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SARS-CoV-2 variants often exhibit immune evasion, necessitating antiviral strategies beyond vaccination. This study presents a papain-like protease (PLpro) inhibitor called YL1004, which exhibits potent, broad-spectrum antiviral activity against wild-type, Delta, and Omicron variants in vitro and in vivo.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Some cancer cells exhibit high loads of reactive iron in lysosomes, and this feature is exploited by using fentomycin-1, a newly developed small molecule, to induce ferroptosis.

Cellular uptake of copper(ii) by CD44 has a key role in regulating cellular plasticity via copper(ii)-dependent downstream signalling events.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

A rationally designed assay detects granzyme A activity by integrating peptide-based GzmA-targeted inhibitors and probes with chemiluminescent reporters to monitor inflammatory bowel disease.

Histone post-translational modifications control several fundamental processes on DNA. Here, the authors describe a conserved phosphorylation of histone H3 on the globular core and show that it loosens the nucleosome and regulates DNA repair.

In this study, Marlin et al. provide insights into the potential use of subunit vaccines that induce a high level of protection against SARS-CoV-2 in animal models.

Satellite altimetry reveals intensifying global river water level variability (2016–2024) through increased seasonality, reduced seasonal fluctuations, and escalating hydrological extremes, signaling dual stress from concurrent droughts and floods.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Measuring relative frequencies of DNA double-strand breaks between loci does not provide the full physiological relevance of those breaks. Here Rowicka and colleagues present qDSB-Seq method which uses spike-in double-strand breaks induced by a restriction enzyme to accurately quantify DNA damage.

Npm1 promotes tumor formation via attenuating the integrated stress response and p53 activation in mouse WNT-driven intestinal and liver tumorigenesis.

The dynamics and durability of immune responses associated with protection against symptomatic infection in children offer insights to guide vaccination policies in pediatric populations.

Obesity is associated with an elevated risk of prostate cancer. Here, the authors show that periprostatic adipose tissue promotes the migration and local invasion of prostate cancer cells by secreting the chemokine, CCL7, and that this process is enhanced in the context of obesity.

Arctic sea ice loss is reshaping the ocean’s carbon pump. Satellite data show an early boost, then stagnation, while models warn of future weakening under ice-free conditions, threatening carbon storage and ecosystems.

SAMHD1 has an essential role in the replication stress response and prevents inflammation by activating the MRE11 nuclease to degrade nascent DNA strands at stalled replication forks, thus enabling replication.

Nonselective engagement of GPCR signaling pathways by GPCR-targeting drugs can reduce treatment efficacy and cause side effects. The authors show that signaling selectivity in CB2R can be tuned by reshaping allosteric networks, offering insights for more precise therapies.

In this study, the authors generated iPSC lines from more than 100 sporadic ALS cases, which recapitulated key disease phenotypes and enabled large-scale drug screening, identifying a promising combination therapy of baricitinib, memantine and riluzole.

Epigenetic modifications are a key contributor to cell identity, and their propagation is crucial for proper development. Here the authors use a super-resolution microscopy approach to reveal how histone variants are faithfully transmitted during genome duplication, and reveal an important role for the histone chaperone ASF1 in the redistribution of parental histones.

Here they show that mitochondria-localized NEK7 couples mitochondrial complex II subunit SDHB to maintain the homeostasis of electron transport in hepatocytes, thereby impeding the progression of liver fibrosis.

It is unclear how early-life urbanicity influences adult neurobehavioral traits. This study reveals that earlier menarche mediates the relationship between early-life urbanicity and adult neurobehavioral traits associated with mental disorders.

Here the authors find that erythroblasts of myelodysplastic syndromes with SF3B1 mutation leading to inefficient erythropoiesis show DNA replication stress with accelerated forks and reduced R-loops. Restoring R-loops by a histone deacetylase inhibitor rescues erythroid differentiation.

BRCA1 is a key breast and ovarian cancer suppressor involved in DSB repair. Here, the authors show that cells heterozygous for several BRCA1mutations are universally defective in the response to replication stress, which could contribute to the BRCA1 breast cancer development pathway.

