Continual Learning With Unknown Task Boundary.

Most existing studies on continual learning (CL) consider the task-based setting, where task boundaries are known to learners during training. However, they may be impractical for real-world problems, where new tasks arrive with unnotified distribution shifts. In this article, we introduce a new boundary-unknown continual learning scenario called continuum incremental learning (CoIL), where the incremental unit may be a concatenation of several tasks or a subset of one task. To identify task boundaries, we design a continual out-of-distribution (OOD) detection method based on softmax probabilities, which can detect OOD samples for the latest learned task. Then, we incorporate it with continual learning approaches to solve the CoIL problem. Furthermore, we investigate the more challenging task-reappear setting and propose a method named continual learning with unknown task boundary (CLUTaB). CLUTaB first adopts in-distribution detection and OOD loss to determine whether a set of data is sampled from any learned distribution. Then, a two-step inference technique is designed to improve the continual learning performance. Experiments show that our methods work well with existing continual learning approaches and achieve good performance on CIFAR-100 and mini-ImageNet datasets.

Adoptive cell immunotherapy for breast cancer: harnessing the power of immune cells.

Breast cancer is the most prevalent malignant neoplasm worldwide, necessitating the development of novel therapeutic strategies owing to the limitations posed by conventional treatment modalities. Immunotherapy is an innovative approach that has demonstrated significant efficacy in modulating a patient's innate immune system to combat tumor cells. In the era of precision medicine, adoptive immunotherapy for breast cancer has garnered widespread attention as an emerging treatment strategy, primarily encompassing cellular therapies such as tumor-infiltrating lymphocyte therapy, chimeric antigen receptor T/NK/M cell therapy, T-cell receptor gene-engineered T-cell therapy, lymphokine-activated killer cell therapy, cytokine-induced killer cell therapy, natural killer cell therapy, and γδ T cell therapy, among others. This treatment paradigm is based on the principles of immune memory and antigen specificity, involving the collection, processing, and expansion of the patient's immune cells, followed by their reintroduction into the patient's body to activate the immune system and prevent tumor recurrence and metastasis. Currently, multiple clinical trials are assessing the feasibility, effectiveness, and safety of adoptive immunotherapy in breast cancer. However, this therapeutic approach faces challenges associated with tumor heterogeneity, immune evasion, and treatment safety. This review comprehensively summarizes the latest advancements in adoptive immunotherapy for breast cancer and discusses future research directions and prospects, offering valuable guidance and insights into breast cancer immunotherapy.

FN1 mediated activation of aspartate metabolism promotes the progression of triple-negative and luminal a breast cancer.

BACKGROUND: Breast cancer (BC) is regarded as one of the most common cancers diagnosed among the female population and has an extremely high mortality rate. It is known that Fibronectin 1 (FN1) drives the occurrence and development of a variety of cancers through metabolic reprogramming. Aspartic acid is considered to be an important substrate for nucleotide synthesis. However, the regulatory mechanism between FN1 and aspartate metabolism is currently unclear. METHODS: We used RNA sequencing (RNA seq) and liquid chromatography-mass spectrometry to analyze the tumor tissues and paracancerous tissues of patients. MCF7 and MDA-MB-231 cells were used to explore the effects of FN1-regulated aspartic acid metabolism on cell survival, invasion, migration and tumor growth. We used PCR, Western blot, immunocytochemistry and immunofluorescence techniques to study it. RESULTS: We found that FN1 was highly expressed in tumor tissues, especially in Lumina A and TNBC subtypes, and was associated with poor prognosis. In vivo and in vitro experiments showed that silencing FN1 inhibits the activation of the YAP1/Hippo pathway by enhancing YAP1 phosphorylation, down-regulates SLC1A3-mediated aspartate uptake and utilization by tumor cells, inhibits BC cell proliferation, invasion and migration, and promotes apoptosis. In addition, inhibition of FN1 combined with the YAP1 inhibitor or SLC1A3 inhibitor can effectively inhibit tumor growth, of which inhibition of FN1 combined with the YAP1 inhibitor is more effective. CONCLUSION: Targeting the "FN1/YAP1/SLC1A3/Aspartate metabolism" regulatory axis provides a new target for BC diagnosis and treatment. This study also revealed that intratumoral metabolic heterogeneity plays an important role in the progression of different subtypes of breast cancer.

Creatine kinase B suppresses ferroptosis by phosphorylating GPX4 through a moonlighting function.

Activation of receptor protein kinases is prevalent in various cancers with unknown impact on ferroptosis. Here we demonstrated that AKT activated by insulin-like growth factor 1 receptor signalling phosphorylates creatine kinase B (CKB) T133, reduces metabolic activity of CKB and increases CKB binding to glutathione peroxidase 4 (GPX4). Importantly, CKB acts as a protein kinase and phosphorylates GPX4 S104. This phosphorylation prevents HSC70 binding to GPX4, thereby abrogating the GPX4 degradation regulated by chaperone-mediated autophagy, alleviating ferroptosis and promoting tumour growth in mice. In addition, the levels of GPX4 are positively correlated with the phosphorylation levels of CKB T133 and GPX4 S104 in human hepatocellular carcinoma specimens and associated with poor prognosis of patients with hepatocellular carcinoma. These findings reveal a critical mechanism by which tumour cells counteract ferroptosis by non-metabolic function of CKB-enhanced GPX4 stability and underscore the potential to target the protein kinase activity of CKB for cancer treatment.

[Distribution of tryptophan hydroxylase gene-T457C locus polymorphism in Han ethnic group in northern China].

OBJECTIVE: To study the distribution of the tryptophan hydroxylase (TPH) gene-T457C locus polymorphism in Han ethnic group in northern China and to find its applicable value in forensic science. METHODS: Genomic DNA samples, extracted from 180 unrelated individuals in northern Chinese Han population, were analyzed by PCR-RFLP. RESULTS: The discrimination power (DP) value and the power of exclusion (PE) value of the TPH gene-T457C locus were 0.624 and 0.187, respectively. The allele frequency showed significant difference from that of French people (P=0.04). CONCLUSION: Polymorphism of the TPH gene-T457C locus could show ethnic and regional differences. It has a potential to be used in forensic science.