RESUMO

Pain catastrophizing is a prominent psychological factor that is strongly correlated with pain. Although the complex properties of pain catastrophizing vary across different pain phases, the contribution of chronic pain to its progression from a general trait to a higher state remains unclear. This study aimed to examine the neural mechanisms and degree to which pain catastrophizing is reinforced in the context of primary dysmenorrhea (PDM), one of the most prevalent gynaecological complaints experienced by women of reproductive age. Altogether, 29 women with moderate-to-severe PDM were included in this study. Arterial spin labelling was used to quantify the cerebral blood flow (CBF) in each participant in both the pain-free and painful phases. The pain catastrophizing scale (PCS) was completed in two phases, and the Short-Form McGill Pain Questionnaire was completed in the painful phase. Compared with pain catastrophizing in the pain-free phase (PCSpf), pain catastrophizing in the painful phase (PCSp) is higher and positively correlated with the composite factor of menstrual pain. CBF analysis indicated that the PCSp is positively associated with CBF in the frontal cortex, hippocampus and amygdala. The reinforcement of pain catastrophizing correlates with CBF in the prefrontal cortex. Specifically, the medial prefrontal cortex, which correlates with pain state, plays a crucial role in mediating the reinforcing effect of pain in the PCSp. These results promote the mechanical comprehension of pain catastrophizing management in individuals with chronic pain.

RESUMO

OBJECTIVE: The aim of this study was to explore the clinical application value of two-dimensional ultrasound (2D-US) combined with contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign, borderline ovarian tumors (BOTs), and malignant ovarian epithelial tumors (OETs). METHODS: The clinical data of 108 patients who underwent surgery for pathologically confirmed of OETs at Peking University People's Hospital between December 2018 and November 2023 were retrospectively studied. The diagnostic value of 2D-US combined with CEUS for diagnosing OETs was analyzed using chi-square tests, receiver operating characteristic (ROC) curves, and random forest models. RESULTS: Among the 108 cases of OETs, 23 were benign, 34 were BOTs, and 51 were malignant. Chi-square tests confirmed that the perfusion pattern of the contrast agent plays an important role in the differential diagnosis of OETs. Compared with those in the benign group, the BOTs were not significantly different in terms of perfusion phase and enhancement intensity, but the regression time of the BOTs was earlier (P < 0.05). Compared with the BOTs, the malignant tumors group showed earlier perfusion and higher enhancement intensity, with no significant difference in regression time. The ROC curve results indicated that the combined diagnostic efficiency of 2D-US and CEUS in distinguishing OETs was significantly higher than that of a single diagnostic technique in terms of sensitivity, specificity, accuracy, and AUC. The random forest model results revealed that among the various parameters used in the differential diagnosis of OETs, the perfusion pattern was the most significant factor. CONCLUSION: 2D-US combined with CEUS helps improve the differential diagnostic efficiency for benign, BOTs, and malignant OETs.

Assuntos

RESUMO

Integrins play critical roles in connecting the extracellular matrix and actin. While the upregulation of integrins is thought to promote cancer stemness and metastasis, the mechanisms underlying their upregulation in cancer stem cells (CSCs) remain poorly understood. Herein, we show that USP22 is essential in maintaining breast cancer cell stemness by promoting the transcription of integrin ß1 (ITGB1). Both genetic and pharmacological inhibition of USP22 largely impaired breast CSCs self-renewal and prevented their metastasis. Reconstitution of integrin ß1 partially rescued USP22-null breast cancer metastasis. USP22 functions as a bona fide deubiquitinase to protect the proteasomal degradation of the forkhead box M1 (FoxM1), a transcription factor for tumoral ITGB1 gene transcription. Immunohistochemistry staining detected a positive correlation among USP22, FoxM1, and integrin ß1 in human breast cancers. Collectively, our study identifies the USP22-FoxM1-integrin ß1 signaling axis as critical for cancer stemness and offers a potential target for antitumor therapy.

