Enhanced Lifetime of Cyanine Salts in Dilute Matrix Luminescent Solar Concentrators via Counterion Tuning.

Organic luminophores offer great potential for energy harvesting and light emission due to tunable spectral properties, strong luminescence, high solubility, and excellent wavelength-selectivity. To realize their full potential, the lifetimes of luminophores must extend to many years under illumination. Many organic luminophores, however, have a tendency to degrade and undergo rapid photobleaching, leading to the perception of intrinsic instability of organic molecules.

Pyruvate Kinase Activity Regulates Cystine Starvation Induced Ferroptosis through Malic Enzyme 1 in Pancreatic Cancer Cells.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with high mortality and limited efficacious therapeutic options. PDAC cells undergo metabolic alterations to survive within a nutrient-depleted tumor microenvironment. One critical metabolic shift in PDAC cells occurs through altered isoform expression of the glycolytic enzyme, pyruvate kinase (PK).

Adipocyte-derived kynurenine stimulates malignant transformation of mammary epithelial cells through the aryl hydrocarbon receptor.

Anti-hormone therapies are not efficacious for reducing the incidence of triple negative breast cancer (TNBC), which lacks both estrogen and progesterone receptors. While the etiology of this aggressive breast cancer subtype is unclear, visceral obesity is a strong risk factor for both pre- and post-menopausal cases. The mechanism by which excessive deposition of visceral adipose tissue (VAT) promotes the malignant transformation of hormone receptor-negative mammary epithelial cells is currently unknown.

The glutathione import system satisfies the Staphylococcus aureus nutrient sulfur requirement and promotes interspecies competition.

Sulfur is an indispensable element for bacterial proliferation. Prior studies demonstrated that the human pathogen Staphylococcus aureus utilizes glutathione (GSH) as a source of nutrient sulfur; however, mechanisms of GSH acquisition are not defined. Here, we identify a five-gene locus comprising a putative ABC-transporter and predicted γ-glutamyl transpeptidase (ggt) that promotes S.

Immunoediting instructs tumor metabolic reprogramming to support immune evasion.

Immunoediting sculpts immunogenicity and thwarts host anti-tumor responses in tumor cells during tumorigenesis; however, it remains unknown whether metabolic programming of tumor cells can be guided by immunosurveillance. Here, we report that T cell-mediated immunosurveillance in early-stage tumorigenesis instructs c-Myc upregulation and metabolic reprogramming in tumor cells. This previously unexplored tumor-immune interaction is controlled by non-canonical interferon gamma (IFNγ)-STAT3 signaling and supports tumor immune evasion.

Counterion Tuning of Near-Infrared Organic Salts Dictates Phototoxicity to Inhibit Tumor Growth.

Photodynamic therapy (PDT) has the potential to improve cancer treatment by providing dual selectivity through the use of both photoactive agent and light, with the goal of minimal harmful effects from either the agent or light alone. However, current PDT is limited by insufficient photosensitizers (PSs) that can suffer from low tissue penetration, insufficient phototoxicity (toxicity with light irradiation), or undesirable cytotoxicity (toxicity without light irradiation). Recently, we reported a platform for decoupling optical and electronic properties with counterions that modulate frontier molecular orbital levels of a photoactive ion.

Phosphorescent Metal Halide Nanoclusters for Tunable Photodynamic Therapy.

Photodynamic therapy (PDT) is currently limited by the inability of photosensitizers (PSs) to enter cancer cells and generate sufficient reactive oxygen species. Utilizing phosphorescent triplet states of novel PSs to generate singlet oxygen offers exciting possibilities for PDT. Here, we report phosphorescent octahedral molybdenum (Mo)-based nanoclusters (NC) with tunable toxicity for PDT of cancer cells without use of rare or toxic elements.

The Warburg effect: Saturation of mitochondrial NADH shuttles triggers aerobic lactate fermentation.

In this issue of Molecular Cell, Wang et al. investigate the Warburg effect in proliferating cells and demonstrate that lactate fermentation is a secondary mechanism activated after mitochondrial shuttles exceed their capacity to oxidize cytosolic NADH.

PHGDH heterogeneity potentiates cancer cell dissemination and metastasis.

Cancer metastasis requires the transient activation of cellular programs enabling dissemination and seeding in distant organs. Genetic, transcriptional and translational heterogeneity contributes to this dynamic process. Metabolic heterogeneity has also been observed, yet its role in cancer progression is less explored.

The mitochondrial pyruvate carrier regulates memory T cell differentiation and antitumor function.

Glycolysis, including both lactate fermentation and pyruvate oxidation, orchestrates CD8 T cell differentiation. However, how mitochondrial pyruvate metabolism and uptake controlled by the mitochondrial pyruvate carrier (MPC) impact T cell function and fate remains elusive. We found that genetic deletion of MPC drives CD8 T cell differentiation toward a memory phenotype.

Combined Plasma and Urinary Metabolomics Uncover Metabolic Perturbations Associated with Severe Respiratory Syncytial Viral Infection and Future Development of Asthma in Infant Patients.

A large percentage of infants develop viral bronchiolitis needing medical intervention and often develop further airway disease such as asthma. To characterize metabolic perturbations in acute respiratory syncytial viral (RSV) bronchiolitis, we compared metabolomic profiles of moderate and severe RSV patients versus sedation controls. RSV patients were classified as moderate or severe based on the need for invasive mechanical ventilation.

Loss of Health Promoting Bacteria in the Gastrointestinal Microbiome of PICU Infants with Bronchiolitis: A Single-Center Feasibility Study.

