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Nickel (Ni) and copper (Cu) contamination have become major threats to plant survival worldwide. 24-epibrassinolide (24-EBR) and melatonin (MT) have emerged as valuable treatments to alleviate heavy metal-induced phytotoxicity. However, plants have not fully demonstrated the potential mechanisms by which these two hormones act under Ni and Cu stress. Herein, this study investigated the impact of individual and combined application of 24-EBR and MT on the growth and physiological traits of Primula forbesii Franch. subjected to stress (200 µmol L-1 Ni and Cu). The experiments compared the effects of different mitigation treatments on heavy metal (HM) stress and the scientific basis and practical reference for using these exogenous substances to improve HM resistance of P. forbesii in polluted environments. Nickel and Cu stress significantly hindered leaf photosynthesis and nutrient uptake, reducing plant growth and gas exchange. However, 24-EBR, MT, and 24-EBR + MT treatments alleviated the growth inhibition caused by Ni and Cu stress, improved the growth indexes of P. forbesii, and increased the gas exchange parameters. Exogenous MT effectively alleviated Ni stress, and 24-EBR + MT significantly alleviated the toxic effects of Cu stress. Unlike HM stress, MT and 24-EBR + MT activated the antioxidant enzyme activity (by increasing superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)), significantly reduced reactive oxygen species (ROS) accumulation, and regulated ascorbate and glutathione cycle (AsA-GSH) efficiency. Besides, the treatments enhanced the ability of P. forbesii to accumulate HMs, shielding plants from harm. These findings conclusively illustrate the capability of 24-EBR and MT to significantly bolster the tolerance of P. forbesii to Ni and Cu stress.
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Brassinosteroides , Cobre , Melatonina , Níquel , Esteroides Heterocíclicos , Brassinosteroides/farmacologia , Brassinosteroides/metabolismo , Melatonina/farmacologia , Melatonina/metabolismo , Esteroides Heterocíclicos/farmacologia , Níquel/toxicidade , Cobre/toxicidade , Fotossíntese/efeitos dos fármacos , Poluentes do Solo/toxicidade , Estresse Fisiológico/efeitos dos fármacos , Antioxidantes/metabolismo , Antioxidantes/farmacologiaRESUMO
Our study utilized 374 geographical distribution records of H. mutabilis and 19 bioclimatic factors, employing the MaxEnt model and the Geographic Information System (ArcGIS). The key environmental variables influencing the suitable distribution areas of H. mutabilis were analyzed through the comprehensive contribution rate, permutation importance, and Pearson correlation coefficient. Based on this analysis, the contemporary and future suitable distribution areas and their extents were predicted. The results indicate that the key limiting factor affecting the suitable distribution areas of H. mutabilis is the precipitation of the driest month (bio14), with secondary factors being annual precipitation (bio12), annual mean temperature (bio1), and annual temperature range (bio7). Under contemporary climate conditions, the total suitable area for H. mutabilis is approximately 2,076,600 km2, primarily concentrated in the tropical and subtropical regions of southeastern China. Under low-to-medium-emission scenarios (SSP1-2.6, SSP2-4.5), the total suitable area of H. mutabilis shows a trend of first decreasing and then increasing compared to the current scenario. In contrast, under high-emission scenarios (SSP5-8.5), it exhibits a trend of first increasing and then decreasing. The spatial pattern changes indicate that the retention rate of suitable areas for H. mutabilis ranges from 95.28% to 99.28%, with the distribution centers primarily located in Hunan and Guizhou provinces, showing an overall migration trend towards the west and north. These findings suggest that H. mutabilis possesses a certain level of adaptability to climate change. However, it is crucial to consider regional drought and sudden drought events in practical cultivation and introduction processes. The results of our study provide a scientific basis for the rational cultivation management, conservation, and utilization of germplasm resources of H. mutabilis.