RESUMO

The fall armyworm (FAW), Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), poses a significant threat to food security, necessitating effective management strategies. While chemical control remains a primary approach, understanding the toxicity and detoxification mechanisms of different insecticides is crucial. In this study, we conducted leaf-dipping bioassays to assess the toxicity of quinalphos and beta-cypermethrin·emamectin benzoate (ß-cyp·EMB) on S. frugiperda larvae. Additionally, we assessed the response of alterations in CarE, GST, MFO, and AChE activities to sublethal concentrations of these insecticides over various treatment durations. Results indicated that ß-cyp·EMB exhibited higher toxicity than quinalphos in S. frugiperda. Interestingly, the highest activities of GST, CarE, MFO, and AChE were observed at 6 h exposure to LC10 and LC25 of ß-cyp·EMB, surpassing equivalent sublethal concentrations of quinalphos. Subsequently, GST and CarE activities exposure to ß-cyp·EMB steadily decreased, while MFO and AChE activities exposure to both insecticides was initially decreased then increased. Conversely, two sublethal concentrations of quinalphos notably enhanced GST activity across all exposure durations, with significantly higher than ß-cyp·EMB at 12-48 h. Similarly, CarE activity was also increased at various durations. Our research has exhibited significant alterations in enzyme activities exposure to both concentration and duration. Furthermore, Pearson correlation analysis showed significant correlations among these enzyme activities at different treatment durations. These findings contribute to a better understanding of detoxification mechanisms across different insecticides, providing valuable insights for the rational management of S. frugiperda populations.

Assuntos

RESUMO

The atrazine (ATR) is extensively used in dryland crops like corn and sorghum in black soil region of Northeast China, posing ecological risks due to toxic metabolites. Vermicompost are known for soil organic pollution remediation but their role in pesticide degradation in black soil remains understudied. The influence of vermicompost on the microbial degradation pathway of atrazine was assessed in this study. Although vermicompost didn't significantly boost atrazine removal, they notably aided in primary metabolite degradation, hydroxyatrazine (HYA), deisopropylatrazine (DIA), and deethylatrazine (DEA), reducing their content by 38.67 %. They also altered the soil microbial community structure, favoring atrazine-degrading bacteria like Proteobacteria, Firmicutes, and Actinobacteria. Five secondary degradation products were identified in vermicompost treatments. Atrazine degradation occurred via dechlorination, dealkylation, and deamination pathways mainly by Nocardioidacea, Streptomycetaceae, Bacillaceae, Sphingomonadaceae, Comamonadaceae and Nitrososphaeraceae. pH and available nitrogen (AN) influenced microbial community structure and atrazine degradation, correlating with vermicompost application rates. Future black soil remediation should optimize application rates based on atrazine content and soil properties.

Assuntos

RESUMO

Objective: To explore the effect of Gouqi Nuzhen Liuhe Decoction (GNLHD) on the PI3K/mTOR Signaling Pathway for Premature Ovarian Insufficiency (POI) based on system pharmacology. Methods: First, the system pharmacology approach was used to predict the mechanism of GNLHD. Then, mice were randomly divided into model group, positive group, GNLHD high-dose group, GNLHD medium-dose group, and GNLHD low-dose group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of ovarian tissue under light microscope. The expression levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by enzyme-linked immunosorbent assay. The expressions of PI3K, AKT1 and mTOR proteins in ovarian tissue were detected by immunohistochemistry. Results: The results of system pharmacology showed that GNLHD may regulate biological processes and signaling pathways such as: reproductive structure development, reproductive system development, Oocyte meiosis and so on. Compared with the model group, the levels of E2 in the GNLHD group were increased, and the levels of FSH and LH were decreased (P < 0.05). Compared with the model group, the number of mature follicles in the GNLHD group was significantly increased, the number of atretic follicles was relatively decreased, and the expressions of PI3K, AKT1, and MTOR proteins in the GNLHD group were significantly increased (P < 0.05). Conclusion: GNLHD may improve the ovarian function of POI mice by affecting the expression of PI3K, AKT1 and mTOR proteins, promote the growth and development of follicles, increase the E2 level, reduce FSH and LH level, and maintain the stability of the ovarian internal environment.

