-HEK293 cells, not in NC-HEK293 cells. Clozapine also had a good retention characteristic on MRGPRX2-HEK293/CMC column and the K D value is (2.33 ± 0.21)×10-01M. CONCLUSIONS: Our findings demonstrated that clozapine could induce pseudo-allergic reactions and MRGPRX2 might be the critical receptor for it.


Asunto(s)
Degranulación de la Célula/efectos de los fármacos , Clozapina/efectos adversos , Clozapina/metabolismo , Hipersensibilidad a las Drogas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropéptido/metabolismo , Animales , Calcio/metabolismo , Degranulación de la Célula/fisiología , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Antagonistas de la Serotonina/efectos adversos , Antagonistas de la Serotonina/metabolismo
13.
Plant Physiol ; 181(3): 1223-1238, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31515447

RESUMEN

In flowering plants, the tapetum cells in anthers undergo programmed cell death (PCD) at the late meiotic stage, providing nutrients for further development of microspores, including the formation of the pollen wall. However, the molecular basis of tapetum PCD remains elusive. Here we report a tapetum PCD-related mutant in rice (Oryza sativa), earlier degraded tapetum 1 (edt1), that shows complete pollen abortion associated with earlier-than-programmed tapetum cell death. EDT1 encodes a subunit of ATP-citrate lyase (ACL), and is specifically expressed in the tapetum of anthers. EDT1 localized in both the nucleus and the cytoplasm as observed in rice protoplast transient assays. We demonstrated that the A and B subunits of ACL interacted with each other and might function as a heteromultimer in the cytoplasm. EDT1 catalyzes the critical steps in cytosolic acetyl-CoA synthesis. Our data indicated a decrease in ATP level, energy charge, and fatty acid content in mutant edt1 anthers. In addition, the genes encoding secretory proteases or lipid transporters, and the transcription factors known to regulate PCD, were downregulated. Our results demonstrate that the timing of tapetum PCD must be tightly regulated for successful pollen development, and that EDT1 is involved in the tapetum PCD process. This study furthers our understanding of the molecular basis of pollen fertility and fecundity in rice and may also be relevant to other flowering plants.


Asunto(s)
ATP Citrato (pro-S)-Liasa/metabolismo , Oryza/citología , Oryza/enzimología , Proteínas de Plantas/metabolismo , ATP Citrato (pro-S)-Liasa/genética , Apoptosis/genética , Apoptosis/fisiología , Flores/citología , Flores/enzimología , Flores/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Oryza/metabolismo , Proteínas de Plantas/genética , Polen/citología , Polen/enzimología , Polen/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
14.
J Appl Clin Med Phys ; 20(8): 134-140, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31343821

RESUMEN

PURPOSE: This work aims to develop a knowledge-based automated dose volume histogram (DVH) prediction module that serves as a plan quality evaluation tool and treatment planning guidance in commercial Pinnacle3 treatment planning system (Philips Radiation Oncology Systems, Fitchburg, WI, USA). METHODS: The knowledge-based automated DVH prediction module was developed with kernel density estimation (KDE) method and applied for Pinnacle3 treatment planning system. Treatment plan data from 20 esophageal cancer cases were used for creating a module to predict DVHs. Twenty additional esophageal clinical plans were evaluated on the developed module. Predicted DVHs were compared with manual ones. Differences between the predicted and achieved DVHs were analyzed. RESULTS: The plan evaluation module was successfully implemented in Pinnacle3 treatment planning system. Strong linear correlations were found between predicted and achieved DVH for organs at risk. Suboptimal treatment plan quality could be improved according to the predicted DVHs by the module. CONCLUSION: The knowledge-based automated DVH prediction module implemented in Pinnacle3 could be used to efficiently evaluate the treatment plan quality and as guidance for further plan optimization.


