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BACKGROUND: Amyloidosis is a rare disorder that can be classified into various types, and the most common type is the systemic light chain type. The prognosis of this disease is extremely poor. In general, amyloidosis mainly affects the kidneys and heart and manifests as abnormal proliferation of clonal plasma cells. Cases in which the liver is the primary organ affected by amyloidosis, as in this report, are less common in clinical practice. CASE SUMMARY: A 62-year-old man was admitted with persistent liver dysfunction of unknown cause and poor treatment outcomes. His condition persisted, and he developed chronic liver failure, with severe cholestasis in the later stage that was gradually accompanied by renal injury. Ultimately, he was diagnosed with hepatic amyloidosis through liver biopsy and pathological examination. CONCLUSION: Hepatic amyloidosis rarely occurs in the clinic, and liver biopsy and pathological examination can assist in the accurate and effective diagnosis of this condition.
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Sclerotinia sclerotiorum (Ss) is one of the most devastating fungal pathogens, causing huge yield loss in multiple economically important crops including oilseed rape. Plant resistance to Ss pertains to quantitative disease resistance (QDR) controlled by multiple minor genes. Genome-wide identification of genes involved in QDR to Ss is yet to be conducted. In this study, we integrated several assays including genome-wide association study (GWAS), multi-omics co-localization, and machine learning prediction to identify, on a genome-wide scale, genes involved in the oilseed rape QDR to Ss. Employing GWAS and multi-omics co-localization, we identified seven resistance-associated loci (RALs) associated with oilseed rape resistance to Ss. Furthermore, we developed a machine learning algorithm and named it Integrative Multi-Omics Analysis and Machine Learning for Target Gene Prediction (iMAP), which integrates multi-omics data to rapidly predict disease resistance-related genes within a broad chromosomal region. Through iMAP based on the identified RALs, we revealed multiple calcium signaling genes related to the QDR to Ss. Population-level analysis of selective sweeps and haplotypes of variants confirmed the positive selection of the predicted calcium signaling genes during evolution. Overall, this study has developed an algorithm that integrates multi-omics data and machine learning methods, providing a powerful tool for predicting target genes associated with specific traits. Furthermore, it makes a basis for further understanding the role and mechanisms of calcium signaling genes in the QDR to Ss.
Asunto(s)
Ascomicetos , Brassica napus , Señalización del Calcio , Resistencia a la Enfermedad , Estudio de Asociación del Genoma Completo , Aprendizaje Automático , Enfermedades de las Plantas , Ascomicetos/patogenicidad , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Brassica napus/genética , Brassica napus/microbiología , Brassica napus/inmunología , Señalización del Calcio/genética , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Genómica/métodos , MultiómicaRESUMEN
BACKGROUND: The increased expression of G3BP1 was positively correlated with the prognosis of liver failure. AIM: To investigate the effect of G3BP1 on the prognosis of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) after the treatment of artificial liver support system (ALSS). METHODS: A total of 244 patients with ALF and ACLF were enrolled in this study. The levels of G3BP1 on admission and at discharge were detected. The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis. RESULTS: This study was shown that lactate dehydrogenase (LDH), alpha-fetoprotein (AFP) and prothrombin time were closely related to the prognosis of patients. After the ALSS treatment, the patient' amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission (difG3BP1) < 0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index. The subgroup analysis showed that the difG3BP1 < 0 group had a higher risk of progression, regardless of model for end-stage liver disease high-risk or low-risk group. At the same time, compared with the inflammatory marks [tumor necrosis factor-α, interleukin (IL)-1ß and IL-18], G3BP1 had higher discrimination and was more stable in the model analysis and validation set. When combined with AFP and LDH, concordance index was respectively 0.84 and 0.8 in training and validation cohorts. CONCLUSION: This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS. The combination of G3BP1, AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.
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Extracellular deposition of ß-amyloid (Aß) and intracellular hyperphosphorylated tau are the predominant pathological changes in Alzheimer's disease (AD). Increasing evidence demonstrates a critical role of a variety of small GTPases, namely Ras-related proteins (Rabs), in the pathogenesis of AD. As crucial regulators of intracellular membrane trafficking, alteration in Rab protein expression and function represents one of the primary factors contributing to the abnormal membrane trafficking in AD. Additionally, the Rab GTPases are also involved in the development of Aß, tau and other pathological changes associated with AD. In this article, we conduct a comprehensive review on the primary functions of multiple Rab proteins and their involvement in the pathogenesis of AD.