RSPO2-associated mitochondrial metabolism defines molecular subtypes with distinct clinical and immune features in esophageal cancer.

Background: Esophageal cancer is a highly aggressive malignancy with limited treatment options and poor prognosis. The identification of novel molecular subtypes and therapeutic targets is crucial for improving clinical outcomes.

Method: In this study, we investigated the role of R-spondin 2 (RSPO2) in esophageal cancer and its association with mitochondrial metabolism.

Propulsive cell entry diverts pathogens from immune degradation by remodeling the phagocytic synapse.

Phagocytosis is a critical immune function for infection control and tissue homeostasis. During phagocytosis, pathogens are internalized and degraded in phagolysosomes. For pathogens that evade immune degradation, the prevailing view is that virulence factors are required to disrupt the biogenesis of phagolysosomes.

Timing of Phagosome Maturation Depends on Their Transport Switching from Actin to Microtubule Tracks.

Phagosomes, specialized membrane compartments responsible for digesting internalized pathogens, undergo sequential dynamic and biochemical changes as they mature from nascent phagosomes to degradative phagolysosomes. Maturation of phagosomes depends on their transport along actin filaments and microtubules. However, the specific quantitative relationship between the biochemical transformation and transport dynamics remains poorly characterized.

Propulsive cell entry diverts pathogens from immune degradation by remodeling the phagocytic synapse.

Phagocytosis is a critical immune function for infection control and tissue homeostasis. This process is typically described as non-moving pathogens being internalized and degraded in phagolysosomes. For pathogens that evade immune degradation, the prevailing view is that virulence factors that biochemically disrupt the biogenesis of phagoslysosomes are required.

Advancing cell-based cancer immunotherapy through stem cell engineering.

Advances in cell-based therapy, particularly CAR-T cell therapy, have transformed the treatment of hematological malignancies. Although an important step forward for the field, autologous CAR-T therapies are hindered by high costs, manufacturing challenges, and limited efficacy against solid tumors. With ongoing progress in gene editing and culture techniques, engineered stem cells and their application in cell therapy are poised to address some of these challenges.

Kinetics of phagosome maturation is coupled to their intracellular motility.

Immune cells degrade internalized pathogens in phagosomes through sequential biochemical changes. The degradation must be fast enough for effective infection control. The presumption is that each phagosome degrades cargos autonomously with a distinct but stochastic kinetic rate.

Targeting Immunosuppressive Tumor-Associated Macrophages Using Innate T Cells for Enhanced Antitumor Reactivity.

The field of T cell-based and chimeric antigen receptor (CAR)-engineered T (CAR-T) cell-based antitumor immunotherapy has seen substantial developments in the past decade; however, considerable issues, such as graft-versus-host disease (GvHD) and tumor-associated immunosuppression, have proven to be substantial roadblocks to widespread adoption and implementation. Recent developments in innate immune cell-based CAR therapy have opened several doors for the expansion of this therapy, especially as it relates to allogeneic cell sources and solid tumor infiltration. This study establishes in vitro killing assays to examine the TAM-targeting efficacy of MAIT, iNKT, and γδT cells.

An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation of Cancer Immunotherapy.

Tumor-associated macrophages (TAMs) accumulate in the solid tumor microenvironment (TME) and have been shown to promote tumor growth and dampen antitumor immune responses. TAM-mediated suppression of T-cell antitumor reactivity is considered to be a major obstacle for many immunotherapies, including immune checkpoint blockade and adoptive T/CAR-T-cell therapies. An ex vivo culture system closely mimicking the TME can greatly facilitate the study of cancer immunotherapies.

Minimally Invasive Preclinical Monitoring of the Peritoneal Cavity Tumor Microenvironment.

Intraperitoneal (i.p.) experimental models in mice can recapitulate the process of i.

Anisotropic presentation of ligands on cargos modulates degradative function of phagosomes.

Anisotropic arrangement of cell wall components is ubiquitous among bacteria and fungi, but how such functional anisotropy affects interactions between microbes and host immune cells is not known. Here we address this question with regard to phagosome maturation, the process used by host immune cells to degrade internalized microbes. We developed two-faced microparticles as model pathogens that display ligands on only one hemisphere and simultaneously function as fluorogenic sensors for probing biochemical reactions inside phagosomes during degradation.