Asunto(s)
Automatización , Neoplasias Esofágicas/radioterapia , Órganos en Riesgo/efectos de la radiación , Guías de Práctica Clínica como Asunto/normas , Garantía de la Calidad de Atención de Salud/normas , Planificación de la Radioterapia Asistida por Computador/normas , Programas Informáticos , Humanos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos
15.
Biochem Biophys Res Commun ; 498(3): 693-699, 2018 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-29524401

RESUMEN

Increasing prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide has necessitated a more thorough understanding of it and expanded the scope of research in this field. Women are more resistant to NAFLD than men despite equal exposure to major risk factors, such as obesity or hyperlipidemia. Female resistance is hormone-dependent, as evidenced by the sharp increase in NAFLD incidence in post-menopausal women who do not take hormone replacement therapy. Here, we found that the estrogen-responsive pituitary hormone prolactin (PRL), through specific PRL receptor (PRLR), down-regulates hepatic triglyceride (TG) accumulation. PRL was demonstrated to significantly down-regulate hepatic TG accumulation in female mice and protect male mice from liver steatosis induced by high-fat diet. Interestingly, Ad-shPRLR injected mice, whose hepatic PRLR abundance was effectively decreased at the protein levels, exhibited significantly aggravated liver steatosis. PRL could decrease the expression of stearoyl-coenzyme A desaturase 1 (SCD1), the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids, in animal models and multiple hepatic cell lines. Following knockdown of PRLR, the changes to PRL-triggered SCD1 expression disappeared. Thus, PRL acted as a previously unrecognized master regulator of liver TG metabolism, indicating that modification of PRL via PRLR might serve as a potential therapeutic target for NAFLD.


Asunto(s)
Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Receptores de Prolactina/metabolismo , Triglicéridos/metabolismo , Animales , Células Cultivadas , Dieta Alta en Grasa/efectos adversos , Femenino , Células Hep G2 , Humanos , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/patología , Prolactina/metabolismo , Interferencia de ARN , Receptores de Prolactina/genética , Estearoil-CoA Desaturasa/metabolismo
17.
Integr Zool ; 19(2): 183-199, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37231642

RESUMEN

Understanding the competition and coexistence of flagship carnivores is key to creating strategies for their conservation in the face of global carnivore declines. Although studies exploring the dynamics and competition between tigers (Panthera tigris) and leopards (P. pardus) span decades, there is a lack of understanding regarding the factors that influence their coexistence mechanisms on a broad scale, as well as the drivers determining their exploitative and interference competition. We gathered a comprehensive list of research papers among which 36 papers explored the interspecific interactions between tigers and leopards and tested the influence of biotic and abiotic factors on the coexistence mechanisms along three dimensions using multiple response variables regression models; we also tested the influence of ecological drivers determining the exploitative or interference competition between tigers and leopards. Elevation and ungulate density were the most important predictors in regulating the coexistence mechanisms. Tigers and leopards exhibited more positive relations/higher overlaps as elevation increased in the spatial niche. In addition, they showed a higher dietary overlap in the prey-rich regions. We determined that interference competition between tigers and leopards was less frequently observed in habitats with dense tree cover and homogeneous vegetation structures. Meanwhile, studies with multiple metrics would promote the detection of interference competition. Our study provides new insight into the competitive interactions and coexistence mechanisms of tigers and leopards on a broad scale. Policy-makers and managers should pay more attention to the factors of elevation, prey abundance, and habitat structures for the conservation of tigers and leopards.


Asunto(s)
Panthera , Animales , Asia , Simpatría , Árboles
18.
Adv Mater ; 36(5): e2307534, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38010259

