T cells targeting a KRAS mutation can induce durable tumor regression in some patients with metastatic epithelial cancer. It is unknown whether T cells targeting mutant KRAS that are capable of killing tumor cells can be identified from peripheral blood of patients with pancreatic cancer. We developed an in vitro stimulation approach and identified HLA-A*11:01-restricted KRAS G12V-reactive CD8+ T cells and HLA-DRB1*15:01-restricted KRAS G12V-reactive CD4+ T cells from peripheral blood of 2 out of 6 HLA-A*11:01-positive patients with pancreatic cancer whose tumors expressed KRAS G12V.
View Article and Find Full Text PDFMacromol Rapid Commun
January 2025
The increasing prevalence of antibiotic resistance, driven by the overuse and misuse of conventional antibiotics, has become a critical public health concern. Photothermal antibacterial therapy (PTAT) utilizes heat generated by photothermal agents under light exposure to inhibit bacterial growth without inducing resistance, attracting more and more attention. Quinoid conjugated polymers, especially para-azaquinodimethane (AQM) polymer, are a class of organic semiconductors known for efficient π-electron delocalization, near-infrared absorption, and narrow bandgap, showing great potential in the application of photothermal reagents.
View Article and Find Full Text PDFOrganoid technology provides a transformative approach to understand human physiology and pathology, offering valuable insights for scientific research and therapeutic development. Human gastric organoids, in particular, have gained significant interest for applications in disease modeling, drug discovery, and studies of tissue regeneration and homeostasis. However, the lack of standardized quality control has limited their extensive clinical applications.
View Article and Find Full Text PDFMembers of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.
View Article and Find Full Text PDFGastric cancer is one of the most common malignancies with poor prognosis. The use of organoids to simulate gastric cancer has rapidly developed over the past several years. Patient-derived gastric cancer organoids serve as in vitro models that closely mimics donor characteristics, offering new opportunities for both basic and applied research.
View Article and Find Full Text PDFPancreatic ductal adenocarcinoma (PDAC) has an atypical, highly stromal tumour microenvironment (TME) that profoundly contributes to its poor prognosis. Here, to better understand the intercellular signalling between cancer and stromal cells directly in PDAC tumours, we developed a multidimensional proteomic strategy called TMEPro. We applied TMEPro to profile the glycosylated secreted and plasma membrane proteome of 100 human pancreatic tissue samples to a great depth, define cell type origins and identify potential paracrine cross-talk, especially that mediated through tyrosine phosphorylation.
View Article and Find Full Text PDFRadiotherapy has been demonstrated to be one of the most significant treatments for cervical cancer, during which accurate and efficient delineation of target volumes is critical. To alleviate the data demand of deep learning and promote the establishment and promotion of auto-segmentation models in small and medium-sized oncology departments and single centres, we proposed an auto-segmentation algorithm to determine the cervical cancer target volume in small samples based on multi-decoder and semi-supervised learning (MDSSL), and we evaluated the accuracy via an independent test cohort. In this study, we retrospectively collected computed tomography (CT) datasets from 71 pelvic cervical cancer patients, and a 3:4 ratio was used for the training and testing sets.
View Article and Find Full Text PDFIt is said that all models are wrong, but some are useful. In vitro human cell-based models are a prime example of this maxim. We asked researchers: when is your model system useful? How can it be made more useful? What are its limitations?
View Article and Find Full Text PDFObjectives: To explore the effects of different test positions on quantitative muscle strength of wrist and finger flexor muscle groups and to establish a standardized muscle strength test protocol for each muscle group.
Methods: Forty healthy subjects (12 males and 28 females) were recruited. A portable digital quantitative muscle strength tester, Micro FET2, was used to measure the flexor muscle strength of each finger and the wrist joint at the 30° extension, 0° neutral, and 30° flexion, respectively.
Organ development, regeneration and cancer initiation are typically influenced by the proliferation and lineage plasticity of tissue-specific stem cells. Prostate intermediate cells, which exhibit characteristics of both basal and luminal cells, are prevalent in pathological states and during organ development. However, the identity, fate and function of these intermediate cells in prostate development are not well understood.
View Article and Find Full Text PDFSurface condensation control strategies are crucial but commonly require relatively tedious, time-consuming, and expensive techniques for surface-chemical and topographical engineering. Here we report a strategy to alter surface condensation behavior without resorting to any molecule-type or topographical transmutations. After ultrafast contact of liquids with and removal from surfaces, the condensation rate and density of water droplets on the surfaces decrease, the extent of which is positively correlated with the polarity of the liquid and the duration of contact.
View Article and Find Full Text PDFSex differences in mammalian complex traits are prevalent and are intimately associated with androgens. However, a molecular and cellular profile of sex differences and their modulation by androgens is still lacking. Here we constructed a high-dimensional single-cell transcriptomic atlas comprising over 2.
View Article and Find Full Text PDFVirtual reality (VR)-based mindfulness is a promising method to improve the health of older adults. Therefore, many attempts have been made to explore the application of VR-based mindfulness, such as VR meditation and mind-body exercises, in older adults. Generally, current studies indicate the heavy reliance on apparatus for implementing VR-based mindfulness interventions.
View Article and Find Full Text PDFIn this study, we discuss the tunability of valley splitting using first-principles calculations with a monolayer MoTe and layered ferromagnetic MnS heterostructure as an example. We observe that, due to the magnetic proximity effect (MPE) at the interface, a monolayer of MoTe can exhibit a significant valley splitting of 55.2 meV.
View Article and Find Full Text PDFPancreatic ductal adenocarcinoma (PDAC) accounts for 95% of all pancreatic cancer cases, posing grave challenges to its diagnosis and treatment. Timely diagnosis is pivotal for improving patient survival, necessitating the discovery of precise biomarkers. An innovative approach was introduced to identify gene markers for precision PDAC detection.
View Article and Find Full Text PDFRaman spectroscopy has found widespread usage in monitoring cell culture processes both in research and practical applications. However, commonly, preprocessing methods, spectral regions, and modeling parameters have been chosen based on experience or trial-and-error strategies. These choices can significantly impact the performance of the models.
View Article and Find Full Text PDFThe extracellular matrix (ECM) orchestrates cell behavior and tissue regeneration by modulating biochemical and mechanical signals. Manipulating cell-material interactions is crucial for leveraging biomaterials to regulate cell functions. Yet, integrating multiple cues in a single material remains a challenge.
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