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Forced expression of C-X-C chemokine receptor type 6 in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer.

An economic evaluation can provide insights into the cost-effectiveness of different kidney replacement therapy modalities to inform decisions on how to best allocate limited resources. This evidence-based Guideline is aimed at equipping policymakers and medical personnel with insight into the principles of economic evaluation within the context of policies for kidney-failure services, and increasing their confidence in requesting and using economic evidence derived from such evaluations.

In a phase-I/II trial in healthy adults, the BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells against SARS-CoV-2 epitopes that are conserved in a wide range of currently circulating variants.

The lysosomal polyamine transporter ATP13A2 controls the cellular polyamine content, and impaired lysosomal polyamine export represents a lysosome-dependent cell death pathway that may be implicated in ATP13A2-associated neurodegeneration.

Mitochondrial complex I deficiency is frequent in congenital, neurologic and cardiovascular disease. Here the authors demonstrate that Complex I stimulates the turnover of a mitochondrial calcium channel, which becomes stabilized during Complex I deficiency, preserving energetic homeostasis.

Here, the authors introduce a computational strategy for antimicrobial discovery that addresses the scarcity of large datasets. Based on data-driven representations of molecular structures, this framework uncovers new growth inhibitors of Staphylococcus aureus.

This work reveals the diversity and extent of human antibody specificities in Chagas disease and provides a wealth of well-defined antigenic markers for diagnosis and development of serological applications for this neglected infectious disease.

We demonstrate that the transmembrane protease TMPRSS2 is a receptor for coronavirus HKU1; it triggers HKU1-mediated cell–cell fusion and viral entry by binding to both HKU1A and HKU1B spikes.

Differential sensing aims to mimic senses such as taste and smell through the use of synthetic receptors. Here, the authors show that arrays of de novo designed peptide assemblies can be used as sensor components to distinguish various analytes and complex mixtures.

An artificial intelligence model defines a data-driven set of total parenteral nutrition compositions to assist clinicians in personalized treatment of neonates in intensive care and is able to adapt recommendations to patient status, with validation from large external cohorts and a blinded reader study.

The bispecific IgG1-like CoV-X2 prevents SARS-CoV-2 spike binding to ACE2, neutralizes SARS-CoV-2 and its variants of concern, protects against disease in a mouse model, whereas the parental monoclonal antibodies generate viral escape.

The enzyme LspA from the human pathogen Staphylococcus aureus (MRSA) contributes to the integrity and function of the bacterial cell envelope. Here, authors provide crystal structures of LspA in complex with two natural antibiotics, which have profoundly different structures but inhibit LspA in an identical way.

This study reveals that E. coli lipoate-protein ligase A (LplA) exhibits reversible phase separation and forms condensates in cells, which can be specifically regulated by small molecules, offering chemical tools for synthetic biology and biomedicine.

Plant pathogens translocate type III effector (T3E) proteins that may be recognized by plants to trigger immunity. Here, the authors show that the Xanthomonas T3E XopH possesses a novel 1-phytase activity that is required for XopH-mediated immunity of plants carrying the Bs7 resistance gene.

The authors highlight inconsistencies and divergencies in the literature reporting data on indirect calorimetry for studies on whole-body energy homeostasis, and propose harmonization of standards to facilitate data comparison and interpretation across different datasets.

This linear ANOVA-based method quantifies the activity of different combinations of genetic elements and assigns a score that indicates the variation in performance across changing contexts.

Transitioning from spores to hyphae is crucial for host invasion by the plant pathogenic fungus Zymoseptoria tritici. Here, the authors show that the spore-to-hypha transition is enhanced by wheat leaf surface compounds and is regulated by the white-collar complex, which integrates light with biotic and abiotic cues to allow host invasion through open stomata.

Dysregulation of protein degradation by the ubiquitin-proteasome system is a feature commonly associated with cancer. Here, the authors develop an orally available small molecule that inhibits CSN5, the proteolytic subunit of the COP9 signalosome, and blocks tumour growth in a xenograft model.

This protocol describes how to prepare membrane-bound, complex protocells with life-like capabilities by using building blocks from two distinct bacterial colonies spatially segregated within individual coacervate microdroplets.

Steroid units can facilitate membrane permeation and bioavailability in drugs. Here, using a medicinal chemistry program, Krieget al. identify an arylmethylamino steroid that kills Plasmodium parasites, likely through a chelate-based quinone methide mechanism, and has activity against Schistosoma mansoni.

Cryogenic electron microscopy structures of the Synechocystis phycobilisome—alone and bound with orange carotenoid protein—reveal detailed information regarding the biophysical basis of the control of cyanobacterial light harvesting.

ARGONAUTE (AGO) is the core protein component of small RNA-guided silencing complexes. Free, but not RNA-bound, AGO turns over rapidly. The authors identify a structural AGO switch whose accessibility only in the free state confers rapid degradation.

Lysophosphatidic acid is known to increase in concentration in multiple cancer types. Here, the authors show it affects CD8 T cell metabolism, phenotype, and effector functions, and plasma concentrations appear predictive of response to immunotherapy.

The transfer of electronic energy through a photosystem can harm the photosynthetic apparatus when not balanced with CO₂ fixation. Here, the authors show that CO₂ modulates electronic energy transfer in cyanobacteria by binding to and enhancing the activity of the light-harvesting complex.

mTORC1 blocks lysosomal nutrient generation. Here, the authors show that mTORC1 inactivation triggers V-ATPase assembly, which rapidly initiates lysosomal acidification and degradation of protein contents throughout the lysosomal population.

Intravascularly infused extracellular matrix from ventricular myocardium binds to leaky vasculature and induces the regeneration of inflamed heart tissue, as shown in rats and pigs.

