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The efficacy of CAR-T cells against solid tumors is still limited by immunosuppressive factors. Here, the authors show that engineering of CAR T cells with A1R enhances their efficacy against solid tumors in vitro and in vivo.

Drug resistance remains a major challenge in cancer treatment. Here, the authors identify Connexin43 as target that enhances BRAF/MEKi efficacy by interfering with DNA repair pathways, overcoming drug resistance. They develop an mRNA therapy that improves efficacy and sensitizes resistant cells.

There are currently no licensed vaccines to prevent Group A Streptococcus (GAS) infections. In this study, the authors evaluate the immune response and preclinical efficacy of a multicomponent mRNA lipid-nanoparticle vaccine against GAS.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

High-content protein arrays were used to identify cysteine dioxygenase (CDO1) as a small-molecule glue target for the von Hippel–Lindau (VHL) E3 ubiquitin ligase and induces VHL-dependent proteasomal degradation of CDO1 in cells.

This study identifies SCEP3 as a conserved central element of the plant synaptonemal complex. SCEP3 is critical for synapsis, heterochiasmy and crossover interference. SCEP3 also promotes a subset of crossover events.

Our understanding of the mechanisms underlying the role and regulation of photorespiration in plant response to high light is still limited. Here, the authors report a cytosolic glyoxylate shunt for photorespiration that can reduce carbon retention in the photorespiratory intermediates that are toxic to plants.

Producing mature epicardium in vitro could allow better understanding of cardiac tissue regeneration. Here, the authors describe how inhibition of mTOR signaling during differentiation of induced pluripotent stem cells yields mature epicardium that can be used to model adult epicardial reactivation.

Technology research is the driving force of the innovations that shape the world. Sony Group Corporation (Sony) and Nature partnered together to launch the Sony Women in Technology Award to recognize three outstanding early to mid-career researchers from the field of technology. Here, we interviewed the winners of the inaugural 2024 award on the inspirations behind their outstanding research.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

Analyzing readouts of inflammaging across four cohorts, Franck and colleagues identify strong variation and observe that inflammaging, in its known form, primarily emerges in industrialized—but not nonindustrialized—populations.

The human kidney maintains homeostasis through a complex network of up to a million nephrons. Here the authors construct a 3D neuro-nephron connectivity map of human kidneys, which reveals neuro-glomerular communities across the kidney connected via “mother glomeruli” as hub points explaining structural basis for fluid homeostasis. These networks develop after birth and decline with age and in disease states

In mice, prolonged consumption of a high-fat diet decreases interest in calorie-rich foods as a result of reduced neurotensin expression and signalling, which uncouples hedonic feeding behaviour linked to neurons projecting from lateral nucleus accumbens to ventral tegmental area.

Bellaart et al. address how the ubiquitin ligase tripartite motif-containing protein 37, the gene for which is mutated in Mulibrey nanism, uses peptide motif recognition and substrate-directed oligomerization to prevent the formation of ectopic spindle poles that cause chromosome missegregation.

Transplantation of allogeneic hematopoietic stem cells (HSCs) is the only reported cure of HIV-1. Here, authors describe an autologous HSC transplant therapy with cells engineered for multilayered resistance to HIV-1 through CCR5 knockout and secretion of HIV inhibiting antibodies by B cell progeny.

Rhine et al. find that neuronal aging leads to widespread dysregulation of RNA biology, including mislocalization of splicing proteins like TDP-43, chronic cellular stress and reduced resiliency.

An analysis of genomic, molecular and neuroanatomical traits across extant primates reveals early divergence in visual and olfactory systems of major primate lineages consistent with lineage-specific shifts in diel activity and dietary niche, providing support for a sensory ‘reallocation’ hypothesis.

Successful skeletal muscle regeneration involves a complex and finely tuned inter-cellular response. Here, by using spatial transcriptomics, the authors identify an intercellular communication axis between fibro-adipogenic progenitors and macrophages to enhance macrophage-mediated tissue repair.

This study uncovered genetic associations with environmental sensitivity in psychiatric and neurodevelopmental traits in an international collaboration using data from more than 21,000 monozygotic twins—the largest genetic study of monozygotic twin differences to date.

Cave ecologist Fernando Calderón Gutiérrez is studying the resilience of cave-adapted species in the face of climate change and other stressors.

Heo, Xu et al. used comprehensive plasma proteomics to identify 416 plasma proteins (294 new) associated with Alzheimer’s disease and applied machine learning to select 7 proteins that were highly predictive of Alzheimer’s disease across multiple cohorts.