RESUMO

The mitochondria­associated endoplasmic reticulum (ER) membrane (MAM), serving as a vital link between the mitochondria and ER, holds a pivotal role in maintaining the physiological function of these two organelles. Its specific functions encompass the participation in the biosynthesis and functional regulation of the mitochondria, calcium ion transport, lipid metabolism, oxidative stress and autophagy among numerous other facets. Scientific exploration has revealed that MAMs hold potential as effective therapeutic targets influencing the mitochondria and ER within the context of cancer therapy. The present review focused on elucidating the related pathways of mitochondrial autophagy and ER stress and their practical application in ovarian cancer, aiming to identify commonalities existing between MAMs and these pathways, thereby extending to related applications of MAMs in ovarian cancer treatment. This endeavor aimed at exploring new potential for MAMs in clinically managing ovarian cancer.

Assuntos

RESUMO

Introduction: The rapid development of artificial intelligence (AI) in healthcare has exposed the unmet need for growing a multidisciplinary workforce that can collaborate effectively in the learning health systems. Maximizing the synergy among multiple teams is critical for Collaborative AI in Healthcare. Methods: We have developed a series of data, tools, and educational resources for cultivating the next generation of multidisciplinary workforce for Collaborative AI in Healthcare. We built bulk-natural language processing pipelines to extract structured information from clinical notes and stored them in common data models. We developed multimodal AI/machine learning (ML) tools and tutorials to enrich the toolbox of the multidisciplinary workforce to analyze multimodal healthcare data. We have created a fertile ground to cross-pollinate clinicians and AI scientists and train the next generation of AI health workforce to collaborate effectively. Results: Our work has democratized access to unstructured health information, AI/ML tools and resources for healthcare, and collaborative education resources. From 2017 to 2022, this has enabled studies in multiple clinical specialties resulting in 68 peer-reviewed publications. In 2022, our cross-discipline efforts converged and institutionalized into the Center for Collaborative AI in Healthcare. Conclusions: Our Collaborative AI in Healthcare initiatives has created valuable educational and practical resources. They have enabled more clinicians, scientists, and hospital administrators to successfully apply AI methods in their daily research and practice, develop closer collaborations, and advanced the institution-level learning health system.

RESUMO

The human brain is a dynamic system that shows frequency-specific features. Neuroimaging studies have shown that both healthy individuals and those with chronic pain disorders experience pain influenced by various processes that fluctuate over time. Primary dysmenorrhea (PDM) is a chronic visceral pain that disrupts the coordinated activity of brain's functional network. However, it remains unclear whether the dynamic interactions across the whole-brain network over time and their associations with neurobehavioral symptoms are dependent on the frequency bands in patients with PDM during the pain-free periovulation phase. In this study, we used an energy landscape analysis to examine the interactions over time across the large-scale network in a sample of 59 patients with PDM and 57 healthy controls (HCs) at different frequency bands. Compared with HCs, patients with PDM exhibit aberrant brain dynamics, with more significant differences in the slow-4 frequency band. Patients with PDM show more indirect neural transition counts due to an unstable intermediate state, whereas neurotypical brain activity frequently transitions between 2 major states. This data-driven approach further revealed that the brains of individuals with PDM have more abnormal brain dynamics than HCs. Our results suggested that unstable brain dynamics were associated with the strength of brain functional segregation and the Pain Catastrophizing Scale score. Our findings provide preliminary evidence that atypical dynamics in the functional network may serve as a potential key feature and biological marker of patients with PDM during the pain-free phase. PERSPECTIVE: We applied energy landscape analysis on brain-imaging data to identify relatively stable and dominant brain activity patterns for patients with PDM. More atypical brain dynamics were found in the slow-4 band and were related to the strength of functional segregation, providing new insights into the dysfunction brain dynamics.

