A domain-agnostic approach for characterization of lifelong learning systems.

Despite the advancement of machine learning techniques in recent years, state-of-the-art systems lack robustness to "real world" events, where the input distributions and tasks encountered by the deployed systems will not be limited to the original training context, and systems will instead need to adapt to novel distributions and tasks while deployed. This critical gap may be addressed through the development of "Lifelong Learning" systems that are capable of (1) Continuous Learning, (2) Transfer and Adaptation, and (3) Scalability. Unfortunately, efforts to improve these capabilities are typically treated as distinct areas of research that are assessed independently, without regard to the impact of each separate capability on other aspects of the system. We instead propose a holistic approach, using a suite of metrics and an evaluation framework to assess Lifelong Learning in a principled way that is agnostic to specific domains or system techniques. Through five case studies, we show that this suite of metrics can inform the development of varied and complex Lifelong Learning systems. We highlight how the proposed suite of metrics quantifies performance trade-offs present during Lifelong Learning system development - both the widely discussed Stability-Plasticity dilemma and the newly proposed relationship between Sample Efficient and Robust Learning. Further, we make recommendations for the formulation and use of metrics to guide the continuing development of Lifelong Learning systems and assess their progress in the future.

Inhibition of JAK2/STAT3 signaling pathway by panaxadiol limits the progression of pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer-related death with the characteristics of chemoresistance and early metastasis. Panaxadiol, a triterpenoid saponin extracted from the roots of American ginseng, has been proved to display anti-tumor activity in colon cancer. In this study, we found panaxadiol significantly inhibited proliferation, and induced apoptosis in human pancreatic cancer cell lines PANC-1 and Patu8988 in a dose-dependent manner. Furthermore, the expression of apoptosis-related proteins (Bax, Bcl2, Cleaved-caspase3) was detected via western blot and immunofluorescence staining. In addition, panaxadiol was also found to inhibit the migration of pancreatic cancer cells by wound healing and transwell assays. In vivo, the growth of xenograft pancreatic cancer models was also notably suppressed by panaxadiol compared to the control group. Moreover, the down-regulation of JAK2-STAT3 signaling pathway was responsible for the underlying pro-apoptosis mechanism of panaxadiol, and this result was in good agreement with molecular docking analysis between panaxadiol and STAT3. In conclusion, our work comprehensively explored the anti-tumor ability in PANC-1 and Patu8988 cells of panaxadiol and provided a potential choice for the clinical treatment of pancreatic cancer patients.

Study of the Mechanism by Which Curcumin Cooperates with Sestrin2 to Inhibit the Growth of Pancreatic Cancer.

BACKGROUND: Pancreatic carcinoma is a malignant tumor with a high fatality rate, and the increased resistance of pancreatic carcinoma to chemotherapy has become a difficult problem in clinical practice. Hence, it is imperative to develop an effective treatment for pancreatic cancer. Sestrins are a class of stress-induced proteins that have antioxidation functions, regulating cell growth and metabolism. Curcumin is a natural pigment isolated from turmeric. Several studies have also suggested that this molecule has multiple pharmacological effects, such as anti-inflammatory, antioxidant, and antitumor effects. However, there are insufficient studies on curcumin cooperating with the sestrin family to inhibit tumors, and the mechanism is still unclear. Our aim was to observe the potential anticancer effects of curcumin combined with the sestrin family on pancreatic carcinoma and probe its possible molecular mechanisms. METHODS: Lentiviral infection, real-time fluorescence quantitative PCR assays, Cell Counting Kit-8 assays, real-time cell analysis technology, colony formation assays, wound healing assays, Transwell invasion assays, protein extraction, and western blots (WBs) were used to evaluate the effect of curcumin combined with sestrin2 on the proliferation, invasion, and migration of pancreatic carcinoma cells. RESULTS: The results revealed that curcumin cooperated with sestrin2 to significantly suppress pancreatic cancer. In addition, we determined that sestrin2 cooperated with curcumin to inhibit pancreatic cancer by specifically targeting Nrf2/Keap1/HO-1/NQO-1. CONCLUSION: These findings clarify that curcumin-mediated synergistic targeting of sestrin2 is a potentially valuable treatment for pancreatic cancer.

Discoveries in Pancreatic Physiology and Disease Biology Using Single-Cell RNA Sequencing.

Transcriptome analysis is used to study gene expression in human tissues. It can promote the discovery of new therapeutic targets for related diseases by characterizing the endocrine function of pancreatic physiology and pathology, as well as the gene expression of pancreatic tumors. Compared to whole-tissue RNA sequencing, single-cell RNA sequencing (scRNA-seq) can detect transcriptional activity within a single cell. The scRNA-seq had an invaluable contribution to discovering previously unknown cell subtypes in normal and diseased pancreases, studying the functional role of rare islet cells, and studying various types of cells in diabetes as well as cancer. Here, we review the recent in vitro and in vivo advances in understanding the pancreatic physiology and pathology associated with single-cell sequencing technology, which may provide new insights into treatment strategy optimization for diabetes and pancreatic cancer.

Upregulation of oxidative stress-responsive 1(OXSR1) predicts poor prognosis and promotes hepatocellular carcinoma progression.

Many studies reported that Oxidative stress-responsive 1(OXSR1) is closely related to the malignant progression of several malignancies. Nevertheless, the expression pattern and function of OXSR1 in HCC remains unknown. In present research, it was observed that the expression of OXSR1 was abnormally elevated in HCC. Upregulated OXSR1 was associated with TNM stage, and grade and was confirmed as an independent prognostic factor in HCC patients. The downregulation of OXSR1 expression effectively repressed the proliferation, migration and invasion of HCC in vivo and in vitro experiments. Western blot and qRT-PCR analysis demonstrated that mutant p53-R249S was critical for regulating the aberrant elevation of OXSR1 in HCC. Chip assay indicated that p53-R249S abrogated the binding of p53 to the OXSR1 promoter region and increased the level of POL2, H3Kac and H4Kac in the promoter region of the OXSR1, thus promoting the transcriptional expression of OXSR1. GSEA revealed that numerous cancer-related pathways were enriched in the high OXSR1 expression group. Furthermore, the expression level of OXSR1 was positively correlated with the infiltration levels of tumor infiltrating immune cells (TIICs) and PD-L1 expression in HCC by TIMER platform. In summary, our study revealed that upregulated OXSR1 was a determinant of prognosis and immune infiltration in HCC. The expression of OXSR1 was released by p53-R249S mutant, and upregulated OXSR1 in HCC promoted proliferation, migration and invasion.