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Alcea rosea L. is a traditional flower with a long cultivation history. It is extensively cultivated in China and is widely planted in green belt parks or used as cut flowers and potted ornamental because of its rich colors and flower shapes. Double-petal A. rosea flowers have a higher aesthetic value compared to single-petal flowers, a phenomenon determined by stamen petaloid. However, the underlying molecular mechanism of this phenomenon is still very unclear. In this study, an RNA-based comparative transcriptomic analysis was performed between the normal petal and stamen petaloid petal of A. rosea. A total of 3,212 differential expressed genes (DEGs), including 2,620 up-regulated DEGs and 592 down-regulated DEGs, were identified from 206,188 unigenes. Numerous DEGs associated with stamen petaloid were identified through GO and KEGG enrichment analysis. Notably, there were 63 DEGs involved in the plant hormone synthesis and signal transduction, including auxin, cytokinin, gibberellin, abscisic acid, ethylene, brassinosteroid, jasmonic acid, and salicylic acid signaling pathway and 56 key transcription factors (TFs), such as MADS-box, bHLH, GRAS, and HSF. The identification of these DEGs provides an important clue for studying the regulation pathway and mechanism of stamen petaloid formation in A. rosea and provides valuable information for molecular plant breeding.
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Flores , Perfilação da Expressão Gênica , Flores/genética , Flores/crescimento & desenvolvimento , Flores/anatomia & histologia , Transcriptoma , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Reguladores de Crescimento de Plantas/metabolismoRESUMO
GaN on Si plays an important role in the integration and promotion of GaN-based wide-gap materials with Si-based integrated circuits (IC) technology. A series of GaN film materials were grown on Si (111) substrate using a unique plasma assistant molecular beam epitaxy (PA-MBE) technology and investigated using multiple characterization techniques of Nomarski microscopy (NM), high-resolution X-ray diffraction (HR-XRD), variable angular spectroscopic ellipsometry (VASE), Raman scattering, photoluminescence (PL), and synchrotron radiation (SR) near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. NM confirmed crack-free wurtzite (w-) GaN thin films in a large range of 180-1500 nm. XRD identified the w- single crystalline structure for these GaN films with the orientation along the c-axis in the normal growth direction. An optimized 700 °C growth temperature, plus other corresponding parameters, was obtained for the PA-MBE growth of GaN on Si, exhibiting strong PL emission, narrow/strong Raman phonon modes, XRD w-GaN peaks, and high crystalline perfection. VASE studies identified this set of MBE-grown GaN/Si as having very low Urbach energy of about 18 meV. UV (325 nm)-excited Raman spectra of GaN/Si samples exhibited the GaN E2(low) and E2(high) phonon modes clearly without Raman features from the Si substrate, overcoming the difficulties from visible (532 nm) Raman measurements with strong Si Raman features overwhelming the GaN signals. The combined UV excitation Raman-PL spectra revealed multiple LO phonons spread over the GaN fundamental band edge emission PL band due to the outgoing resonance effect. Calculation of the UV Raman spectra determined the carrier concentrations with excellent values. Angular-dependent NEXAFS on Ga K-edge revealed the significant anisotropy of the conduction band of w-GaN and identified the NEXAFS resonances corresponding to different final states in the hexagonal GaN films on Si. Comparative GaN material properties are investigated in depth.
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Small molecular heat shock proteins (sHSPs) belong to the HSP family of molecular chaperones. Under high-temperature stress, they can prevent the aggregation of irreversible proteins and maintain the folding of denatured proteins to enhance heat resistance. In this study, the CmHSP17.9-1 and CmHSP17.9-2 genes, which were cloned from chrysanthemum (Chrysanthemum×morifolium 'Jinba') by homologous cloning, had a complete open reading frame of 480 bp each, encoding 159 amino acids. The protein subcellular localization analysis showed that CmHSP17.9-1 and CmHSP17.9-2 were located in the cytoplasm and mostly aggregated in granules, especially around the nucleus. Real-time quantitative PCR (qRT-PCR) analysis showed that the relative expression level of the CmHSP17.9-1 and CmHSP17.9-2 genes was highest in the terminal buds of the chrysanthemum, followed by the leaves. CmHSP17.9-1 and CmHSP17.9-2 overex-pression vectors were constructed and used to transform the chrysanthemum; overexpression of these genes led to the chrysanthemum phenotypes being less affected by high-temperature, and the antioxidant capacity was enhanced. The results showed that chrysanthemum with overex-pression of the CmHSP17.9-1 and CmHSP17.9-2 genes had stronger tolerance than the wild type chrysanthemum after high-temperature treatment or some degree of heat exercise, and overex-pression of the CmHSP17.9-1 gene led to stronger heat resistance than that of the CmHSP17.9-2 gene, providing an important theoretical basis for the subsequent molecular breeding and pro-duction applications of chrysanthemum.