Assuntos

RESUMO

To date, there has been no high-quality sequence for genomes of the East Asian grape species, hindering biological and breeding efforts to improve grape cultivars. This study presents ~522 Mb of the Vitis amurensis (Va) genome sequence containing 27 635 coding genes. Phylogenetic analysis indicated that Vitis riparia (Vr) may have first split from the other two species, Va and Vitis vinifera (Vv). Divergent numbers of duplicated genes reserved among grapes suggests that the core eudicot-common hexaploidy (ECH) and the subsequent genome instability still play a non-negligible role in species divergence and biological innovation. Prominent accumulation of sequence variants might have improved cold resistance in Va, resulting in a more robust network of regulatory cold resistance genes, explaining why it is extremely cold-tolerant compared with Vv and Vr. In contrast, Va has preserved many fewer nucleotide binding site (NBS) disease resistance genes than the other grapes. Notably, multi-omics analysis identified one trans-cinnamate 4-monooxygenase gene positively correlated to the resveratrol accumulated during Va berry development. A selective sweep analysis revealed a hypothetical Va sex-determination region (SDR). Besides, a PPR-containing protein-coding gene in the hypothetical SDR may be related to sex determination in Va. The content and arrangement order of genes in the putative SDR of female Va were similar to those of female Vv. However, the putative SDR of female Va has lost one flavin-containing monooxygenase (FMO) gene and contains one extra protein-coding gene uncharacterized so far. These findings will improve the understanding of Vitis biology and contribute to the improvement of grape breeding.

RESUMO

High malignancy is a prominent characteristic of epithelial ovarian cancer (EOC), emphasizing the necessity for further elucidation of the potential mechanisms underlying cancer progression. Aneuploidy and copy number variation (CNV) partially contribute to the heightened malignancy observed in EOC; however, the precise features of aneuploidy and their underlying molecular patterns, as well as the relationship between CNV and aneuploidy in EOC, remain unclear. In this study, we employed single-cell sequencing data along with The Cancer Genome Atlas (TCGA) to investigate aneuploidy and CNV in EOC. The technique of fluorescence in situ hybridization (FISH) was employed using specific probes. The copy number variation within the genomic region of chromosome 8 (42754568-47889815) was assessed and utilized as a representative measure for the ploidy status of individual cells in chromosome 8. Differential expression analysis was performed between different subgroups based on chromosome 8 ploidy. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and hub-gene analyses were subsequently utilized to identify crucial genes involved. By classifying enriched tumor cells into distinct subtypes based on chromosome 8 ploidy combined with TCGA data integration, we identified key genes driving chromosome 8 aneuploidy in EOC, revealing that PRKDC gene involvement through the mediated non-homologous end-joining pathway may play a pivotal role in disease progression. Further validation through analysis of the GEO and TCGA database and survival assessment, considering both mRNA expression levels and CNV status of PRKDC, has confirmed its involvement in the progression of EOC. Further functional analysis revealed an upregulation of PRKDC in both ovarian EOC cells and tissues, with its expression showing a significant correlation with the extent of copy number variation (CNV) on chromosome 8. Taken together, CNV amplification and aneuploidy of chromosome 8 are important characteristics of EOC. PRKDC and the mediated NHEJ pathway may play a crucial role in driving aneuploidy on chromosome 8 during the progression of EOC.

Assuntos

RESUMO

Biofilms are thought to play a vital role in the beneficial effects of probiotic bacteria. However, the structure and function of probiotic biofilms are poorly understood. In this work, biofilms of Escherichia coli (E. coli) Nissle 1917 were investigated and compared with those of pathogenic and opportunistic strains (E. coli MG1655, O157:H7) using crystal violet assay, confocal laser scanning microscopy, scanning electron microscopy and FTIR microspectroscopy. The study revealed significant differences in the morphological structure, chemical composition, and spatial heterogeneity of the biofilm formed by the probiotic E. coli strain. In particular, the probiotic biofilm can secrete unique phospholipid components into the extracellular matrix. These findings provide new information on the morphology, architecture and chemical heterogeneity of probiotic biofilms. This information may help us to understand the beneficial effects of probiotics for various applications.

