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Antibodies stimulating the T cell co-activator 4-1BB (CD137) do enhance anti-tumour T cell function, but their utility is hampered by on target, off tumor toxicity. Here authors show that anchoring anti-4-1BB to tumours via fusion with the collagen binding protein LAIR diminishes systemic dissemination of the drug, and they demonstrate a curative effect in a triple-combination-therapy that relieves regulatory T cell immunosuppression in a mouse model of cancer.

Several genomic features have been found for acute myeloid leukaemia (AML) but targeted clinical genetic testing fails to predict prognosis. Here, the authors generate an AML prognostic score from RNA-seq data of patients, which successfully stratifies AML patients and which may provide guidance for therapeutic strategies.

CXCR2 antagonism has been shown to be anti-arthritic, but anti-chemokine therapies usually fail in the clinic owing to redundancy in chemokine-receptor interactions. Here the authors develop single-chain antibodies with multiple chemokine specificities to achieve high affinity and broad specificity to mouse and human CXC chemokines with efficacy in a K/BxN serum transfer model of arthritis.

Recovery of skilled motor function in rodents after stroke correlates with the restoration of low-frequency quasi-oscillatory activity in the motor cortex, and neuromodulatory electrical stimulation targeting this activity can further accelerate recovery.

Cryptosporidium parvum virus 1 is a virus harbored by the pathogenic protozoan Cryptosporidium parvum, and whose role in parasite biology and host interactions remains unclear. Here, Deng et al. demonstrate the impact this virus has on host response and infection outcome.

Using a neural network trained on bacterial growth inhibition data, in silico prediction of molecules with activity against Acinetobacter baumannii led to the identification of the narrow-spectrum abaucin, which perturbs lipoprotein trafficking.

Nascent transcription in genes and enhancers genome-wide at the single-cell level is quantified using global run-on and sequencing (GRO–seq) with click chemistry.

Gaglia et al. show, using single-cell imaging and analysis in human tumours, that phase transition of heat-shock factor 1 (HSF1) to form intranuclear stress bodies mediates cell-fate decisions underlying cell survival or death.

Prime editing sensor libraries evaluate diverse genetic variants in their endogenous genomic contexts.

Despite major drug discovery efforts, the therapeutic options for glioblastoma (GBM) remain inadequate. Here they analyze patient-derived xenograft model of GBM to quantitatively map distribution and cellular response to the EGFR inhibitor erlotinib, and report heterogeneous erlotinib delivery to intracranial tumors to be inadequate to inhibit EGFR signaling.

The local delivery of a calcium channel blocker and a Rho-kinase inhibitor, determined by screening for small molecules that cause ureteral relaxation, significantly reduce ureteral contraction in pigs.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

The delivery route and dose of the BCG vaccine profoundly alters the protective outcome after Mycobacterium tuberculosis challenge in non-human primates.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

Voxel-based morphometry (VBM) involves comparisons of high resolution structural images of the brain between groups, but what causes changes in the VBM signal is unclear. Here the authors perform a VBM study of Thy1-YFP mice following auditory fear conditioning and propose that the signal changes can be partially explained by increases in dendritic spine density.

Automated fabrication of microneedle patch mRNA vaccines for COVID-19 may improve vaccine access.

Machine learning has now been shown to enable the de novo design of abiotic nuclear-targeting miniproteins. To achieve this, high-throughput experimentation was combined with a directed evolution-inspired deep-learning approach in which the molecular structures of natural and unnatural residues are represented as topological fingerprints. The designed miniproteins, called Mach proteins, are non-toxic and can efficiently deliver antisense cargo in mice.

Systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA for silencing genes in bone-marrow endothelial cells of mice improved the healing of the mice after myocardial infarction.

Fukazawa et al. report that SIV persists in follicular helper T cells in elite controller macaques, evading clearance by CD8+ T cells

Prime-editing mouse models enable the study of specific cancer mutations in vivo.

Large-scale Mendelian randomization and colocalization analyses using gene expression and soluble protein data for 1,263 actionable druggable genes, which encode protein targets for approved drugs or drugs in clinical development, identify IFNAR2 and ACE2 as the most promising therapeutic targets for early management of COVID-19.

Self-assembly of small drugs with organic dyes represents a facile route to synthesize nanoparticles with high drug-loading capability. Here the authors combine a machine learning approach with high-throughput experimental validation to identify which combinations of drugs and excipient lead to successful nanoparticle formation and characterize the therapeutic efficacy of two of them in vitro and in animal models.

