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Hepatitis C virus remains a health burden due to the lack of an effective vaccine, hindered by difficulties in replicating the native E1E2 antigen structure. Here, the authors engineer a stabilized E1E2 heterodimer using cryo-EM-guided modifications, enhancing immunogenicity and paving the way for future HCV vaccine development.

Climate action could avoid over 1 million deaths globally from air pollution in 2040. However, it is suggested that cooperation is needed between developed and developing nations to ensure that disparities in air pollution are not perpetuated in the future.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

This study shows that the Snowflake mutant in clownfish results from altered communication between pigment cells, producing enlarged white bars with jagged edges. It points to cell–cell communication as a driver of color pattern diversity in fishes.

Borneol has repelled mosquitoes for millennia, but how it worked was unknown. Here, the authors show the sensory pathway mosquitoes use to detect and avoid this ancient plant compound, opening the door to improved natural repellents.

Brief ultrasound to human frontal eye fields, but not motor cortex, rapidly biases eye movement contralaterally in a perceptual choice task. The size of this effect scales with individual baseline FEF inhibitory tone.

Here the authors identify nicotine-derived inhibitors of the SARS-CoV−2 main protease that outperform Paxlovid in cells and mice, remain effective against resistant variants, and show broad activity against multiple human coronaviruses.

The authors show that aging of metastable protein condensates can lead to amyloid formation and impair biochemical activity. Certain small molecule metabolites can selectively impede this transition, preserving condensate function.

Using a random regression model, the study shows there are varying genetic profiles that act on BMI from infancy to adolescence. Change in BMI across childhood is genetically correlated with several adult cardiometabolic traits.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

This study shows that mithramycin suppresses the EWS::FLI1 transcription factor in Ewing sarcoma using a hybrid CUT, Tag & GRO assay, revealing mechanism, need for continuous dosing, and supporting clinical use of next-gen analog AIT-102.

Neoantigen-based adoptive T cell therapies represent a personalized approach for cancer immunotherapy. Here the authors describe NEO-STIM, an ex vivo T cell induction platform to STIMulate peripheral blood T cells to generate responses against tumor NEOantigens.

Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into molecular glue degraders.

DNA recognition and cleavage control in type II topoisomerases are poorly understood processes. Here, the authors determine cleaved and uncleaved structures of supercoiled DNA-bound topoisomerase VI that reveal how the enzyme activates its cleavage state and prefers to act at deformable substrates.

Amundsen Sea records show warm Circumpolar Deep Water drove major West Antarctic Ice Sheet retreat from 18,000–10,000 years ago. Subsequent cooling stabilized the grounding line, indicating ocean heat—not atmospheric warming—controlled long-term WAIS change.

Pertussis notifications reduced during the COVID-19 pandemic in the Netherlands but increased in 2023 to the highest levels since vaccination introduction. Here, the authors use longitudinal serological data from a nationwide cohort study to investigate waning immunity and infection incidence.

The transformations for aragonite precursors in coral are not fully understood but have implications in bio, biogenic and geological mineralization. Here, the authors use high-resolution mapping and observe exponential decay from the edge of four precursors to coral aragonite skeleton in Stylophora pistillata.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

A measurement strategy is described that is able to read out the parity of minimal two-site Kitaev chains in real time, by coupling two Majoranas and resolving their quantum capacitance.

Fibrosis is the final common pathway in chronic kidney disease and a potential target for therapeutic interventions. Here, the authors use intravital imaging to show that pyrimidinergic calcium signaling links tubular injury to fibroblast activation, and that blocking this pathway reduces fibrosis

Mucosal administration of a multivalent, adjuvanted vaccine against Clostridioides difficile promoted bacterial clearance and protected against morbidity, mortality, tissue damage and recurrence in mice.

The paper reports a scalable, chemical-free plasma process that converts methane and water into high-purity, single-layer graphene oxide while co-producing hydrogen, cutting greenhouse emissions, and lowering cost compared with conventional methods.

The ferroelectric nematic phase has both spontaneous polarity and fluidity and is therefore desirable, but can be challenging to obtain. Here, the authors report the preparation of a number of ferroelectric nematogens, of which several show the phase transition at relatively low temperatures.

The authors find that distinct radial glia subtypes generate and support midbrain dopaminergic neurons, revealing specialized function and lineage relationships among the diverse cell types that shape dopamine neuron development.

This Reusability Report tests the ability of a foundation model, ActFound, to predict the antibacterial activity of plant natural products. We found that although all models performed poorly on this task, ActFound performed better than similar models.

