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In this study, Kreuzaler et al. perform zonal analysis to study metabolic heterogeneity in breast cancer and identify the metabolic dependency on pantothenic acid (vitamin B5) in areas of the tumor that show high expression levels of the oncogene MYC. Dietary restriction of vitamin B5 reverses several MYC-driven metabolic changes and hampers tumor progression.

Antibiotics to treat carbapenem-resistant Acinetobacter baumannii infection are an urgent need. The cerastecins are potent, bactericidal and efficacious in animal models of infection, and may enable new treatment modalities targeting LOS transport.

Evidence is found for phase-tunable Majorana zero modes in scalable two-dimensional Josephson junctions produced by top-down fabrication.

Relativistic 35 MeV electron bunches with charges of 60 pC are accelerated in a terahertz-wave-driven dielectric waveguide. When the terahertz pulse energy is 0.8 μJ, an accelerating gradient of 2 MeV m⁻¹ and energy gain of 10 keV are achieved.

CCR8 is a promising target in cancer immunotherapy. Here, authors generated mAb1, an antagonist antibody against CCR8 and determined structures of CCR8 in complex with mAb1 or the agonist CCL1, providing insights into CCR8 inhibition and activation.

Multidrug efflux protein pumps are key players in bacterial antimicrobial resistance. Here, the authors show how dynamics of a periplasmic pump component can be targeted for efflux inhibition.

In moiré materials, structural relaxation phenomena can lead to unexpected and novel material properties. Here, the authors characterize an unconventional non-local relaxation process in twisted double trilayer graphene, in which an energy gain in one domain of the moiré lattice is paid for by a relaxation that occurs in the other.

Infrared surface phonon polariton tuning is achieved by photoinjecting free carriers into resonators.

How the necroptosis executioner, MLKL, converts to a killer form has been mysterious. Here, authors show RIPK3-mediated phosphorylation of human MLKL is the cue for pseudokinase domain dimerization before assembly of pro-necroptotic MLKL tetramers.

The potential of all-virtual clinical trials in cardiology is shown by the CHIEF-HF trial, conducted in the midst of the COVID-19 pandemic, which found that an SGLT2 inhibitor can alleviate heart failure symptoms in patients irrespective of ejection fraction or diabetes status.

A monolayer of tungsten oxyselenide, created by oxidizing a layer of tungsten diselenide, can be used to efficiently dope graphene, leading to a room-temperature mobility of 2,000 cm² V^–1 s^–1 at a hole density of 3 × 10¹³ cm^–2.

Bilayer WSe₂ field-effect transistors with near ideal device characteristics can be created using transferred via contacts made from metal-embedded hexagonal boron nitride.

Thermoelectricity due to the interplay of the nonlocal Cooper pair splitting and the elastic co-tunneling in normal metal-superconductor-normal metal structure is predicted. Here, the authors observe the non-local Seebeck effect in a graphene-based Cooper pair splitting device.

The SIGNAL Phase 2 study of pepinemab immunotherapy in early Huntington’s disease (HD) did not meet its coprimary clinical efficacy endpoints, but had a favorable safety profile and showed a significant treatment-related reduction in caudate brain atrophy and reversal of the characteristic decline in brain metabolic activity that is typical of HD progression.

IgE mediates allergic hypersensitivity and it is found tightly associated with its cellular receptor FcɛRI. Now crystal structure and binding studies reveal that the Cɛ2 domain from IgE Fc, which does not contact the receptor, contributes nevertheless to the high affinity by rendering the Cɛ3 domain more ordered, and thus minimizing the entropy gain upon receptor dissociation.

Although immune checkpoint blockade is a standard treatment for patients with malignant mesothelioma, only a minority of patients exhibit radiological response. In a phase II clinical trial (MIST4) investigating the efficacy, safety and molecular correlates of response following treatment with atezolizumab and bevacizumab, the authors demonstrate that the gut microbiota may modulate responsiveness to treatment.

Glycolytic enzymes are challenging drug targets due to their highly conserved active sites and phosphorylated substrates. Here, the authors identify fast acting allosteric inhibitors of Trypanosoma brucei phosphofructokinase that block trypanosome glycolysis and provide cure evidence in murine model.

RNA modifications represent a critical aspect of RNA biology that is not well suited to sequencing methods. Here, the authors provide a software tool for automated analysis of RNA tandem mass spectra with full support of modifications, isotope labelling, and control of false discovery rate.

Protein serial crystallography at X-ray free-electron lasers (XFELs) is a powerful technique for structure determination. Here, authors present a device for sample delivery designed to abate challenges to non-specialists allowing for compound screening.

High-speed atomic force imaging allows for the visualisation of molecular‐level activity in real-time. Here, the authors use HS-AFM to image the activity of an antimicrobial peptide on a membrane and are able to detect previously unknown molecular mechanisms behind its action.

The cyanobacterium Synechococcus elongatus is a model organism for the study of circadian rhythms, and is naturally competent for transformation. Here, Taton et al. identify genes required for natural transformation in this organism, and show that the coincidence of circadian dusk and darkness regulates the competence state in different day lengths.

Plasmodium falciparum moves by an atypical process called gliding motility which comprises of atypical myosin A (PfMyoA) and filaments of the dynamic and divergent PfActin-1 (PfAct1). Here authors present the cryo-EM structure of PfMyoA bound to filamentous PfAct1 stabilized with jasplakinolide and provide insights into the interactions that are required for the parasite to produce the force and motion required for infectivity.

