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Graham and colleagues analyzed locally advanced esophageal adenocarcinoma clinical trial patient samples and identified major changes in gene expression profiles and immune microenvironment composition independent of changes in clonal composition.

The role of glioma cellular metabolism in response to oncolytic herpes virus (oHSV) therapy remains to be studied. Here the authors report that oHSV induces metabolic reprogramming in IDH wildtype glioma cells, leading to ferroptosis and anti-tumor immune response. Pharmacological blockade of mutant IDH enhances glioma cell sensitivity to oHSV therapy.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

We show the evolution of a case of EGFR mutant lung cancer treated with a combination of erlotinib, osimertinib, radiotherapy and a personalized neopeptide vaccine targeting somatic mutations, including EGFR exon 19 deletion.

A human SARS-CoV-2 challenge study in individuals without previous exposure to the virus or vaccines provides detailed profiles of local and systemic epithelial and immune cell response dynamics over time and infection status.

A millihertz frequency X-ray quasi-periodic oscillation has been observed near the innermost orbit of an actively accreting supermassive black hole and its frequency has evolved significantly over 2 years, a phenomenon that is difficult to explain with existing models.

Polynitrogen compounds are of interest on a fundamental level and as potential high-energy-density materials. A crystalline solid that consists of two isomeric forms of N₈ molecules held together by weak van der Waals interactions has now been predicted to exist, and to be stable even at low pressures.

Despite the impressive demonstrations with silicon and oxide memristors, realizing efficient roots of trust for resource-constrained hardware remains a challenge. Here, the authors exploit switching behavior in one dimensional perovskite memristors to design security primitives for key generation and device authentication.

Dutta et al. show that impaired mitochondrial fatty acid synthesis (mtFAS) leads to neurodegeneration, increased ceramide levels and disturbed iron metabolism in flies and in fibroblasts from individuals with a mutation in an mtFAS enzyme.

Gandhi, Zivkovic, Østergaard and colleagues describe a bispecific antibody, HMB-001, which could be used for the prophylactic treatment of patients with genetic bleeding disorders, currently treated acutely with recombinant coagulation factor VIIa. HMB-001 can bind and accumulate endogenous FVIIa and localize it to sites of vascular injury by targeting it to the TREM-like transcript-1 receptor selectively expressed on activated platelets.

In an interim analysis of a phase 1/2 trial, a heterologous prime boost vaccine comprised of a chimpanzee adenovirus and self-amplifying mRNA that encodes neoantigens derived from common oncogenic driver mutations in combination with immune checkpoint blockade was safe and elicited neoantigen-specific T cell responses in patients with advanced solid tumors.

Vyas et al. show that epicardial adipose tissue is a reservoir for a subpopulation of tissue-resident memory T cells that can increase the vulnerability of the heart to atrial fibrillation.

Mitochondrial Ndufs4, a subunit of complex I, is a regulator of the electron transport chain. Here, the authors show that forced expression of Ndufs4 in podocytes improves the assembly of respiratory supercomplexes, maintains cristae integrity, and mitigates the progression of diabetic kidney disease

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

The antidepressant vortioxetine affects rodent and human 5-HT₃ receptors differently. López-Sánchez et al. use a variety of methods, including structure determination of vortioxetine-bound human and mouse 5-HT₃ receptors, to reveal the basis of these differences.

Peng et al. find that immunodominant cytotoxic T lymphocytes (CTLs) specific for NP_105–113-B*07:02 are associated with reduced COVID-19 severity. Mechanistically, NP_105–113-B*07:02-specific CTLs show potent antiviral functionality and may represent rational T cell vaccine targets.

One approach to altering the properties of π-conjugated oligomers is conformational engineering, in which the degree of rotation around the bonds linking monomers is restricted. Here the authors apply the conformational engineering approach on individual monomers using tethers of varying lengths to twist the aromatic units, and study the effects of varying the angles.

Molecular details of how antidepressant drugs bind to the human serotonin transporter are not currently clear. Here, the authors introduce photo-cross-linkers into the protein and map the binding site of several antidepressants.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Images and spectroscopy obtained by the JWST from two HSC-SSP quasars show massive, compact and disc-like galaxies, indicating that the relation between black holes and their host galaxies was in place less than a billion years after the Big Bang.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

Existing clinical models cannot fully capture smoldering multiple myeloma (SMM) heterogeneity. Here, integration of 42 genetic alterations from 214 SMM patients using an unsupervised binary matrix factorization clustering approach results in the identification of 6 distinct molecular and clinical subtypes.

The serotonin transporter (SERT) terminates serotonin signaling and its activity is modulated by antidepressants. Here authors reveal the mechanistic details underlying the coupling between the two binding sites in SERT and a high-affinity ligand for the allosteric site.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

The fabrication of synthetic nanochannels for ion separation is challenging. Here, the authors synthesize angstrom-scale ion channels featuring one-dimensional to three-dimensional pore configurations by growing metal‒organic frameworks into nanochannels; the structure of the pore influences the ion transport performance.

Donnan electrical potential is widely adopted to describe ion distribution between two solutions separated by a permeable membrane with implications for many chemical and biological systems. Aydogan Gokturk et al. directly measures this potential for the first time and compare the data with theoretical models.

Patient notes contain shorthand and abbreviations that may be jargon or clinical vernacular. Here the authors train large machine learning models on public web data to decode such text by replacing abbreviations with their meanings.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

A comparison of T cell receptor repertoire profiling methods shows substantial differences in their outputs.

Arp2/3 is a seven-subunit actin-nucleating complex. Here, Chorev et al.identify a novel ‘hybrid complex’ consisting of the actin-nucleating three-subunit core of Arp2/3 and the focal adhesion adapter, vinculin, that localizes to, and modulates the growth of, focal adhesions.

PolyQ-Htt inhibits fast axonal transport in cellular and animal Huntington's disease models. Here, the authors show that this effect is a result of the activation of JNK3. PolyQ-Htt–activated JNK3 reduces kinesin-1 binding to microtubules.

RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

Podocyte injury is central to kidney dysfunction in diabetic nephropathy. Here the authors show that Msk2 is a target of miR-93 and this interaction mediates pathogenic chromatin remodelling in diabetic nephropathy.