RESUMEN
BACKGROUND: Following China's official designation as malaria-free country by WHO, the imported malaria has emerged as a significant determinant impacting the malaria reestablishment within China. The objective of this study is to explore the application prospects of machine learning algorithms in imported malaria risk assessment of China. METHODS: The data of imported malaria cases in China from 2011 to 2019 was provided by China CDC; historical epidemic data of malaria endemic country was obtained from World Malaria Report, and the other data used in this study are open access data. All the data processing and model construction based on R, and map visualization used ArcGIS software. RESULTS: A total of 27,088 malaria cases imported into China from 85 countries between 2011 and 2019. After data preprocessing and classification, clean dataset has 765 rows (85 * 9) and 11 cols. Six machine learning models was constructed based on the training set, and Random Forest model demonstrated the best performance in model evaluation. According to RF, the highest feature importance were the number of malaria deaths and Indigenous malaria cases. The RF model demonstrated high accuracy in forecasting risk for the year 2019, achieving commendable accuracy rate of 95.3%. This result aligns well with the observed outcomes, indicating the model's reliability in predicting risk levels. CONCLUSIONS: Machine learning algorithms have reliable application prospects in risk assessment of imported malaria in China. This study provides a new methodological reference for the risk assessment and control strategies adjusting of imported malaria in China.
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Malaria , Humanos , Reproducibilidad de los Resultados , Malaria/epidemiología , Medición de Riesgo , China/epidemiología , Aprendizaje AutomáticoRESUMEN
Macrophages in hypoxic regions of advanced colorectal tumors often exhibit M2-type features, but prefer oxygen-consuming lipid catabolism, which is contradictory in oxygen demand and supply. In this study, the results from bioinformatics analysis and intestinal lesions immunohistochemistry of 40 colorectal cancer patients illustrated that glucose-regulatory protein 78 (GRP78) was positively correlated with M2 macrophages. Furthermore, tumor-secreted GRP78 could enter macrophages and polarize them to M2-type. Mechanistically, entered GRP78 located in lipid droplets of macrophages, and elevated protein stabilization of adipose triglyceride lipase ATGL by interacting with it to inhibit its ubiquitination. Increased ATGL promoted the hydrolysis of triglycerides and the production of arachidonic acid (ARA) and docosahexaenoic acid (DHA). Excessive ARA and DHA interacted with PPARγ to encourage its activation, which mediated the M2 polarization of macrophages. In summary, our study showed that secreted GRP78 in the tumor hypoxic microenvironment mediated the domestication of tumor cells to macrophages and maintained tumor immunosuppressive microenvironment by promoting lipolysis, and the lipid catabolism not only provides energy for macrophages but also plays an important role in maintenance of immunosuppressive properties.
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Neoplasias Colorrectales , Chaperón BiP del Retículo Endoplásmico , Lipólisis , Macrófagos , Humanos , Neoplasias Colorrectales/patología , Glucosa/metabolismo , Lípidos , Macrófagos/metabolismo , Proteínas de Neoplasias/metabolismo , Microambiente TumoralRESUMEN
Colorectal cancer has high morbidity and mortality worldwide, especially in western countries; the incidence of colorectal cancer has been high, which is closely related to the high intake of red meat; and the N-glycolylneuraminic acid (Neu5Gc) is responsible for red meat-induced colorectal cancer. A large number of previous studies have suggested that exogenous Neu5Gc-activated inflammation induced the occurrence of colorectal cancer. However, it has not been known whether the Neu5Gc has a direct inducing effect on colorectal cancer. In this study, we found that Neu5Gc promoted the proliferation of colorectal cancer cells and normal intestinal epithelial cells, and further screened out 98 Neu5Gc targets related to the occurrence and development of colorectal cancer by network pharmacology. Subsequently, GO and KEGG enrichment analyses of these targets revealed that mainly enriched in the PI3K-Akt signaling pathway. Then, we selected SRC, HRAS, CDK2, CCNA2, and AKT2 as core targets based on the phenomena of the previous experiments and the available literature reports, and then we used AutoDock for molecular docking with Neu5Gc; the results found that these five genes could bind to Neu5Gc stably. In vitro experiments showed that the mRNA levels of SRC, HRAS, AKT2, CDK2, and CCNA2 were upregulated and the protein levels of HRAS, AKT2, and CCNA2 were enhanced in FHC and SW620 cells after Neu5Gc (100 ng/mL) treatment. In conclusion, this study revealed that Neu5Gc probably acted as a carcinogen that stimulates the expression of proto-oncogene HRAS and the PI3K-Akt pathway and accelerated cell cycle progression. These findings revealed a novel mechanism that Neu5Gc promoted the occurrence and development of colorectal cancer.