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Chrysanthemum , Regulação da Expressão Gênica de Plantas , Proteínas de Choque Térmico Pequenas , Proteínas de Plantas , Sequência de Aminoácidos , Chrysanthemum/genética , Clonagem Molecular , Proteínas de Choque Térmico Pequenas/genética , Proteínas de Choque Térmico Pequenas/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genéticaRESUMO
Compound pollution with cadmium (Cd) and zinc (Zn) is common in nature. The effects of compounded Cd and Zn on the growth and development of Iris pseudacorus in the environment and the plant's potential to remediate heavy metals in the environment remain unclear. In this study, the effects of single and combined Cd and Zn stress on I. pseudacorus growth and the enrichment of heavy metals in I. pseudacorus seedlings were investigated. The results showed that under Cd (160⯵M) and Zn (800⯵M) stress, plant growth was significantly inhibited and photosynthetic performance was affected. Cd+Zn200 (160⯵M + 200⯵M) reduced the levels of malondialdehyde, hydrogen peroxide, and non-protein thiols by 31.29%, 53.20%, and 13.29%, respectively, in the aboveground tissues compared with levels in the single Cd treatment. However, Cd+Zn800 (160⯵M + 800⯵M) had no effect. Cd and Zn800 inhibited the absorption of mineral elements, while Zn200 had little effect on plants. Compared with that for Cd treatment alone, Cd + Zn200 and Cd+Zn800 reduced the Cd content in aboveground tissues by 54.15% and 49.92%, respectively, but had no significant effect on Cd in the root system. Zn significantly reduced the Cd content in subcellular components and limited the content and proportion of Cd extracted using water and ethanol. These results suggest that a low supply of Zn reduces Cd accumulation in aboveground tissues by promoting antioxidant substances and heavy metal chelating agents, thus protecting the photosynthetic systems. The addition of Zn also reduced the mobility and bioavailability of Cd to alleviate its toxicity in I. pseudacorus.
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Gênero Iris , Metais Pesados , Poluentes do Solo , Cádmio/toxicidade , Cádmio/análise , Zinco/toxicidade , Desenvolvimento Vegetal , Poluentes do Solo/toxicidadeRESUMO
The cotton rose (Hibiscus mutabilis) is a plant species commonly found in tropical and subtropical regions. It is remarkably resilient to waterlogging stress; however, the underlying mechanism behind this trait is yet unknown. This study used hypoxia-tolerant "Danbanhong" (DBH) and more hypoxia-sensitive "Yurui" (YR) genotypes and compared their morpho-physiological and transcriptional responses to hypoxic conditions. Notably, DBH had a higher number of adventitious roots (20.3) compared to YR (10.0), with longer adventitious roots in DBH (18.3 cm) than in YR (11.2 cm). Furthermore, the formation of aerenchyma was 3-fold greater in DBH compared to YR. Transcriptomic analysis revealed that DBH had more rapid transcriptional responses to hypoxia than YR. Identification of a greater number of differentially expressed genes (DEGs) for aerenchyma, adventitious root formation and development, and energy metabolism in DBH supported that DBH had better morphological and transcriptional adaptation than YR. DEG functional enrichment analysis indicated the involvement of variety-specific biological processes in adaption to hypoxia. Plant hormone signaling transduction, MAPK signaling pathway and carbon metabolism played more pronounced roles in DBH, whereas the ribosome genes were specifically induced in YR. These results show that effective multilevel coordination of adventitious root development and aerenchyma, in conjunction with plant hormone signaling and carbon metabolism, is required for increased hypoxia tolerance. This study provides new insights into the characterization of morpho-physiological and transcriptional responses to hypoxia in H. mutabilis, shedding light on the molecular mechanisms of its adaptation to hypoxic environments.