The feasibility of gastrointestinal (GI) microbiome work in a pediatric intensive care unit (PICU) to determine the GI microbiota composition of infants as compared to control infants from the same hospital was investigated. In a single-site observational study at an urban quaternary care children's hospital in Western Michigan, subjects less than 6 months of age, admitted to the PICU with severe respiratory syncytial virus (RSV) bronchiolitis, were compared to similarly aged control subjects undergoing procedural sedation in the outpatient department. GI microbiome samples were collected at admission ( = 20) and 72 h ( = 19) or at time of sedation ( = 10).

Current Advances in Photoactive Agents for Cancer Imaging and Therapy.

Photoactive agents are promising complements for both early diagnosis and targeted treatment of cancer. The dual combination of diagnostics and therapeutics is known as theranostics. Photoactive theranostic agents are activated by a specific wavelength of light and emit another wavelength, which can be detected for imaging tumors, used to generate reactive oxygen species for ablating tumors, or both.

Balancing precision versus cohort transcriptomic analysis of acute and recovery phase of viral bronchiolitis.

Viral infections affecting the lower respiratory tract place enormous burdens on hospitals. As neither vaccines nor antiviral agents exist for many viruses, understanding risk factors and outcomes in each patient using minimally invasive analysis, such as blood, can lead to improved health care delivery. A cohort of PAXgene RNA sequencing of infants admitted with moderate or severe acute bronchiolitis and respiratory syncytial virus were compared with case-control statistical analysis and cohort-based outlier mapping for precision transcriptomics.

In Vivo Evidence for Serine Biosynthesis-Defined Sensitivity of Lung Metastasis, but Not of Primary Breast Tumors, to mTORC1 Inhibition.

In tumors, nutrient availability and metabolism are known to be important modulators of growth signaling. However, it remains elusive whether cancer cells that are growing out in the metastatic niche rely on the same nutrients and metabolic pathways to activate growth signaling as cancer cells within the primary tumor. We discovered that breast-cancer-derived lung metastases, but not the corresponding primary breast tumors, use the serine biosynthesis pathway to support mTORC1 growth signaling.

Targeting Subtype-Specific Metabolic Preferences in Nucleotide Biosynthesis Inhibits Tumor Growth in a Breast Cancer Model.

Investigating metabolic rewiring in cancer can lead to the discovery of new treatment strategies for breast cancer subtypes that currently lack targeted therapies. In this study, we used MMTV-Myc-driven tumors to model breast cancer heterogeneity, investigating the metabolic differences between two histologic subtypes, the epithelial-mesenchymal transition (EMT) and the papillary subtypes. A combination of genomic and metabolomic techniques identified differences in nucleotide metabolism between EMT and papillary subtypes.

DNA Methylation and Gene Expression with Clinical Covariates Explain Variation in Aggressiveness and Survival of Pancreatic Cancer Patients.

Pancreatic cancer (PC) is associated with a high mortality rate. We explored the interindividual variation of cancer outcomes, attributable to DNA methylation, gene expression, and clinical factors among PC patients. We aim to determine whether we could differentiate subjects with greater nodal involvement, higher cancer staging, and subsequent survival.

UDP-glucose 6-dehydrogenase knockout impairs migration and decreases in vivo metastatic ability of breast cancer cells.

Dysregulated metabolism is a hallmark of cancer that supports tumor growth and metastasis. One understudied aspect of cancer metabolism is altered nucleotide sugar biosynthesis, which drives aberrant cell surface glycosylation known to support various aspects of cancer cell behavior including migration and signaling. We examined clinical association of nucleotide sugar pathway gene expression and found that UGDH, encoding UDP-glucose 6-dehydrogenase which catalyzes production of UDP-glucuronate, is associated with worse breast cancer patient survival.

Metabolomic profiling of mouse mammary tumor-derived cell lines reveals targeted therapy options for cancer subtypes.

Purpose: Breast cancer is a heterogeneous disease with several subtypes that currently do not have targeted therapeutic options. Metabolomics has the potential to uncover novel targeted treatment strategies by identifying metabolic pathways required for cancer cells to survive and proliferate.

Methods: The metabolic profiles of two histologically distinct breast cancer subtypes from a MMTV-Myc mouse model, epithelial-mesenchymal-transition (EMT) and papillary, were investigated using mass spectrometry-based metabolomics methods.

Dynamic ROS Regulation by TIGAR: Balancing Anti-cancer and Pro-metastasis Effects.

The role of ROS in cancer is complex, with studies demonstrating both pro- and anti-tumor effects. In a pancreatic ductal adenocarcinoma model, ROS limitation through TIGAR has been shown to initially support cancer development but to later become a metabolic liability in metastasizing cells that is counteracted by decreased TIGAR expression.

Cysteine catabolism and the serine biosynthesis pathway support pyruvate production during pyruvate kinase knockdown in pancreatic cancer cells.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options. Pyruvate kinase, especially the M2 isoform (PKM2), is highly expressed in PDAC cells, but its role in pancreatic cancer remains controversial. To investigate the role of pyruvate kinase in pancreatic cancer, we knocked down PKM2 individually as well as both PKM1 and PKM2 concurrently (PKM1/2) in cell lines derived from a pancreatic mouse model.

Mitochondrial Haplotype of the Host Stromal Microenvironment Alters Metastasis in a Non-cell Autonomous Manner.

Mitochondria contribute to tumor growth through multiple metabolic pathways, regulation of extracellular pH, calcium signaling, and apoptosis. Using the Mitochondrial Nuclear Exchange (MNX) mouse models, which pair nuclear genomes with different mitochondrial genomes, we previously showed that mitochondrial SNPs regulate mammary carcinoma tumorigenicity and metastatic potential in genetic crosses. Here, we tested the hypothesis that polymorphisms in stroma significantly affect tumorigenicity and experimental lung metastasis.