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Neoplasias Colorrectales , Farmacología en Red , Humanos , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt , Neoplasias Colorrectales/genéticaRESUMEN
JmjC-domain-containing (JmjC) protein, an important kind of histone demethylase in plants, plays key roles in multiple growth and development processes and in adversity resistance. In this study, we found that OsJMJ703, a known histone demethylase, is expressed in various tissues. Furthermore, over-expression of OsJMJ703 influenced the type of rice panicle, and knock-down of the expression of OsJMJ703 showed an earlier flowering time in rice. In addition, OsJMJ703 is involved in abiotic stress. Transgenic rice of over-expressing OsJMJ703 is sensitive to drought stress, whereas knocking down OsJMJ703 enhances the tolerance to drought stress. This study provides a theoretical basis of the biological function of JmjC protein and further promotes the study of drought resistance.
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Sequías , Genes de Plantas , Histona Demetilasas/genética , Oryza/enzimología , Oryza/crecimiento & desarrollo , Desarrollo de la Planta/genética , Estrés Fisiológico/genética , Flores/fisiología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Histona Demetilasas/metabolismo , Especificidad de Órganos/genética , Oryza/efectos de los fármacos , Oryza/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polietilenglicoles/toxicidad , Estrés Fisiológico/efectos de los fármacosRESUMEN
Deciphering the mechanisms underlying plant responses to abiotic stress is key for improving plant stress resistance. Much is known about the regulation of gene expression in response to salt stress at the transcriptional level; however, little is known about this process at the posttranscriptional level. Recently, we demonstrated that SKIP is a component of spliceosome that interacts with clock gene pre-mRNAs and is essential for regulating their alternative splicing and mRNA maturation. In this study, we found that skip-1 plants are hypersensitive to both salt and osmotic stresses, and that SKIP is required for the alternative splicing and mRNA maturation of several salt-tolerance genes, including NHX1, CBL1, P5CS1, RCI2A, and PAT10. A genome-wide analysis revealed that SKIP mediates the alternative splicing of many genes under salt-stress conditions, and that most of the alternative splicing events in skip-1 involve intron retention and can generate a premature termination codon in the transcribed mRNA. SKIP also controls alternative splicing by modulating the recognition or cleavage of 5' and 3' splice donor and acceptor sites under salt-stress conditions. Therefore, this study addresses the fundamental question of how the mRNA splicing machinery in plants contributes to salt-stress responses at the posttranscriptional level, and provides a link between alternative splicing and salt tolerance.
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Empalme Alternativo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/fisiología , Presión Osmótica/efectos de los fármacos , Cloruro de Sodio/farmacología , Estrés Fisiológico/efectos de los fármacos , Factores de Transcripción/metabolismo , Empalme Alternativo/efectos de los fármacos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Secuencia de Bases , Genoma de Planta/genética , Mutación , ARN Mensajero/genética , Estrés Fisiológico/genética , Factores de Transcripción/genéticaRESUMEN
The phytohormone auxin plays a critical role in plant growth and development, and its spatial distribution largely depends on the polar localization of the PIN-FORMED (PIN) auxin efflux carrier family members. In this study, we identify a putative auxin efflux carrier gene in rice, OsPIN3t, which acts in auxin polar transport but is also involved in the drought stress response in rice. We show that OsPIN3t-GFP fusion proteins are localized in plasma membranes, and this subcellular localization changes under 1-N-naphthylphthalamic acid (NPA) treatment. The tissue-specific expression patterns of OsPIN3t were also investigated using a ß-glucuronidase (GUS) reporter, which showed that OsPIN3t was mainly expressed in vascular tissue. The GUS activity in OsPIN3tpro::GUS plants increased by NAA treatment and decreased by NPA treatment. Moreover, knockdown of OsPIN3t caused crown root abnormalities in the seedling stage that could be phenocopied by treatment of wild-type plants with NPA, which indicated that OsPIN3t is involved in the control of polar auxin transport. Overexpression of OsPIN3t led to improved drought tolerance, and GUS activity significantly increased when OsPIN3tpro::GUS plants were subjected to 20% polyethylene glycol stress. Taken together, these results suggest that OsPIN3t is involved in auxin transport and the drought stress response, which suggests that a polar auxin transport pathway is involved in the regulation of the response to water stress in plants.