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Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Transcriptoma/genética , Adaptação Fisiológica/genética , Genótipo , Reguladores de Crescimento de Plantas/metabolismo , Estresse Fisiológico/genéticaRESUMO
OBJECTIVE: Long non-coding RNA (lncRNA), especially RNA associated with lymph node metastasis, plays an important role in the development of cancer. Identifying metastasis related lncRNAs and exploring their clinical significance can guide the treatment and prognosis of thyroid cancer patients. METHODS: RNA expression and clinical data of thyroid cancer was derived from The Cancer Genome Atlas (TCGA) database, while the survival data was obtained from the ULCAN database. R language and SPSS software were used to analyze the correlation between lncRNA and lymph node metastasis of thyroid cancer and the lncRNAs associated with lymph node metastasis were screened. RESULT: 10 lncRNAs showed significant differential expression in thyroid cancer with and without lymph node metastasis. Four lncRNAs (LRRC52-AS1, AP002358.1, AC004847.1, and AC254633.1) were overexpressed in metastatic thyroid cancer, while six lncRNAs (SLC26A4-AS1, LINC01886, LINC01789, AF131216.3, AC062015.1, and AL031710.1) were underexpressed. The expression levels of these lncRNAs were associated with the clinical staging of tumors. Cox regression analysis further showed that elevated expression levels of AP002358.1 and LRRC52-AS1 were associated with poor prognosis in patients with thyroid cancer. In addition, analysis of the UALCAN database indicated that these two lncRNAs were significantly overexpressed in thyroid cancer compared to other cancers, and the expression levels of AF131216.3 and AL031710.1 were associated with progression-free survival in thyroid cancer patients. CONCLUSION: These lncRNAs may play crucial roles in the development and progression of thyroid cancer and could serve as potential markers for predicting tumor metastasis, clinical stage, and patient prognosis.
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MicroRNAs , RNA Longo não Codificante , Neoplasias da Glândula Tireoide , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Metástase Linfática/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , MicroRNAs/genética , Prognóstico , Regulação Neoplásica da Expressão Gênica/genéticaRESUMO
BACKGROUND: Acute kidney injury (AKI), characterized by necroptosis and activation of MAPK pathway, causes sudden declines in renal function. To date, efficacious treatments are lacking. JianPiYiShen Formula (JPYSF) has a protective effect on the kidneys. The aim of this study is to explore the mechanism of JPYSF in cisplatin-induced AKI. METHODS: Male C57/BL6J mice were divided into control group, cisplatin group and cisplatin + JPYSF group. Before establishing the model, the cisplatin + JPYSF group was administered JPYSF (18.35 g/kg/day) by gavage for 5 consecutive days. A single intraperitoneal injection of cisplatin (20 mg/kg) was used to establish AKI model. Measurement of renal function and H&E staining were performed to assess renal damage. WB, PCR, TUNEL staining and immunohistochemistry were used to detect related indicators of mitochondrial function, oxidative stress, necroptosis, inflammation and MAPK pathway. And one-way analysis of variance was used to compare group differences. RESULTS: Compared with the cisplatin group, JPYSF can attenuate AKI, reflected by the decrease in Scr and BUN levels, the improvement of renal tubular injury, and the downregulation of NGAL and KIM1. Cisplatin can induce mitochondrial dysfunction and oxidative stress, triggering necroptosis. In this study, JPYSF improved mitochondrial dysfunction to enhance oxidative stress, as manifested by upregulation of OPA1, PGC-1α, SOD and CAT, and downregulation of DRP1 and MFF. Then JPYSF showed a significant protective effect in necroptosis, as embodied by reduced number of TUNEL-positive cells, decreased the gene expression of RIPK3 and MLKL, as well as downregulation the proteins expression of P-RIPK1, P-RIPK3, and P-MLKL. Moreover, necroptosis can aggravate inflammation. JPYSF ameliorated inflammation by improving inflammatory and anti-inflammatory indexes, including downregulation of TNF-α, IL-6, MCP-1 and LY6G, and upregulation of IL-10. In addition, JPYSF also inhibited MAPK pathway to improve necroptosis by decreasing the expression of P-JNK and P-ERK. CONCLUSION: Our data showed that JPYSF prevents cisplatin-induced AKI by improving necroptosis through MAPK pathway, which is related to the improvement of mitochondrial dysfunction, oxidative stress, and inflammation.