A remarkably low critical current is found to reorient the magnetic order in a magnetically intercalated transition metal dichalcogenide, suggesting this class of materials could form a basis for antiferromagnetic spintronics.

Bacteria and archaea use tripartite ATP-independent periplasmic (TRAP) transporters to import essential nutrients. Davies et al. report a high resolution structure of a TRAP and show that it uses an ‘elevator-with-an operator’ mechanism.

Abrupt changes in atmospheric methane through the last deglaciation were largely the result of tropical sources responding to shifting rainfall patterns, according to a comparison of precisely dated ice cores in Greenland and Antarctica.

High-speed spectroscopy confirms predictions of the emission of terahertz radiation when a laser-induced acoustic wave passes across the interface between two piezoelectric materials.

The ability of T cells to migrate is a central component of their functionality and is known to require WNK1 kinase that is linked to the influx of ions into the cell. Here the authors show that T cell migration requires WNK1 mediated ion and water influx to swell the membrane of the leading edge and support actin polymerisation and forward motility.

An orally bioavailable small-molecule active-site inhibitor of the phosphatases PTPN2 and PTPN1, ABBV-CLS-484, demonstrates immunotherapeutic efficacy in mouse models of cancer resistant to PD-1 blockade.

TRB proteins have been shown to recruit PRC2 for H3K27me3 deposition. This work shows that TRBs also recruit JMJ14 to remove H3K4me3, demonstrating that TRBs silence the target genes via a combinatorial histone modification mechanism.

An mRNA-based therapeutic can drive expression of a functional antibody in humans at levels capable of neutralizing Chikungunya virus ex vivo.

The ensemble of massless electrons in graphene shows a collective non-zero inertia that can be measured by measuring the kinetic inductance of an encapsulated graphene device.

The authors use surface acoustic waves, focused in a Gaussian geometry, to manipulate the spin state of divacancy defects in silicon carbide via mechanical driving. They demonstrate that shear strain is important in controlling the spin transitions.

Here the authors describe a functional screening platform in human stem cells to identify and optimize protein-based gene editing additives that increase homologous directed recombination and have potential to improve gene therapy workflows.

The insertion of metal atoms and heteroaromatic units provides a way to tune the optical, electronic and magnetic properties of graphene nanoribbons. Now the synthesis of a porphyrin-fused graphene nanoribbon with a narrow bandgap and high charge mobility has been achieved, and this material used to fabricate field-effect and single-electron transistors.

Physicochemical heterogeneity poses a significant constraint in photocatalyst advancement. Here the authors introduce a multimodal optical microscopy platform to assess activity and defects concurrently in photoelectrocatalysts, revealing that disorder can unexpectedly enhance local photoelectrocatalytic performance in certain instances.

Step-economical and efficient syntheses of Spongistatin 1 analogs are desirable for the development of potent anti-proliferative agents. Here, the authors report a 22-step synthesis of a D-ring modified Spongistatin 1 analog with retained picomolar potency among a group of C(15) ester derivatives.

Here, the relationship between unfolding and amyloid aggregation of glaucoma-associated myocilin is probed, showing that myocilin is not at equilibrium and pathogenic aggregation competes directly with unfolding.

Computational methods for the de novo design of conformationally restricted peptides produce exceptionally stable short peptides stabilized by backbone cyclization and/or internal disulfide bonds that are promising starting points for a new generation of peptide-based drugs.

A prespecified analysis of the DELIVER clinical trial shows that the sodium/glucose cotransporter 2 inhibitor dapagliflozin benefits patients categorized as having heart failure with improved ejection fraction, a class of patients at high risk of cardiac events but for which limited treatment data are available.

Improving the stability of proteins for biotechnological applications is challenging. Now, Gillam and co-workers show that the thermal stability and longevity of enzymes can be remarkably enhanced in a single step from sequences of recent ancestors of primitive vertebrates that existed in mild conditions.

Super-resolution imaging of the dynamics of organelle structures in live cells is facilitated by blinking, far-red dyes.

The allocation of remaining fossil fuel production has stimulated a discussion around issues of equitable allocation but the implications of different options are unclear. Here the authors show that shifting production to low-medium human development regions has limited economic benefits under strong climate policy.

The viral Protein Kinase-1 (PK-1) phosphorylates the regulatory protein p6.9, which facilitates baculoviral genome release. Here, the authors combine X-ray crystallography with biophysical and biochemical analyses as well as molecular dynamics simulations to characterize Cydia pomenella granulovirus PK-1, which forms a dimer with a parallel side-to-side arrangement of the kinase domains and furthermore, they provide insights into its catalytic mechanism and evolutionary relationships with other kinases.

Spin waves can provide efficient alternatives to microelectronics in applications such as image processing, but are difficult to realize on the nanoscale. Here, the authors develop a magnonic grating coupler, which allows for the conversion of microwaves to short-wavelength spin waves with large amplitudes.

The strange metal phase in unconventional superconductors is probed by Hall measurements. This reveals that quantum criticality drives the Hall effect, which also correlates with the superconductivity. This indicates that all three may be linked.

Superconductivity is often destroyed under magnetic field larger than a critical value called Pauli limit. Here, the authors report superconductivity beyond the Pauli limit in bulk single crystals of NbS₂, suggesting the development of a Fulde-Ferrell-Larkin-Ovchinnikov state.