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Chimeric antigen receptors (CAR) are a promising option for cell-based immunotherapy for cancer and other immune diseases. Here the authors develop speedingCARs, an integrated CAR design and screening platform based on modular signaling ___domain shuffling and single cell transcriptomic analyses, and test its potential for identifying and validating novel CAR designs.

CAR T cell therapy shows promise for achieving long-term drug-free remission in various autoimmune diseases. This Review discusses the ongoing challenges and unanswered questions of CAR T cell therapy in autoimmune diseases, including pre-procedural, procedural and post-procedural considerations.

MacDonald et al. show that EGF triggers de-sialylation of plasma membrane glycoproteins like integrins in a mechanism that depends on the Na⁺/H⁺ antiporter NHE1 and the neuraminidases Neu1 and Neu3. Integrins are trafficked to the Golgi and re-sialylated.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Resolving the kinetics of energy dissipation during photosynthesis is challenging due to complex photophysics and the coexistence of multiple antenna proteins. Here Son et al. overcome this by applying ultrabroadband 2D spectroscopy to LHCII reconstituted in lipid nanodiscs, revealing mechanisms of dissipation enhanced by the membrane.

Using the game Gran Turismo, an agent was trained with a combination of deep reinforcement learning algorithms and specialized training scenarios, demonstrating success against championship-level human racers.

In plants, photoprotective non-photochemical quenching involves CP29 proteins. Their conformational change induced by acidification of the thylakoid lumen brings three chlorophylls together, activating a channel to dissipate excess energy as heat.

This analysis shows that demand-side policies can reduce emissions by 51–85% in buildings and 37–91% in transport by 2050, with electrification having the greatest impact. Adopting a mix of strategies offers benefits for the overall energy system.

Population differences in immune responses to SARS-CoV-2 can be explained by environmental exposures, but also by local adaptation acting through genetic variants acquired after admixture with archaic hominin forms.

Small-molecule responsive protein switches are crucial components to control synthetic cellular activities. Here, we present a computational protein design strategy to repurpose drug-inhibited protein-protein interactions into OFF- and ON-switches active in cells.

The antitumour activity of bispecific antibodies in immunocompromised hosts can be potentiated via allogeneic T cells engineered with a T-cell receptor that decouples antigen-mediated T-cell activation from T-cell cytotoxicity.

The use of time-bin entangled qudits is hindered by the phase instability, timing inaccuracy and low scalability of current interferometric schemes. Here, the authors show a fiber-pigtailed photonic chip for generating and processing picosecond-spaced time-bin entangled qudits and utilize the system to implement a quantum key distribution protocol.

ALK genetic alterations drive various malignancies through aberrant tyrosine kinase activation, promoting oncogenic cell growth and survival. Here, Voena et al. outline recent advances in ALK oncogenic signalling, mechanisms of resistance, and both existing and promising new modalities to treat ALK-driven tumours.

West Nile virus is an animal pathogen that has spread rapidly in Europe in recent years, causing several human deaths. This study investigates the spatial and temporal dynamics of the virus circulation between Africa (its place of origin) and Europe.

On-chip nonlinear optics devices find a number of applications in modern optics from spectroscopy to communications. Here, the authors increase the degrees of freedom for frequency mixing by demonstrating the nonlinear interaction of perpendicularly-polarized modes in an integrated microring resonator.

A comparison of RNA-seq and microarray data from samples treated with diverse drugs highlights a dependency of cross-platform concordance on treatment effect.

A DNA-encoded chemical library based on regio- and stereoisomers of phenylalanine has been synthesized and used for affinity-based selections against multiple target proteins. This approach led to the isolation and validation of potent ligands capable of CAR T-cell activation and tumour targeting.

Plants protect their photosynthetic apparatus from excess light energy through non-photochemical quenching (NPQ). This study shows that NPQ is catalysed by two independent mechanisms, only one of which is dependent on lutein.

Cell engineering by synthetic biology typically relies on synthetic gene constructs that compete with the host cell for intracellular resources. This Review discusses how such resource competition can impact mammalian cell engineering and outlines strategies for how to mitigate cellular burden using circuit-centric and host-centric approaches.

Spectroscopy from the JWST Advanced Deep Extragalactic Survey of a galaxy at redshift 13 shows a singular, bright emission line identified as Lyman-α, suggesting the onset of reionization only 330 Myr after the Big Bang.

The chemical sector is both hard-to-abate and hard-to-defossilize. This study shows how limiting the availability of alternative carbon feedstocks impacts climate goals and efforts to phase out fossil fuels.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Microscopic understanding of the electrical double layer (EDL) is key to optimizing interfacial processes in water splitting and batteries. Here, the authors report the insight of EDL at oxide-electrolyte interfaces with ab initio machine learning simulations that agrees with available experiments.

A quadruple mutant of Arabidopsis lacking all four subunits of light harvesting complex I (LHCI) compensates by binding LHCII complexes to photosystem I instead. This maintained similar excitation energy transfer efficiency but with a much reduced absorption cross-section.

SimiC, a single-cell gene regulatory inference framework is presented that can infer multiple gene regulatory networks across related cell phenotypes, unraveling complex regulatory dynamics.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Here, the authors discover small molecules that inhibit glycosylation processes that occur in the Golgi apparatus of cells. The molecules reversibly inhibit formation of elaborate glycan structures without affecting secretion of glycoproteins.

In this Review, Harris et al. summarize the dynamic changes of the immune breast tumour microenvironment (TME) that take place during disease progression and in response to treatment, and outline emerging therapies to target the immune TME in patients with breast cancer.

Surgical resection is the primary treatment strategy for glioblastoma multiforme, but the infiltrating nature of the tumour, coupled with its heterogeneity and the presence of the blood–brain barrier that hampers drug delivery, contributes to recurrence and poor prognosis. Here the authors engineer a mechanically flexible mesh that can adhere to the tumour resected cavity and release a combination of nanomedicines and small molecules in a controlled and sustained manner for tumour therapy.

The latent human immunodeficiency virus (HIV) reservoir in patients poses a problem for HIV cure. Here, Li et al. show that a combination of compounds inducing viral reactivation and cell death, inhibiting autophagy and blocking new infections can eliminate HIV infection in 50% of humanized HIV infected mice and in blood samples from infected patients.

The natural antisense transcript MAPT-AS1 interferes with translation of mRNA transcript into tau protein in the brain and may represent a general mechanism for controlling levels of intrinsically disordered proteins, with particular relevance for neurodegeneration.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Even though the Grotthuss mechanism was proposed two centuries ago, it is still unclear why proton transfer via the hydroxide ion is slower than that via hydronium. Advanced ab initio molecular dynamics simulations now show that it is because proton transfer via hydroxide is less temporally correlated than transfer via hydronium.

As corals struggle to survive under climate change, it is crucial to know whether they can withstand increasing seawater temperatures. Using a controlled thermal stress experiment across three divergent coral holobionts, this study examines metatranscriptomic responses to heat stress corresponding to the coral host, photosymbionts and associated microbiota.