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Injúria Renal Aguda , Doenças Mitocondriais , Masculino , Camundongos , Animais , Cisplatino/efeitos adversos , Necroptose , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , InflamaçãoRESUMO
Methyl jasmonate (MeJA), a crucial phytohormone, which plays an important role in resistance to Cadmium (Cd) stress. The cell wall (CW) of root system is the main location of Cd and plays a key role in resistance to Cd toxicity. However, the mechanism effect of MeJA on the CW composition and Cd accumulation remain unclear. In this study, the contribution of MeJA in regulating CW structure, pectin composition and Cd accumulation was investigated in Cosmos bipinnatus. Phenotypic results affirm MeJA's significant role in reducing Cd-induced toxicity in C. bipinnatus. Notably, MeJA exerts a dual impact, reducing Cd uptake in roots while increasing Cd accumulation in the CW, particularly bound to pectin. The molecular structure of pectin, mainly uronic acid (UA), correlates positively with Cd content, consistent in HC1 and cellulose, emphasizing UA as pivotal for Cd binding. Furthermore, MeJA modulates pectin methylesterase (PME) activity under Cd stress, influencing pectin's molecular structure and homogalacturonan (HG) content affecting Cd-binding capacity. Chelate-soluble pectin (CSP) within soluble pectins accumulates a substantial Cd proportion, with MeJA regulating both UA content and the minor component 3-deoxy-oct-2-ulosonic acid (Kdo) in CSP. The study delves into the intricate regulation of pectin monosaccharide composition under Cd stress, revealing insights into the CW's physical defense and Cd binding. In summary, this research provides novel insights into MeJA-specific mechanisms alleviating Cd toxicity in C. bipinnatus, shedding light on complex interactions between MeJA, and Cd accumulation in CW pectin polysaccharide.
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Acetatos , Asteraceae , Cádmio , Ciclopentanos , Oxilipinas , Cádmio/metabolismo , Raízes de Plantas/metabolismo , Polissacarídeos/metabolismo , Polissacarídeos/farmacologia , Pectinas/química , Parede Celular/metabolismo , Asteraceae/metabolismoRESUMO
Low temperatures can severely affect plant growth and reduce their ornamental value. A family of plant histone deacetylases allows plants to cope with both biotic and abiotic stresses. In this study, we screened and cloned the cDNA of DgSRT2 obtained from transcriptome sequencing of chrysanthemum leaves under low-temperature stress. Sequence analysis showed that DgSRT2 belongs to the sirtuin family of histone deacetylases. We obtained the stable transgenic chrysanthemum lines OE-2 and OE-12. DgSRT2 showed tissue specificity in wild-type chrysanthemum and was most highly expressed in leaves. Under low-temperature stress, the OE lines showed higher survival rates, proline content, solute content, and antioxidant enzyme activities, and lower relative electrolyte leakage, malondialdehyde, hydrogen peroxide, and superoxide ion accumulation than the wild-type lines. This work suggests that DgSRT2 can serve as an essential gene for enhancing cold resistance in plants. In addition, a series of cold-responsive genes in the OE line were compared with WT. The results showed that DgSRT2 exerted a positive regulatory effect by up-regulating the transcript levels of cold-responsive genes. The above genes help to increase antioxidant activity, maintain membrane stability and improve osmoregulation, thereby enhancing survival under cold stress. It can be concluded from the above work that DgSRT2 enhances chrysanthemum tolerance to low temperatures by scavenging the ROS system.