RAPTR, a lentivirus surface display-based library-on-library screening method to decipher antigen and immunoreceptor identities

Synthetic promoters can be superior to native ones but the design is challenging without knowledge of gene regulation. Here the authors develop a pipeline that allows for screening a synthetic promoter library to identify high performance promoters in potentially any given cell state of interest.

Engineered biosensing bacteria can potentially probe the human gut microbiome to prevent, diagnose, or treat disease. Here the authors present a robust biocontainment assisted by Cas9 and an engineered gene expression control combined in a genetically engineered human commensal bacterium that successfully functioned in a mouse intestinal tract as well as cell culture condition.

Vicinity of small bodies might be dangerous to the spacecrafts and to their instrumentation. Here the authors show the operational environment of asteroid Bennu, validate its photometric phase function and demonstrate the accelerating rotational rate due to YORP effect using the data acquired during the approach phase of OSIRIS-REx mission.

Here, the authors describe the global distribution of crAssphage, its presence in Old-World and New-World primates, and its association with gut bacterial communities and dietary factors, providing insights into the origin, evolution and epidemiology of human gut crAssphage.

Rationally designed polymer vesicles increase cytosolic delivery of cGAMP, activating the STING pathway and increasing the immunogenicity of the tumour microenvironment in in vivo murine models of melanoma and in human metastatic melanoma tissues.

Theory predicts that organisms in varied environments should evolve to be more phenotypically flexible. Evidence combining genetic and physiological variation with thermal acclimation experiments shows that the thermogenic flexibility of wild juncos is greatest in populations where temperatures are most variable.

The intratumoural injection of recombinantly expressed cytokines bound tightly to the common vaccine adjuvant aluminium hydroxide leads to weeks-long retention of the cytokines in the tumours with minimal side effects, as shown in multiple syngeneic mouse models.

Bennu’s surface has experienced continuous changes, mostly induced by its accelerating spin rate, which could have resulted in a collapse of its interior in the past. This scenario is also supported by the heterogeneity of Bennu’s internal mass distribution.

Bennu’s surface presents evidence of a variety of particle sizes, from fine regolith to metre-sized boulders. Its moderate thermal inertia suggests that the boulders are very porous or blanketed by thin dust. Bennu’s boulders exhibit high albedo variations, indicating different origins and/or ages.

GATA-binding protein 4 (GATA4) is reported to control cell proliferation in cancers. Here the authors show that GATA4’s pro-inflammatory secretome promotes the recruitment of immune cells such as CD8 + T cells to suppress tumour initiation and growth in a non-cell autonomous manner.

The analysis of longitudinal bulk and single-cell multi-omics data is a highly complex task. Here, the authors introduce PALMO, a software platform with five modules to analyse longitudinal bulk and single-cell multi-omics data, which is extensively tested in external datasets that include multiple omics modalities.

A druggable genome CRISPR-Cas9 screen followed by functional validation in preclinical lung cancer models uncovers Slc33a1 as a Keap1-mutant-specific targetable dependency.

Signatures of phyllosilicate-like hydrated minerals are widespread on Bennu’s surface, indicating significant aqueous alteration. The lack of spatial variations in the spectra down to the scale of ~100 m indicates both a relatively uniform particle size distribution and a lack of compositional segregation, possibly due to surficial redistribution processes.

Zika virus infection during pregnancy can result in birth defects, but underlying pathogenesis at the maternal-fetal interface is unclear. Here, the authors use non-invasive in vivo imaging of Zika-infected rhesus macaques and show that infection results in abnormal oxygen transport across the placenta.

Sensors of the NLR family generally activate innate immunity. Ting et al., however, demonstrate that the little-known NLRC3 negatively regulates Toll-like receptor signaling by altering ubiquitination of the signaling adaptor TRAF6.

Combined analysis of proton-proton collision data from the Large Hadron Collider at CERN by the CMS and LHCb collaborations leads to the observation of the extremely rare decay of the strange B meson into muons; the result is compatible with the standard model of particle physics, and does not show any signs of new physics, such as supersymmetry.

Near-Earth rubble-pile asteroid Bennu has an unexpectedly old surface, with numerous candidate impact craters and morphologically diverse boulders, according to early observations by the OSIRIS-REx mission.

Cardiomyocyte transplantation after heart attack improves contractile function in monkeys.