Distinct hippocampal feedback pathways to deep and superficial layers of the cortex in mice differentially modulate excitation–inhibition dynamics, plasticity and cognitive behavioral output.

This paper highlights the far-red chemigenetic H₂O₂ reporter oROS-HT₆₃₅, which enables detailed insights into intricate intracellular and intercellular H₂O₂ dynamics, along with their environmental interactants, through spatially resolved, multiplexed real-time H₂O₂ imaging.

This study identifies cycling mRNAs, miRNAs, gene networks and mRNA-miRNA co-expression pairs in the cortex, hypothalamus, and corpus striatum, providing a searchable catalogue to help refine future analyses of the CNS.

Alamos et al. show that Agrobacterium engages in density-dependent interactions that dictate transformation efficiency and transgene expression. These findings enable a quantitative model to improve metabolic engineering in a predictive manner.

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that PLpro inhibition may be a viable strategy for preventing and treating long COVID.

Next generation precision lysine-specific histone demethylase 1A (LSD1) covalent inhibitors which selectively block LSD1 enzyme activity by forming a compact N-formyl-FAD adduct have been developed, but the mechanism of adduct formation was unclear. Here, the authors show that the covalent inhibitor-FAD adduct undergoes a Grob fragmentation and elucidate the structure-activity relationships that promote this transformation.

We present a versatile correlative light and electron microscopy protocol for visualizing the ultrastructural details found in brain samples and for revealing previously undescribed features of neurodegenerative conditions.

Wang et al. show the recruitment of the lipid channel protein VPS13C and formation of VPS13C-dependent contacts between endoplasmic reticulum and lysosomes after lysosomal damage.

The LPD-3 complex structure reveals protein–lipid interactions that suggest a model for how the native LPD-3 complex mediates bulk lipid transport and provides a foundation for mechanistic studies of bridge-like lipid-transport proteins.

Martín-Arana et al. present a highly sensitive tumor-agnostic assay to detect minimal residual disease based on whole-exome sequencing of longitudinal circulating tumor DNA samples from persons with relapsed colon cancer and on genomic data from metastases.

Dynamic cytoskeletal regulation of lymphatic endothelial cell shape, induced by isotropic stretch and crucial for dermal lymphatic capillary function, is identified and found to result from continuous remodelling of cellular overlaps that maintain vessel integrity.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Organometallic perovskite solar cells exhibit good efficiency but their photostability is still relatively poorly understood and controlled. Here the authors show that photo-degradation arises from the formation of light-activated meta-stable trap states, is reversible, and can be frozen at 0 °C.

X-linked adrenoleukodystophy (X-ALD) is a highly variable, progressive neurodegenerative disorder. In this study, neurofilament light chain protein (NfL) was identified as a potential early distinguishing biomarker.

Determining uterine receptivity before embryo transfers is a major barrier in IVF. Here they identify a FOXA2-dependent preimplantation differentiation process in uterine glands that yields expanded branching, and which could be a useful measure of uterine receptivity.

The functions of small nucleolar RNAs (snoRNAs) in cancer remain to be studied. Here the authors show that the snoRNA Snord67 promotes lymph node metastasis of breast cancer cells through guiding modifications of the spliceosome and regulating the splicing landscape.

Innate IL-17-producing T cells—in particular, adipose γδ17 T cells—are enriched in molecular-clock genes, and the circadian expression of IL-17A and RORγt by these cells has a role in maintaining local homeostasis and regulating lipogenesis.

In this work, researchers engineer HIV-1 immunogens using molecular dynamics simulations to enhance vaccine designs that select for specific antibody mutations. Their approach improved the selection of mutations crucial for broadly neutralizing antibody responses, offering a promising strategy for HIV vaccine development.

Computational drug discovery is used to identify a 12-mer peptide derived from BRINP2 with potent anti-obesity effects that are independent of leptin, glucagon-like peptide 1 receptor and melanocortin 4 receptor.

Conducting a simulated turtlegrass herbivory experiment across 650 experimental plots and 13 seagrass meadows, the authors show that the negative effects of herbivory increase with latitude, driven by low levels of light insolation at high latitudes.

Mice possess neurons in the preoptic area of the hypothalamus that are sensitive to violet light; these deep brain neurons sense light via OPN5 and regulate adaptive thermogenesis in brown fat.