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Chrysanthemum , Espécies Reativas de Oxigênio , Temperatura , Chrysanthemum/genética , Superóxidos/metabolismo , Estresse Fisiológico/genética , Resposta ao Choque Frio , Plantas Geneticamente Modificadas/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
BACKGROUND: Patients with differentiated thyroid cancer (DTC) usually have an excellent prognosis; however, 5 %-15 % develop radioactive iodine-refractory (RAIR) DTC (RAIR-DTC), which has a poor prognosis and limited treatment options. The aim of the present study was to investigate the clinicopathological characteristics of RAIR-DTC in order to provide clinical evidence for timely prediction of the effects of iodine therapy. METHODS: Clinicopathological data for 44 patients with RAIR-DTC and 50 patients with radioiodine-avid DTC (RAIA-DTC) were retrospectively analyzed. The risk factors for RAIR-DTC were evaluated and a RAIR-DTC prediction model was established. RESULTS: RAIR-DTC showed unique clinicopathological features that differed from those of RAIA-DTC; these included age >55 years, a high-risk histological subtype, a large tumor size, a late TNM stage, calcification, distant metastasis, and more than six metastatic lymph nodes. Patients with RAIR-DTC also developed earlier tumor progression. Binary logistic regression analysis showed that distant metastasis, a high-risk histological subtype, and a maximum tumor diameter of ≥12.5 mm were independent risk factors for RAIR-DTC, and the specificity and sensitivity of a combination of these three parameters for the prediction of RAIR-DTC were 98.0 % and 56.8 %, respectively. Decision curve analysis and the calibration curve revealed that the combined prediction of these three parameters had good repeatability and accuracy. CONCLUSION: The clinicopathological features of DTC can effectively predict the effects of iodine therapy. A combination of distant metastasis, a high-risk histological subtype, and a maximum tumor diameter of ≥12.5 mm showed significantly higher prediction accuracy.
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Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/patologia , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Adenocarcinoma/tratamento farmacológico , PrognósticoRESUMO
The chrysanthemum DgLsL gene, homologous with tomato Ls, is one of the earliest expressed genes controlling axillary meristem initiation. In this study, the wild-type chrysanthemum (CW) and DgLsL-overexpressed line 15 (C15) were used to investigate the regulatory mechanism of axillary bud development in chrysanthemum. Transcriptome sequencing was carried out to detect the differentially expressed genes of the axillary buds 0 h, 24 h and 48 h after decapitation. The phenotypic results showed that the number of axillary buds of C15 was significantly higher than CW. A total of 9,224 DEGs were identified in C15-0 vs. CW-0, 10,622 DEGs in C15-24 vs. CW-24, and 8,929 DEGs in C15-48 vs. CW-48.GO and KEGG pathway enrichment analyses showed that the genes of the flavonoid, phenylpropanoids and plant hormone pathways appeared to be differentially expressed, indicating their important roles in axillary bud germination. DgLsL reduces GA content in axillary buds by promoting GA2ox expression.These results confirmed previous studies on axillary bud germination and growth, and revealed the important roles of genes involved in plant hormone biosynthesis and signal transduction, aiding in the study of the gene patterns involved in axillary bud germination and growth.