Senescence of hematopoietic progenitor cells, enforced by the BRAF^V600E mutation, underlies the development of Langerhans cell histiocytosis and could be a new target for drug development and therapy of this disease in patients.

Viruses such as EBV use various mechanisms to avoid antiviral responses. Here the authors propose that the EBV protein BRRF2 is secreted via extracellular vesicles from NPC cells, disrupts the cGAS-STING pathway, reduces cGAS-DNA phase separation and the subsequent antiviral response.

Viral diversity and abundance in bats are incompletely understood. Here, analyzing individual bat viromes, the authors observe a high frequency of co-infection and spillover among the animals and identify viruses with the potential to infect humans or livestock.

The spike protein of the Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 than Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic and vaccine-elicited neutralizing antibodies.

Using degron approaches, the authors show that cancer cells experiencing prolonged DNA methylation loss—without substantial DNA damage—undergo non-canonical senescence. This has important potential implications for cancer treatment.

Bats harbor diverse viruses but it’s less clear how they tolerate infection. Here, by characterizing innate immune responses in bat cells the authors show that IFN-beta signaling resists antagonistic activity by viruses and identify interferon stimulated genes with enhanced antiviral activity.

Theulot et al. introduce NanoForkSpeed, a nanopore sequencing-based method to map individual replication fork velocities on entire genomes. NFS shows that fork speed is uniform across yeast chromosomes except for a marked slowdown at pausing sites.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

The Spp1 subunit of Set1C is recruited to the Tus/Ter replication fork barrier via its PHD domain and protects the replication fork by preventing excessive ssDNA formation, stressing the importance of chromatin structure in the replication stress response.

Streptomyces bacteria have a linear chromosome and a complex life cycle, including development of multi-genomic hyphae that differentiate into mono-genomic exospores. Here, Szafran et al. show that the chromosome of Streptomyces venezuelae undergoes substantial remodelling during sporulation, from an ‘open’ to a ‘closed’ conformation.

Lymphatics maintain lipid transport, immunity, and fluid balance. Kim J and Chaudhary S et al. reveal an AIBP-driven cholesterol efflux mechanism that regulates lymphangiogenesis via VEGF signaling.

Here, the authors describe the emergence and spread of a new potential SARS-CoV-2 variant of interest, B.1.620. They show that this lineage, first identified in Lithuania, has established local transmission in Europe on multiple occasions and likely emerged in Central Africa.

Deep-sea sediments are a key sink for molybdenum (Mo). Here it is found that the their isotopic composition is heavier than typical endmembers; refining the global Mo budget, and improving reconstructions of past ocean oxygen levels.

Going from model development to a pilot implementation study, a deep learning model shows that acute aortic syndrome can be diagnosed directly from noncontrast CT, increasing accuracy and decreasing time to diagnosis.

In most bacteria and archaea, a broadly conserved mitotic-like apparatus assures the inheritance of duplicated genetic material before cell division. Here, the authors use super-resolution microscopies to dissect the activities required for proper DNA segregation through the nucleoid interior.

Therapeutic administration of angiopoietin-like 4 prevents shock during Neisseria meningitidis infection or lipopolysaccharide-induced sepsis in mice.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

Sodium-ion batteries are emerging as a complementary technology to lithium-ion batteries, but are not yet ready for widespread practical adoption. This Review provides an overview of various sodium-ion chemistries with respect to key criteria, including sustainability, before discussing potential solutions, market prospects and future work.

In this randomized, controlled integrated phase 1/2/3a/3b clinical trial, the authors show that the self-amplifying mRNA COVID-19 vaccine ARCT-154 shows good immunogenicity and is safe and efficient against COVID-19 (57% against any COVID-19, and 95% against severe COVID-19).

Oncogene-induced replication stress (RS) promotes cancer development. Here, the authors report that cancer cells adapt to oncogene-induced RS by overexpressing downstream components of ATR-CHK1 pathway, Claspin and Timeless, which have protective role at the replication forks independent of their checkpoint function.