A novel DNA methylation signature associated with lymph node metastasis status in early gastric cancer.

Background: Lymph node metastasis (LNM) is an important factor for both treatment and prognosis of early gastric cancer (EGC). Current methods are insufficient to evaluate LNM in EGC due to suboptimal accuracy. Herein, we aim to identify methylation signatures for LNM of EGC, facilitate precision diagnosis, and guide treatment modalities.

Single-phagosome imaging reveals that homotypic fusion impairs phagosome degradative function.

Immune cells degrade internalized pathogens in vesicle compartments called phagosomes. Many intracellular bacteria induce homotypic phagosome fusion to survive in host cells, but the fusion interaction between phagosomes and its consequence for phagosome function have scarcely been studied. Here, we characterize homotypic fusion between phagosomes in macrophages and identify how such interactions impact the degradative capacity of phagosomes.

A urine-based DNA methylation assay to facilitate early detection and risk stratification of bladder cancer.

Background: Current non-invasive tests have limited sensitivities and lack capabilities of pre-operative risk stratification for bladder cancer (BC) diagnosis. We aimed to develop and validate a urine-based DNA methylation assay as a clinically feasible test for improving BC detection and enabling pre-operative risk stratifications.

Methods: A urine-based DNA methylation assay was developed and validated by retrospective single-center studies in patients of suspected BC in Cohort 1 (n = 192) and Cohort 2 (n = 98), respectively.

Identifying potential DNA methylation markers in early-stage colorectal Cancer.

Colorectal cancer (CRC) is the second leading malignancy worldwide. Accurate screening is pivotal to early CRC detection, yet current screening modality involves invasive colonoscopy while non-invasive FIT tests have limited sensitivity. We applied a DNA methylation assay to identify biomarkers for early-stage CRC detection, risk stratification and precancerous lesion screening at tissue level.

Loss of GATA6 expression promotes lymphatic metastasis in bladder cancer.

Lymph node metastasis is associated with tumor relapse and poor patient prognosis in bladder cancer. However, the mechanisms by which bladder carcinoma cells induce lymphangiogenesis and further promote metastasis in the lymphatic system remain unclear. Here, we show that the transcription factor GATA-binding factor 6 (GATA6) was substantially downregulated in bladder cancer via promoter hypermethylation.

Tracking Single Molecules in Biomembranes: Is Seeing Always Believing?

The spatial organization of molecules in cell membranes and their dynamic interactions play a central role in regulating cell functions. Single-particle tracking (SPT), a technique in which single molecules are imaged and tracked in real time, has led to breakthrough discoveries regarding these spatiotemporal complexities of cell membranes. There are, however, emerging concerns about factors that might produce misleading interpretations of SPT results.

"Waltz" of Cell Membrane-Coated Nanoparticles on Lipid Bilayers: Tracking Single Particle Rotation in Ligand-Receptor Binding.

Understanding the binding of nanoparticles to receptors on biomembranes is critical to the development and screening of therapeutic materials. A prevailing understanding is that multivalent ligand-receptor binding leads to slower and confined translational motion of nanoparticles. In contrast, we report in this study distinct types of rotational dynamics of nanoparticles during their seemingly similar translational confinements in ligand-receptor binding.

Cargos Rotate at Microtubule Intersections during Intracellular Trafficking.

Intracellular cargos are transported by molecular motors along actin and microtubules, but how their dynamics depends on the complex structure of the cytoskeletal network remains unclear. In this study, we investigated this longstanding question by measuring simultaneously the rotational and translational dynamics of cargos at microtubule intersections in living cells. We engineered two-faced particles that are fluorescent on one hemisphere and opaque on the other and used their optical anisotropy to report the rotation of cargos.

Single-Janus Rod Tracking Reveals the "Rock-and-Roll" of Endosomes in Living Cells.

Endosomes in cells are known to move directionally along microtubules, but their rotational dynamics have rarely been investigated. Even less is known, specifically, about the rotation of nonspherical endosomes. Here we report a single-Janus rod rotational tracking study to reveal the rich rotational dynamics of rod-shaped endosomes in living cells.

Seeing the unseen: Imaging rotation in cells with designer anisotropic particles.

Cellular functions are enabled by cascades of transient biological events. Imaging and tracking the dynamics of these events have proven to be a powerful means of understanding the principles of cellular processes. These studies have typically focused on translational dynamics.