How the brain maintains object representations during grasping, when complex sensory input rapidly changes, remains poorly understood. Here the authors show that object-identity signals shift and strengthen across sensorimotor cortex as reaching transitions to grasping.

Anthropogenic nitrogen enrichment reduces symbiotic nitrogen fixation, but environmental factors alone cannot explain this response. This meta-analysis shows that integrating both environmental factors and plant performance traits improves the predictive accuracy of symbiotic nitrogen fixation responses by 42.7%.

Autopsy brain studies can be distorted because time and temperature alter gene expression. Here, the authors show that neurons, then oligodendrocytes, sequentially activate artifact genes, and provide a tool to measure these effects in RNA sequencing data.

Mechanical response of semiconducting polymers affects their electrical properties, yet the detail remains elusive. Zhong et al. examine the multiscale structural evolution of conjugated polymer thin films during uniaxial deformation and link it to mechanical resilience and solar cell performance.

Cardiac rhythm depends on tightly regulated sodium channel gating. Here, the authors determine the structure of human Na_v1.5 in an intermediate open state and show how specific N-terminal interactions and ion binding near the IFM motif together regulate fast inactivation.

CRISPR-Cas12a catalyses RNA-guided DNA cleavage. Here, authors present structure-function studies of a high-fidelity Cas12a variant that reveal how helical transition of a conserved “bridge helix” facilitates R-loop propagation and DNA cleavage.

Plants require the plastid encoded RNA polymerase PEP to generate viable photosynthetic apparatus. Here the authors genetically engineer an optoswitch that enables photo-induced complementation of an albino mutant restoring transcription and chloroplast biogenesis on demand.

Population-level analyses and in vitro experiments show that a specific genetic variant of cyclin D3 inhibits the growth of the malaria-causing parasite Plasmodium falciparum in erythrocytes, and suggest that its high frequency in Sardinia was driven by past endemic malaria.

Exhaustion is a functional state that hampers anti-cancer and antiviral CD8 T cell activity, and is preceded by a stem-like state, maintained by the transcription factor TCF1. Here authors develop mouse models that allow a precise understanding of the developmental trajectory between the stem-cell-like and exhausted states of CD8 T cells and find that while constitutive overexpression of TCF1 expands the stem-like T cell pool, TCF1 expression specifically in already exhausted cells is unable to promote dedifferentiation.

Supersolid phases are quantum-entangled states of matter exhibiting the dual characteristics of superfluidity and solidity. Here, the authors map the phase diagram of K₂Co(SeO₃)₂. and identify signatures of two supersolid phases separated by a 1/3 magnetization plateau.

ASXL1 is often mutated in myeloid cancers. Here, the authors describe the molecular and structural mechanism by which ASXL1 associates with the transcriptional coactivator BRD4, helping to explain their high correlation in cancers.

PARP1 is a first responder to DNA damage. Here, multiple cryo-EM strategies and biophysical tools analyze PARP1 and partner HPF1 detecting a DNA break, revealing a striking mobility of the PARP1 catalytic domain relative to the DNA binding domains.

Taxanes, such as docetaxel or cabazitaxel, are one of the few chemotherapy options for metastatic castration-resistant prostate cancer (mCRPC). Here, the authors discover that FOXJ1 modulation of microtubule dynamics regulates resistance to docetaxel in mCRPC.

The limited tunability of threshold voltage is a major obstacle for applying two-dimensional transistors in post-silicon electronics. Here, the authors show that bimetallic thiophosphates, such as LiInP₂S₆, enable programmable threshold voltages in both n-type and p-type 2D transistors, leading to low-power, high-speed complementary logic inverters.

Little work has been done to describe and address the variability inherent in the agroinfiltration and genetic engineering of Nicotiana benthamiana. Here, the authors identify and quantify the sources of virtually all variation and develop recommendations for minimizing variation.

Plasma p-tau217 tests used to develop clocks that predict when cognitively unimpaired individuals would develop symptoms of Alzheimerʼs disease.

The combination of within-species variation in pathogen load, the shape of the relationship between pathogen load and infectiousness, and vector feeding preferences shape transmission of multi-host vector-borne pathogens. Here, the authors use experimental and wild bird infection data to characterize the role of 17 host bird species in avian malaria transmission in Hawaii.

The deep learning model STARLING can generate accurate ensembles of intrinsically disordered regions of proteins using only protein sequence as input.

CRISPR/Cas9 screens have identified genetic contributions to many phenotypes. However, studying combinations of genes or regulatory elements remains challenging. Here, the authors use CRISPR/Cas12a to overcome those challenges and enable new approaches to study combinatorial genetic mechanisms.