Rational design was used to develop a suite of red-shifted, bioconjugatable heptamethine cyanine dyes for multiplexed in vivo imaging in the shortwave-infrared/near-infrared-II region.

Zorya uses a membrane-anchored H⁺-driven rotary motor ZorAB to sense phage invasion and to recruit the intracellular effectors ZorC and ZorD that execute anti-phage defence.

Kinases are a widely targeted enzyme class in cancer chemotherapy. Several clinically used kinase inhibitors also inhibit bromodomains, epigenetic ‘readers’ of acetylated lysine residues, suggesting that kinase-bromodomain polypharmacology may offer benefits in therapeutic settings.

Together with the fatty-acid-binding protein  FABP5, the cytoskeletal organizer TAGLN2 is an essential factor for fatty acid uptake, mitochondrial respiration and anticancer function in CD8⁺ T cells.

The heterogeneity of androgen receptor (AR) gene alterations across metastases in prostate cancer remains unresolved. Here, the authors characterise AR genomic complexity across spatially separated lethal metastases from 10 prostate cancer patients and investigate how AR alterations evolve.

Combined methylmalonic acidemia (MMA) and hyperhomocysteinemias are inborn errors of vitamin B12 metabolism, and mutations in the transcriptional regulators HCFC1 and RONIN (THAP11) underlie some forms of these disorders. Here the authors generated mouse models of a human syndrome due to mutations in RONIN (THAP11) and HCFC1, and show that this syndrome is both an inborn error of vitamin B12 metabolism and displays some features of ribosomopathy.

Here, the authors isolated and characterized genetic features of spike-specific monoclonal antibodies. They show how the antibodies evolve from infection to after vaccination and conclude that highly polyclonal repertoires of affinity-matured memory B cells are efficiently recalled by vaccination.

Here the authors propose an RNA interference-based switch for dynamic control of AAV transgene expression. In this approach, transgene expression may be silenced by RNAi and subsequently recovered using REVERSIR oligonucleotides.

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a powerful tool for neuroscience, but the standard DREADD ligand, CNO, has significant drawbacks. Here the authors report two novel high-potency DREADD ligands and a novel DREADD radiotracer for imaging purposes.

A dust impact event detected by the ROSINA mass spectrometer towards the end of the Rosetta mission brings evidence of the presence of ammonium salts in comets. Ammonium salts can store enough nitrogen to explain the observed nitrogen depletion in comets and may have a role in amino acid formation.

The biosynthesis of benzylisoquinoline alkaloids such as morphine requires tyrosine oxidases, which are prone to overoxidation. A colorimetric readout that co-opts betaxanthin enzymes now enables discovery of an improved oxidase that, with other enzymes, makes reticuline in yeast.

Here the authors identify PCNA, a master regulator of DNA replication, as a ubiquitin substrate for the BRCA1/BARD1 heterodimer. This modification is crucial to avoid the appearance of unreplicated DNA gaps in the genome after replication.

Under stressful conditions, mesenchymal stromal cells transfer mitochondria to endothelial cells through tunnelling nanotubes, and artificially transplanting mitochondria into endothelial cells improves the ability of these cells to engraft and to revascularize ischaemic tissues.

Mitochondrial Ca2+ homeostasis is reported to influence cellular senescence. Here the authors show that TRPC3 limits senescence by inhibiting IP3R-mediated Ca2+ release and ER mitochondria Ca2+ transfer and that the downregulation of TRPC3 in stromal cells affects SASP production and tumour progression.

Vaccines that interrupt malaria transmission will be important tools for malaria elimination. Here the authors identify a human monoclonal antibody from Pfs230 vaccinated individuals that blocks transmission of Plasmodium falciparum to mosquitoes in a complement-dependent manner and reacts with gamete surface.

Xia et al. show that the activity of the small GTPase RalA is increased in white adipocytes in diet-induced obese mice. RalA enhances mitochondrial fission and therefore reduces energy expenditure, which contributes to weight gain.

Inflammation of brain endothelial cells is seen in neurodegenerative conditions and in aging. Here the authors examine the role of astrocytes in blood brain barrier function using an iPSC-derived cell co-culture model.

Current applications of CD40-directed cancer immunotherapy rely on the release of endogenous tumor antigen for T cell priming and activation. Here the authors develop a bispecific CD40 agonistic antibody for modular delivery of antigenic peptides combined with CD40 stimulation and find that this improves T cell expansion and anti-tumor response in mice.’

Dewald et al. show a high Spike-IgG seroprevalence (95%) in a multicenter study with 1,411 participants. They determined a substantially reduced serum neutralization against the SARS-CoV-2 VOCs BA.4/5 and BQ.1.1. and explored predictive factors of neutralizing activity.

The nasal commensal bacterium Staphylococcus lugdunensis produces a novel cyclic peptide antibiotic, lugdunin, that inhibits colonization by S. aureus in animal models and is associated with a significantly reduced S. aureus carriage rate in humans, suggesting that human commensal bacteria could be a valuable resource for the discovery of new antibiotics.

Meshworks of claudin polymers control the paracellular transport and barrier properties of epithelial tight junctions. Here, the authors show different claudin nanoscale organization principles, finding that claudin segregation enables barrier formation and paracellular ion flux across tight junctions.

A bifunctional AURORA-A degrader induces the fast and specific degradation of this kinase in cancer cell lines, which enables targeting of non-catalytic, oncogenic functions of AURORA-A resulting in S-phase arrest and rampant apoptosis.

UVRAG is involved in autophagy, which loses its tumour suppressor functions when in its truncated form in cancers. Here, the authors use a mouse model that inducibly express this truncated protein and show impaired autophagy, enhanced inflammation and β-catenin stabilisation, which promotes spontaneous tumorigenesis.