RESUMO

Therapeutic antibodies have become one of the most influential therapeutics in modern medicine to fight against infectious pathogens, cancer, and many other diseases. However, experimental screening for highly efficacious targeting antibodies is labor-intensive and of high cost, which is exacerbated by evolving antigen targets under selective pressure such as fast-mutating viral variants. As a proof-of-concept, we developed a machine learning-assisted antibody generation pipeline AbGen that greatly accelerates the screening and re-design of immunoglobulins G (IgGs) against a broad spectrum of SARS-CoV-2 coronavirus variant strains. Our AbGen centers around a novel antibody language model (AbLM) that is pretrained on 12 million generic protein domain sequences and fine-tuned on 4,000+ paired VH-VL sequences, with IgG-specific CDR-masking and VH-VL cross-attention. AbLM provides a latent space of IgG sequence embeddings for AbGen, including (a) landscapes of IgGs' activities in neutralizing the wild-type virus are analyzed through structure prediction for IgG and IgG-antigen (viral protein spike's receptor binding domain, RBD) interactions; and (b) landscapes of IgGs' susceptibility in neutralizing variant viruses are predicted through Gaussian process regression, despite that as few as 14 clinical antibodies' responses to variants of concern are available. The AbGen pipeline was applied to over 1300 IgG sequences we collected from RBD-binding B cells of convalescent patients. With experimental validations, AbGen efficiently prioritized IgG candidates against a broad spectrum of viral variants (wildtype, Delta, and Omicron), preventing the infection of host cells in vitro and hACE2 transgenic mice in vivo . Compared to other existing protein language models that require 10-100 times more model parameters, AbLM improved the precision from around 50% to 75% to predict IgGs with low variant susceptibility. Furthermore, AbGen enables structure-based computational protein redesign for selected IgG clones with single amino acid substitutions at the RBD-binding interface that doubled the IgG blockade efficacy for one of the severe, therapy-resistant strains - Delta (B.1.617). Our work expedites applications of artificial intelligence in antibody screen and re- design combining data-driven protein language models and Kriging for antibody sequence analysis and activity prediction, in synergy with physics-driven protein docking and design for antibody-antigen interface analyses and functional optimization.

RESUMO

Food-derived peptides have been extensively studied for their benefits in humans. Hen eggs, characterized by high protein and digestibility, are an excellent source of food-derived bioactive peptides. This review summarizes the preparation methods, purification, and identification of hen egg-derived peptides (HEPs). The preparation methods mainly include enzymatic hydrolysis, microbial fermentation, and chemical synthesis. Genetic engineering is an emerging trend of HEP preparation. Then, we summarize the biological activities of HEPs, such as antioxidant activities, enzyme inhibitory activity, and antibacterial activity, of which the enzyme inhibitory activity is comprehensively summarized for the first time. The structure-activity relationship and underlying mechanism of the HEPs are further elucidated. Finally, the applications, future challenges, and opportunities of HEPs were mainly discussed in the food and non-food sectors. We focus on the potential applications of HEPs in intestinal health and assembly delivery and provide a reference for the further utilization and commercial development of HEPs.

RESUMO

Traumatic brain injuries (TBI) and stroke are major causes of morbidity and mortality in both developing and developed countries. The complex and heterogeneous pathophysiology of TBI and cerebral ischemia-reperfusion injury (CIRI), in addition to the blood-brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)-responsive neutrophil-targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.

