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Mesenchymal stem cells (MSC) are used for immunosuppressive therapy and a uniform source or heterogeneity characterisation is needed. Here the authors use multi-omics to compare human MSC from different sources and ages of donors and show differences in gene expression and immunosuppressive function.

This study shows that excitatory neurons in the ventral hippocampus that express the serotonin receptor 2c gene control attention through direct innervation of the mouse equivalent of the Edinger–Westphal nucleus.

Guo et al. show that synaptic alterations in ACC pyramidal neurons underlie social impairments in Shank3 mutant mice and that selective activation of ACC pyramidal neurons or enhancing AMPAR function improves social behavior in these mice.

IDO1-mediated tryptophan metabolism plays an important role in creating an immunosuppressive tumour microenvironment. Here, the authors show that deubiquitinase USP14 regulates immune suppression by inducing IDO1 stabilization and suggest USP14 as a potential therapeutic target to improve immunotherapy in colorectal cancer.

In two cohorts of patients with glioblastoma who received anti-PD-1, Sonabend and colleagues show that ERK1/2 phosphorylation, detected by immunohistochemistry, provides a biomarker for MAPK/ERK pathway activity and better survival on this therapy.

Basal cell carcinoma is a common skin lesion and the risk loci for this cancer are beginning to be understood. In this study, the authors conduct a two-stage genome-wide association study and confirm known risk loci and identify an additional 14 loci.

The molecular mechanisms underlying relapse in pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients remain to be explored. Here, the authors characterise the chromatin accessibility landscape of B-ALL and identify subtype and drug response specific patterns.

A murine colorectal cancer (CRC) model shows that mutant KRAS-STAT4-mediated upregulation of Y chromosome KDM5D contributes to the sex differences in KRAS-mutant CRC, providing an actionable therapeutic strategy for metastasis risk reduction for men afflicted with KRAS-mutant CRC.

O-glycosylation of neuropilin-1 is involved in cancer migration and invasion. Here, the authors show that defects in N-glycosylation of two neuropilin-1 splice variants enhance the co-internalisation of Met, it’s interaction with β1-integrin, and subsequent constitutive activation of FAK/p130Cas signalling in endosomes to promote colorectal cancer metastasis.

Liu and colleagues show that a previously described G396R variant of the human IGHG1 gene offers increased protection from SARS-CoV-2 and bacterial infections.

The three germ layers are formed from the inner cell mass of the mammalian embryo during gastrulation. Here, the authors present a method by which a single mouse embryonic stem cell, derived from inner cell mass, differentiates into the three germ layers in a self-organized manner when cultured in soft fibrin gel.

MAVS is an essential component of the pathogen-sensing machinery, and functions by forming prion-like filaments. Here the authors show that alternatively translated forms of truncated endogenous MAVS can prevent spontaneous aggregation and degradation in cells to sustain MAVS-mediated immune signalling.

Activated Notch signalling promotes cancer metastasis and stemness. Here the authors show that Notch1 activates transcription of DNA replication factor RCF4 and that RCF4 binds and stabilises Notch1 intracellular domain (NICD1) to promote cancer metastasis.

Wu et al. report that IFNγ induces the phase separation of KAT8 and IRF1 into condensates that promote PD-L1 upregulation. They further identify a peptide that blocks KAT8–IRF1 condensates, reducing PD-L1 levels and increasing antitumor immunity.

EGFR is a well-known oncogene; however, the mechanisms regulating its expression are still unclear. Here, analysing genome-wide chromatin associations, the authors show that in breast cancer cells ZNF516 represses EGFR transcription through the interaction with the CtBP/LSD1/CoREST complex.

Incorporating prior knowledge in deep learning models can overcome the difficulties of supervised learning, including the need for large amounts of annotated data. An approach in this area called deep reasoning networks is applied to the complex task of mapping crystal structures from X-ray diffraction data for multi-element oxide structures, and identified 13 phases from 307 X-ray diffraction patterns in the previously unsolved Bi-Cu-V oxide system.

The discovery of efficient drugs is a main challenge in cancer therapy. Here, the authors report a synthetic retinoid, WYC-209 with anti-tumor and anti-metastatic activity mediated by the retinoic acid receptor signaling pathway.

A Si anode with hierarchical morphology can accommodate large volume changes, demonstrates high Coulombic efficiency and cyclability as well as an areal capacity comparable to that of commercial Li-ion batteries.

The cellular protein RIG-I detects viral RNA and activates another protein, MAVS, which then forms filaments and stimulates an antiviral pathway. Here, the authors identify different regions within MAVS involved in activating transcription factors IRF3 and NF-κB, and in MAVS self-inhibition.

Cutaneous squamous cell carcinoma is the second most common type of skin cancer. In this genome-wide association study, which includes over 7,000 cases, the authors identify 4 new susceptibility loci for this cancer and also provide independent replication of 9 previously reported susceptibility loci.

The skin’s tanning response to sun exposure shows great interindividual variability. Here, Visconti et al. perform a genome-wide association study for ease of skin tanning and identify 20 genetic loci, ten of which had not previously been associated with pigmentation-related traits.

In humans, caspase-5 is an LPS sensor that can induce gasdermin D cleavage and pyroptosis. Here, the authors show that zebrafish caspy2 is a functional homolog as it also senses cytosolic LPS to activate the noncanonical inflammasome and to protect against bacterial infection, but it does so via pyrin death domain interactions.

Cholinergic neurons in the diagonal band of Broca degenerate early in Alzheimer’s disease. Here the authors show that in healthy mice, these cholinergic inputs innervate newborn neurons in the hippocampus, and that loss of this innervation in an Alzheimer’s disease model leads to impairments in spatial memory.

Stimulus category, saliency and value all affect the subjective value estimates that guide our decisions. Here, the authors systematically vary their stimuli along these three dimensions in humans and report category independent encoding of values and saliency in the vmPFC and striatum.

The gene CHD1 is synthetic essential in PTEN-deficient prostate and breast cancers.