RESUMEN

Perovskite photodetectors with bipolar photoresponse characteristics are expected to be applied in the field of secure optical communication (SOC). However, how to realize the perovskite photodetector with bipolar response remains challenging. Herein, by introducing bismuth iodide (BiI3 ) into Sn-Pb mixed perovskite precursor solution, 2D perovskite FA3 Bi2 I9 is spontaneously formed at the bottom to realize a wide-narrow bandgap-laminated perovskite film. Wavelength-dependent bipolar response is realized based on the absorption difference of the photoactive region with different bandgap combined with the carrier competition of the homotypic transport layer adopted in the as-fabricated photodetector. Under the visible/near-infrared (NIR) light irradiation, the bottom/top of the film generates a higher carrier concentration, where electrons are easier to be separated and transported by the SnO2 /PC61 BM to the bottom/top electrodes, respectively, resulting in a negative and positive bipolar response. Finally, based on positive NIR signal as the effective signal and negative visible signal as the interference signal, the SOC system is realized, where the positive NIR signal is well hidden by the negative visible signal. This work provides a simple and feasible strategy for fabrication of laminated perovskite films to achieve bipolar response.

19.
Chem Biol Drug Des ; 103(6): e14566, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38858134

RESUMEN

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic has triggered a significant impact on global public health security, it is urgent to develop effective antiviral drugs. Previous studies have found that binding to ACE2 is a key step in the invasion of SARS-CoV-2 into host cells, so virus invasion can be inhibited by blocking ACE2, but there are few reports on this kind of specific inhibitor. Our previous study found that Harringtonine (HT) can inhibit the entry of SARS-CoV-2 spike pseudovirus into ACE2h cells, but its relatively high cytotoxicity limits its further development. Amino acid modification of the active components can increase their solubility and reduce their cytotoxicity. Therefore, in this study, seven new derivatives were synthesized by amino acid modification of its core structure Cephalotaxine. The target compounds were evaluated by cell viability assay and the SARS-CoV-2 spike pseudovirus entry assay. Compound CET-1 significantly inhibited the entry of pseudovirus into ACE2h cells and showed less cytotoxicity than HT. Molecular docking results showed that CET-1 could bind TYR83, an important residue of ACE2, just like HT. In conclusion, our study provided a novel compound with more potential activity and lower toxicity than HT on inhibiting the SARS-CoV-2 spike pseudovirus infection, which makes it possible to be a lead compound as an antiviral drug in the future.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Antivirales , Tratamiento Farmacológico de COVID-19 , Homoharringtonina , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Aminoácidos/química , Aminoácidos/farmacología , Enzima Convertidora de Angiotensina 2/metabolismo , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Supervivencia Celular/efectos de los fármacos , COVID-19/virología , Homoharringtonina/farmacología , Homoharringtonina/química , SARS-CoV-2/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Glicoproteína de la Espiga del Coronavirus/química , Internalización del Virus/efectos de los fármacos , Harringtoninas/química , Harringtoninas/farmacología
20.
Foods ; 13(12)2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38928807

RESUMEN

Chamomile has become one of the world's most popular herbal teas due to its unique properties. Chamomile is widely used in dietary supplements, cosmetics, and herbal products. This study aimed to investigate the volatile aromatic components in chamomile. Two analytical techniques, gas chromatography-mass spectrometry (GC-MS) and an ultra-fast gas chromatography electronic nose, were employed to examine samples from Xinjiang (XJ), Shandong (SD), and Hebei (HB) in China, and imported samples from Germany (GER). The results revealed that all chamomile samples contained specific sesquiterpene compounds, including α-bisabolol, bisabolol oxide, bisabolone oxide, and chamazulene. Additionally, forty potential aroma components were identified by the electronic nose. The primary odor components of chamomile were characterized by fruity and spicy notes. The primary differences in the components of chamomile oil were identified as (E)-ß-farnesene, chamazulene, α-bisabolol oxide B, spathulenol and α-bisabolone oxide A. Significant differences in aroma compounds included geosmin, butanoic acid, 2-butene, norfuraneol, γ-terpinene. This study demonstrates that GC-MS and the ultra-fast gas chromatography electronic nose can preliminarily distinguish chamomile from different areas, providing a method and guidance for the selection of origin and sensory evaluation of chamomile. The current study is limited by the sample size and it provides preliminary conclusions. Future studies with a larger sample size are warranted to further improve these findings.

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