Assuntos

RESUMO

The fall armyworm, Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), a common agricultural pest known for its extensive migration and wide host ranges, causes considerable harm to maize (Zea mays L.). In this study, we utilized two molecular marker genes, COI and Tpi, to compare the genetic characteristics of the collected original samples. Additionally, through an interactive study between S. frugiperda larvae and six maize varieties aiming to understand the insect's adaptability and resistance mechanisms, our analysis revealed that both the COI and Tpi genes identified S. frugiperda as the corn strain. Further examination of the larvae showed significant differences in nutritional indices, digestive, and detoxification enzyme activities. Special maize varieties were found to offer higher efficiency in nutrient conversion and assimilation compared with common varieties. This study revealed adaptations in S. frugiperda's digestive and detoxification processes in response to the different maize varieties. For instance, larvae reared on common maize exhibited elevated amylase and lipase activities. Interestingly, detoxification enzyme activities exhibited different patterns of variation in different maize varieties. The Pearson correlation analysis between nutritional indices, enzyme activities, and the nutritional content and secondary metabolites of maize leaves provided deeper insights into the pest's adaptability. The results highlighted significant relationships between specific nutritional components in maize and the physiological responses of S. frugiperda. Overall, our findings contribute substantially to the understanding of S. frugiperda's host plant adaptability, offering critical insights for the development of sustainable pest management strategies.

RESUMO

The high level of alpha-fetoprotein (AFP) expression is closely related to hepatocellular carcinoma (HCC). Herein, a dual signal ratiometric electrochemical immunosensor based on chitosan-ferrocenecarboxaldehyde-spindle gold (Chit-Fc-SAu) and Co/Fe metal-organic framework-toluidine blue/polydopamine (Co/Fe MOF-TB/PDA) was proposed for quantitative analysis of AFP. Specifically, Chit-Fc-SAu worked as a substrate to trap more primary antibodies (Ab1) generating the first electrochemical signal from Fc. Thanks to the large specific surface area, the synergistic and electronic effects of Co/Fe MOF nanosheets, and the rich functional groups of PDA, Co/Fe MOF-TB/PDA could load more secondary antibodies (Ab2) and signal molecules (TB) providing another amplified electrochemical signal. In the presence of AFP, Ab1-AFP-Ab2 formed a sandwich structure, and as the AFP concentration increased, the peak current ratio of TB to Fc (ITB/IFc) also increased. The dual signal ratiometric strategy can avoid environmental signal interference and achieve signal self-calibration, thereby improving the accuracy and reproducibility of detection. After a series of exploration, this self-calibrated ratiometric immunosensor exhibited a wide linear range (0.001-200 ng mL-1), a low detection limit (0.34 pg mL-1), and good repeatability. When applied to the assay of clinical serum samples, the detection results of ratiometric sensor were consistent with that of commercial electrochemiluminescence (ECL) immunoassay, significantly superior to that of non-ratiometric sensor. The self-calibrated strategy based on ratiometric sensor helps to improve the accuracy of AFP in clinical diagnosis.

Assuntos

RESUMO

This study generated whole genome DNA methylation maps to characterize DNA methylomes of grape (cv. 'Cabernet Franc') skins and examine their functional significance during grape skin coloration. We sampled grape skin tissues at three key stages (the early stage of grape berry swelling, the late stage of grape berry swelling and the veraison) during which the color of grape berries changed from green to red. DNA methylation levels of grape skins at the three stages were higher in transposable element regions than in the genic regions, and the CG and CHG DNA methylation levels of the genic region were higher than the CHH DNA methylation levels. We identified differentially methylated regions (DMRs) in S2_vs_S1 and S3_vs_S1. The results indicated that DMRs predominantly occurred within the CHH context during grape skin coloration. Many gene ontology (GO)-enriched DMR-related genes were involved in "nucleotide binding," "catalytic activity" and "ribonucleotide binding" terms; however, many KEGG-enriched DMR-related genes were involved in the "flavonoid biosynthesis" pathway. Our results could provide an important foundation for future research on the development mechanism of grape berries.

Assuntos

RESUMO

Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells. IMPLICATIONS: Our studies uncover a novel mechanism that fine-tunes oncogenic KIT signaling in leukemia cells and will likely identify PRL2 as a novel therapeutic target in AML with KIT mutations.

Assuntos