Browse Articles

Harnessing macrophage-drug conjugates for allogeneic cell-based therapy of solid tumors via the TRAIN mechanism

Abstract Treatment of solid tumors remains challenging and therapeutic strategies require continuous development. Tumor-infiltrating macrophages play a pivotal role in tumor dynamics. Here, we present a Macrophage-Drug Conjugate (MDC) platform technology that enables loading macrophages with ferritin-drug complexes. We first show that macrophages actively take up human heavy chain ferritin (HFt) in vitro via macrophage scavenger receptor 1 (MSR1). We further manifest that drug-loaded macrophages transfer ferritin to adjacent cancer cells through a process termed ‘TRAnsfer of Iron-binding protein’ (TRAIN). The TRAIN process requires direct cell-to-cell contact and an immune synapse-like structure. At last, MDCs with various anti-cancer drugs are formulated with their safety and anti-tumor efficacy validated in multiple syngeneic mice and orthotopic human tumor models via different routes of administration. Importantly, MDCs can be prepared in advance and used as thawed products, supporting their clinical applicability. This MDC approach thus represents a promising advancement in the therapeutic landscape for solid tumors.

Author Correction: Self-other distinction modulates the sense of self-agency during joint actions

Dendritic excitations govern back-propagation via a spike-rate accelerometer

The corpus callosum in people with congenital adrenal hyperplasia (CAH)

Abstract Congenital Adrenal Hyperplasia (CAH) is a group of genetic disorders that affect the adrenal glands. CAH manifests in abnormal levels of cortisol and androgens and is accompanied by white matter alterations. However, no CAH study has specifically targeted the corpus callosum, the brain’s largest white matter fiber tract. To bridge that gap in the literature, we investigated callosal morphology in 53 individuals with CAH and 53 matched controls (66 women, 40 men). In addition to calculating areas for seven callosal subsections, we estimated the callosal thickness at 100 equidistant points. All statistical analyses were conducted while co-varying for age and total brain volume and applying corrections for multiple comparisons. There were no significant effects of biological sex and no significant group-by-sex interactions. However, there was a significant effect of group, both for area measures and thickness estimates, indicating smaller dimensions within the callosal splenium and isthmus in people with CAH. Our findings corroborate previous studies highlighting white matter alterations in CAH and may suggest that callosal integrity is compromised due to potentially adverse effects of glucocorticoids, a standard treatment for both men and women with CAH.

Spatially mapping the tumour immune microenvironments of non-small cell lung cancer

Magnetic susceptibility components reveal different aspects of neurodegeneration in alpha-synucleinopathies

Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signalling

Ultra-processed foods and plant-based alternatives impair nutritional quality of omnivorous and plant-forward dietary patterns in college students

Abstract The health benefits of a plant-based diet may be outweighed by an increased consumption of ultra-processed foods (UPF) and plant-based alternatives. This study compares diet quality (intakes of protein, saturated fatty acids, sugar, fiber, and micronutrients) and nutritional status (prevalence of low holotranscobalamin and ferritin levels) among different dietary patterns: 22.5% vegans, 46.5% vegetarians, 31% omnivores in 142 first-year college students (20 ± 1.6 years, BMI 21.9 ± 3.1 kg/m², 83% female). Intakes of vitamin B12, folate, iron, zinc, and calcium were on average below reference values, especially in vegans and vegetarians. However, the prevalence of low holotranscobalamin and ferritin levels did not differ between the dietary groups, presumably due to supplementation. Irrespective of the diet, UPF contributed to 49% of daily energy intake. UPF exhibited a lower content of protein, fiber, vitamin B2, vitamin B12, folate, zinc and calcium compared to processed foods (all p < 0.001). Plant-based alternatives contained more fiber and less saturated fatty acids whereas the content of protein and micronutrients was lower compared with animal products (all p < 0.05). In conclusion, UPF consumption contributes to the inadequate intake of many micronutrients by young adults. This is further aggravated by plant-forward eating patterns including the consumption of plant-based alternatives.

Multi-locus CRISPRi targeting with a single truncated guide RNA

Feasibility and safety of zero-fluoro, “apron-less” approach to repeat pulmonary vein isolation procedures using radiofrequency energy after initial cryoballoon ablation

Non-canonical lysosomal lipolysis drives mobilization of adipose tissue energy stores with fasting

Relationship between age and delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage requiring invasive mechanical ventilation: a secondary analysis

Structural basis for RNA-guided DNA degradation by Cas5-HNH/Cascade complex

Elevated POSTN expression predicts poor prognosis and is associated with radioresistance in cervical cancer patients treated with radical radiotherapy

Electricity- and hydrogen-driven energy system sector-coupling in net-zero CO2 emission pathways

The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics

Abstract The glucocorticoid receptor (GR) plays a significant role in breast cancer cell behaviour, although data on its effects are conflicting. The impact of GR agonist dexamethasone (dex) and antagonist mifepristone (mif) on oestrogen-positive (ER+) and triple-negative (TN) breast cancer cell lines in both 2D and 3D cultures was studied using multiple in vitro functional assays and transcriptome sequencing. GR activation increased cell motility in TN but not in ER + tumour cells, as observed in both collective and single-cell migration tests. Time-lapse analysis showed enhanced motility after 4–6 h in wound healing, despite dex inhibiting migration initially. This inhibition was observed at 2 h in single-cell tracking migration assays. Cell proliferation increased in TN and decreased in ER + cells upon GR activation, reversed by GR antagonist. RNA sequencing revealed dex’s impact on cell adhesion and extracellular matrix signalling in TN cells and on DNA replication in ER + cells. Based on data from 1085 human breast cancer specimens, GR pathway expression correlated with migratory, extracellular matrix, and angiogenesis gene signatures. Additionally, higher expression of GR and increased GR signature were observed in fast-migrating cells compared to slow-migrating ones. Positive correlation between the GR signature and migration signature at the single-cell level indicated an association between GR activity and cell migration. For the first time, we assessed altered time-lapse migration dynamics in TN breast cancer cells, potentially contributing to cancer progression and prognosis, highlighting that the effects of dexamethasone on breast cancer cell migration are influenced by ER status and treatment duration.

Human mobility is well described by closed-form gravity-like models learned automatically from data

Differential expression of CD175 and CA19-9 in pancreatic adenocarcinoma

Targeting ceramide transfer protein sensitizes AML to FLT3 inhibitors via a GRP78-ATF6-CHOP axis

Clinical benefits of the 5th intercostal incision in uniportal VATS for female patients