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Chrysanthemum , Reguladores de Crescimento de Plantas , Reguladores de Crescimento de Plantas/genética , Chrysanthemum/genética , Perfilação da Expressão Gênica/métodos , Divisão CelularRESUMO
Due to the complicated histopathological characteristics of clear-cell renal-cell carcinoma (ccRCC), non-invasive prognosis before operative treatment is crucial in selecting the appropriate treatment. A total of 126 345 computerized tomography (CT) images from four independent patient cohorts were included for analysis in this study. We propose a V Bottleneck multi-resolution and focus-organ network (VB-MrFo-Net) using a cascade framework for deep learning analysis. The VB-MrFo-Net achieved better performance than VB-Net in tumor segmentation, with a Dice score of 0.87. The nuclear-grade prediction model performed best in the logistic regression classifier, with area under curve values from 0.782 to 0.746. Survival analysis revealed that our prediction model could significantly distinguish patients with high survival risk, with a hazard ratio (HR) of 2.49 [95% confidence interval (CI): 1.13-5.45, P = 0.023] in the General cohort. Excellent performance had also been verified in the Cancer Genome Atlas cohort, the Clinical Proteomic Tumor Analysis Consortium cohort, and the Kidney Tumor Segmentation Challenge cohort, with HRs of 2.77 (95%CI: 1.58-4.84, P = 0.0019), 3.83 (95%CI: 1.22-11.96, P = 0.029), and 2.80 (95%CI: 1.05-7.47, P = 0.025), respectively. In conclusion, we propose a novel VB-MrFo-Net for the renal tumor segmentation and automatic diagnosis of ccRCC. The risk stratification model could accurately distinguish patients with high tumor grade and high survival risk based on non-invasive CT images before surgical treatments, which could provide practical advice for deciding treatment options.
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OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
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Antineoplásicos , Receptores do Fator de Necrose Tumoral , Camundongos , Animais , Receptores do Fator de Necrose Tumoral/fisiologia , Receptores OX40 , Glicoproteínas de Membrana , Ligantes , Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologiaRESUMO
Primula forbesii Franch. is a unique biennial herb with a strong floral fragrance, making it an excellent material for studying the aroma characteristics of the genus Primula. The floral scent is an important ornamental trait that facilitates fertilization. However, the molecular mechanism regulating the floral scent in Primula is unknown. In order to better understand the biological mechanisms of floral scents in this species, this study used RNA sequencing analysis to discuss the first transcriptome sequence of four flowering stages of P. forbesii, which generated 12 P. forbesii cDNA libraries with 79.64 Gb of clean data that formed 51,849 unigenes. Moreover, 53.26% of the unigenes were annotated using public databases. P. forbesii contained 44 candidate genes covering all known enzymatic steps for the biosynthesis of volatile terpenes, the major contributor to the flower's scent. Finally, 1-deoxy-d-xylulose 5-phosphate synthase gene of P. forbesii (PfDXS2, MK370094), the first key enzyme gene in the 2-c-methyl-d-erythritol 4-phosphate (MEP) pathway of terpenoids, was cloned and functionally verified using virus-induced gene silencing (VIGs). The results showed that PfDXS2-silencing significantly reduced the relative concentrations of main volatile terpenes. This report is the first to present molecular data related to aroma metabolites biosynthesis pathways and the functional characterization of any P. forbesii gene. The data on RNA sequencing provide comprehensive information for further analysis of other plants of the genus Primula.
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Odorantes , Primula , Primula/genética , Perfilação da Expressão Gênica , Transcriptoma , FeromôniosRESUMO
The mechanical properties of crystalline materials are influenced by their deformation behavior, which is associated with their microstructural characteristics. Specifically, crystallographic orientation greatly affects the microscale plastic deformation of individual grains. In this study, experiments and finite element simulations of Berkovich nanoindentations are conducted to investigate the impact of crystallographic orientation in polycrystalline copper. A crystal plasticity constitutive model is developed for copper materials, which accurately captures their indentation mechanical response. The results showed that the indentation behavior of polycrystalline copper exhibits a high degree of anisotropy due to significant variation in slip systems for different crystallographic orientations. This results in different mechanical responses of individual grains and distinct material pileup morphologies on the indented surface. Additionally, the study revealed that crystallographic orientation plays a critical role in determining the indentation size effect. These findings have important implications for the design of materials where plasticity is a crucial factor.
