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Developmental Cell

Cancer stem cell plasticity and tumor hierarchy👇

✅Hierarchical tumor organization Tumors are organized in a hierarchical manner, with cancer stem cells (CSCs) positioned at the apex. CSCs possess long-term self-renewal capacity and generate diverse progeny, sustaining tumor growth and cellular heterogeneity.

✅Self-renewal and differentiation CSCs can undergo self-renewal to maintain the stem cell pool or differentiate into multiple cancer cell lineages. These differentiated cells form the bulk of the tumor and display varying functional and phenotypic states.

✅Cell plasticity and dedifferentiation Differentiated cancer cells are not irreversibly committed. Through cellular plasticity, they can dedifferentiate back into CSCs, often via processes such as epithelial–mesenchymal transition (EMT), restoring stem-like properties.

✅Interconversion of CSC states Distinct CSC subpopulations can transition between different stemness states. This dynamic interconversion enhances tumor adaptability and contributes to therapy resistance and disease progression.

✅Biological and clinical relevance The combination of hierarchy and plasticity allows tumors to regenerate after treatment and maintain intratumoral diversity. Targeting both CSCs and the mechanisms that enable plasticity is therefore critical for effective cancer therapy.

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Chrono-Immune Neuropathy During PD-1 Blockade: A Report of a Fatal Case and Hypothesis on Circadian Modulation of Neurotoxicity

Immune checkpoint inhibitors can cause a wide spectrum of immune-related adverse events, including rare but severe neurological complications. This report describes a fatal case of progressive immune-mediated neuropathy in a melanoma patient treated with PD-1 blockade, in whom worsening neuropathic pain and functional decline coincided with irregular, non-aligned timing of immunotherapy infusions. PET-CT imaging, MRI, and laboratory testing excluded metastatic, infectious, metabolic, and paraneoplastic causes. Longitudinal evaluation revealed fluctuations in inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), with peaks occurring shortly after late-afternoon infusions. Earlier infusions were associated with fewer symptoms.

A molecular gatekeeper that controls protein synthesis

Current smoking was linked to a higher risk for all-cause dementia, especially vascular dementia, with the strongest effects seen in those younger than 85 years and women. It was not significantly associated with the risk for Alzheimer’s dementia. Former smoking was associated with an increased risk for vascular dementia only in men, particularly those younger than 85 years.


Current smoking is associated with an elevated risk for all-cause dementia, particularly vascular dementia, with the strongest associations seen in participants younger than 85 years.

Parkinson Disease SNCA Risk Variants Are Associated With Higher Asymmetric Putamen Dopaminergic Dysfunction

This study assessed the endophenotypic potential of striatal dopamine transporter uptake in carriers of Parkinson disease–associated SNCA genetic risk variants.


ObjectivesThe aim of this study was to investigate the endophenotypic potential of striatal dopamine transporter (DAT) uptake in carriers of Parkinson disease (PD)–associated SNCA genetic risk variants. MethodsWe analyzed 381 patients with de novo PD from the Parkinson’s Progression Markers Initiative (PPMI). The genotype of previously identified PD-related SNCA risk variants was extracted and used to compute an individual PD-specific SNCA genetic risk score (GRS). Striatal DAT uptake was quantified using 123 I‐FP‐CIT SPECT and assessed at baseline and 24-month follow-up. Mixed models were applied to explore the relationship between striatal 123 I‐FP‐CIT SPECT specific binding ratios (SBRs) and PD SNCA risk variants.

‘Don’t use them’: Tanning beds triple skin cancer risk, study finds

When Heidi Tarr was a teenager, she used a tanning bed several times a week with her friends because they all wanted to glow like a celebrity.

“It was just the thing to do—everyone wanted that nice, dark, tan skin,” the 49-year-old market researcher told AFP via video call from Chicago.

Then one day in her 30s, Tarr noticed a strange mole on her back.

Butyrolactol A enhances caspofungin efficacy via flippase inhibition in drug-resistant fungi

Chen et al. identify the natural product butyrolactol A as an inhibitor of the phospholipid flippase Apt1-Cdc50, which it locks in a nonfunctional state. By disrupting membrane homeostasis and enhancing drug uptake, butyrolactol A restores echinocandin efficacy against intrinsically resistant fungal pathogens, including Cryptococcus and Candida auris.

Injury and inflammation promote cancer progression at the anorectal junction

Petitpas et al. dissect the single-cell transcriptome underlying the sequential steps of pre-malignant lesions and early anorectal cancer, mimicking disease evolution seen in patients, at the epithelial and immune level. They reveal a key epithelial-immune cell crosstalk involving IL-17-producing T lymphocytes and neutrophils as essential for the dysplasia-carcinoma progression.

Electromagnetic wireless remote control of mammalian transgene expression

An intriguing paper by Lin et al. where cells were engineered to express a signaling pathway that transcribes a gene of interest upon generation of reactive oxygen species (ROS) by CBCFO nanoparticles in response to applied electromagnetic fields. When implanted in a mouse model of diabetes, nanoparticle-treated genetically engineered cells produced insulin and decreased blood glucose levels in the mice after electromagnetic field application.


Wireless magnetic control of gene expression in mammalian cells has been developed based on intracellular nanointerface and ROS-mediated signalling. The approach allows remotely tunable insulin release and regulates blood glucose in diabetic mice.

Brain Discovery Reveals a Potential New Way To Treat Dementia

Increasing the levels of a particular phospholipid in the membranes of brain cells may offer a promising new way to improve blood circulation in the brain and support healthier brain activity. A potential new approach to treating reduced blood flow in the brain and related forms of dementia is be

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