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This study aimed to investigate the interaction between 24-Epibrassinolide (EBR) and melatonin (MT) and their effects on cadmium (Cd)-stressed Primula forbesii Franch. P. forbesii seedlings were hydroponically acclimatized at 6-7 weeks, then treated with Cd (200 µmol L-1), 24-EBR (0.1 µmol L-1), and MT (100 µmol L-1) after two weeks. Cd stress significantly reduced crown width, shoot, root length, shoot fresh weight, and fresh and dry root weights. Herein, 24-EBR, MT, and 24-EBR+MT treatments attenuated the growth inhibition caused by Cd stress and improved the morphology, growth indexes, and ornamental characteristics of P. forbesii under Cd stress. 24-EBR had the best effect by effectively alleviating Cd stress and promoting plant growth and development. 24-EBR significantly increased all growth parameters compared to Cd treatment. In addition, 24-EBR significantly improved the gas exchange parameters, activities of antioxidant enzymes, and the cycle efficiency of AsA-GSH. Furthermore, 24-EBR increased the activities of ascorbate peroxidase (APX), glutathione reductase (GR), dehydroascorbate reductase (DHAR), and monodehydroascorbate reductase (MDHAR) by 127.29%, 61.31%, 61.22%, and 51.04%, respectively, compared with the Cd treatment. Therefore, 24-EBR removed the reactive oxygen species produced by stress, thus protecting plants against stress damage. These results indicate that 24-EBR can effectively enhance the tolerance of P. forbesii to Cd stress.
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Cadmium (Cd) pollution is a global problem affecting soil ecology and plant growth. Abscisic acid (ABA) acts as a growth and stress hormone, regulates cell wall synthesis, and plays an important role in plant responses to stress. There are few studies on the mechanisms behind abscisic acid alleviation of cadmium stress in Cosmos bipinnatus, especially in regards to regulation of the root cell wall. This study examined the effects of different concentrations of abscisic acid at different concentrations of cadmium stress. Through adding 5 µmol/L and 30 µmol/L cadmium, followed by spraying 10 µmol/L and 40 µmol/L ABA in a hydroponic experiment, it was found that under two concentrations of cadmium stress, low concentration of ABA improved root cell wall polysaccharide, Cd, and uronic acid content. Especially in pectin, after the application of low concentration ABA, the cadmium concentration was significantly increased by 1.5 times and 1.2 times compared with the Cd concentration under Cd5 and Cd30 treatment alone, respectively. Fourier-Transform Infrared spectroscopy (FTIR) demonstrated that cell wall functional groups such as -OH and -COOH were increased with exposure to ABA. Additionally, the exogenous ABA also increased expression of three kinds of antioxidant enzymes and plant antioxidants. The results of this study suggest that ABA could reduce Cd stress by increasing Cd accumulation, promoting Cd adsorption on the root cell wall, and activating protective mechanisms. This result could help promote application of C. bipinnatus for phytostabilization of cadmium-contaminated soil.
Assuntos
Asteraceae , Cádmio , Cádmio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Adsorção , Asteraceae/metabolismo , Parede Celular/metabolismo , Raízes de Plantas/metabolismoRESUMO
Lysine malonylation (Kmal) is a recently discovered posttranslational modification, and its role in the response to abiotic stress has not been reported in plants. In this study, we isolated a nonspecific lipid transfer protein, DgnsLTP1, from chrysanthemum (Dendranthema grandiflorum var. Jinba). Overexpression and CRISPR-Cas9-mediated gene editing of DgnsLTP1 demonstrated that the protein endows chrysanthemum with cold tolerance. Yeast 2-hybrid, bimolecular fluorescence complementation, luciferase complementation imaging, and coimmunoprecipitation experimental results showed that DgnsLTP1 interacts with a plasma membrane intrinsic protein (PIP) DgPIP. Overexpressing DgPIP boosted the expression of DgGPX (glutathione peroxidase), increased the activity of GPX, and decreased the accumulation of reactive oxygen species (ROS), thereby enhancing the low-temperature stress tolerance of chrysanthemum, while the CRISPR-Cas9-mediated mutant dgpip inhibited this process. Transgenic analyses in chrysanthemum showed that DgnsLTP1 improves the cold resistance of chrysanthemum in a DgPIP-dependent manner. Moreover, Kmal of DgnsLTP1 at the K81 site prevented the degradation of DgPIP in Nicotiana benthamiana and chrysanthemum, further promoted DgGPX expression, enhanced GPX activity, and scavenged excess ROS produced by cold stress, thereby further enhancing the cold resistance of chrysanthemum.