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The San Andreas Fault is weak compared with the surrounding rock, but the cause of weakness is debated. Measurements of the strength of rocks taken from the active fault indicate that the San Andreas Fault is inherently weak and does not heal after rupture, causing it to slip aseismically in central California.

A post hoc analysis of a multicentre, randomised trial showed that prediabetes remission is possible without total weight loss—providing weight is distributed to subcutaneous deposits as opposed to visceral ones.

Here authors used patient-derived forebrain organoids to reveal how LIS1 mutations cause varying severity in a neurodevelopmental disorder, uncovering links between cytoskeletal defects, protein stress, and potential therapeutic strategies.

Better predictions of earthquake likelihood will be possible only by understanding the physics of faults in the Earth’s crust. But the subject is a tough one. For example, although a new model of the characteristics of the San Andreas fault in California is consistent with some aspects of the available data, it does not account for others.

Viruses such as coxsackievirus B (CVB) have been associated with type I diabetes (T1D) and islet destruction. Here the authors show that Yes-associated protein (YAP) is upregulated in the whole pancreas in T1D and at-risk autoantibody (AAb + ) organ donors and that YAP over-expression enhances CVB replication, islet inflammation and β-cell apoptosis and suggest exocrine-islet-immune interactions as targeted interventions for T1D.

Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

Using data from the CoVPN 3008 study, the authors show that the neutralizing antibody correlate of risk holds in people living with HIV. However, the nAb correlate was weaker and shorter-lived in a vaccine-immunity versus hybrid-immunity population.

The authors in this work identify an in vivo CNS active bifunctional degrader of GSK3. This was discovered via development of orthogonally reactive linker chemistry and a direct-to-biology screen that was able to provide hits of in vivo chemical probe quality.

PROTACs induce degradation by bridging a target protein and E3 ubiquitin ligase. Here, authors show that protein interface frustration correlates with cooperativity, offering a structural metric to prioritize PROTAC candidates prior to synthesis.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Natural product–inspired compounds are primed to interact with and manipulate biological processes, but obtaining these complex molecules poses synthetic challenges. The development of a 12-step, 1-pot cascade reaction leads to the 'centrocountins', tetrahydroindoloquinolizines that modulate mitosis by targeting the centrosome-associated proteins nucleophosmin and Crm1.

A purpose-built implantable system based on biomimetic epidural electrical stimulation of the spinal cord reduces the severity of hypotensive complications in people with spinal cord injury and improves quality of life.

There is no universal model for large earthquake recurrence, and an ensemble forecasting approach is desirable when dealing with paleoseismic records with few data points and large measurement errors.

Two-qubit operations exceeding 99% fidelity have been demonstrated by silicon devices made with standard semiconductor tooling in a 300-mm foundry environment.

African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

A systematic review and meta-analysis of clinical trials investigating the efficacy and safety of obesity management medications reported tirzepatide and semaglutide to be the most effective in reducing body weight and obesity-related complications.

The authors report a meta-analysis of methylome-wide association studies, identifying 15 significant CpG sites linked to major depression, revealing associations with inflammatory markers and suggesting potential causal relationships through Mendelian randomization analysis.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

In a phase 1/2a umbrella trial in patients with glioblastoma matching targeted therapies according to tumor molecular profiling, temsirolimus plus radiotherapy improved PFS compared to standard of care in patients with phospho-mTOR activation.

A large brain imaging study of over 2000 people worldwide shows that fear conditioning engages brain regions linked to emotion and attention, with differences in individuals with anxiety or depression and strong influences from task design.

Analysis of samples from the asteroid Ryugu provide evidence of late fluid flow in a carbonaceous asteroid, indicating that such bodies may have retained two to three times more water than previously thought.

Surprisingly consistent replication failure of gray matter correlates of childhood maltreatment raises questions about publication bias in prior literature and about prevailing models linking maltreatment to brain structure in adult populations.

17β-oestradiol establishes an anti-ferroptotic state in female kidney tubules.

A comprehensive understanding of how urban nature affects mental health at a global scale remains essential. This study addresses that need through a systematic review and meta-analysis, revealing the effects of exposure to various urban nature types on 12 distinct mental health outcomes.

A retrospective, observational study shows that completion of a diabetes prevention program in England (the NHS Diabetes Prevention Programme) was associated with decreased incidence of type 2 diabetes and long-term conditions such as dementia and chronic obstructive pulmonary disease at 24 months.

Polyneuropathy causes are difficult to pinpoint. Here, authors used single-nucleus and spatial transcriptomics of 37 human peripheral nerves to identify focal perineurial hyperplasia and endoneurial lipid-associated macrophages in polyneuropathies.

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.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

Lung cancer screening effectiveness can be subject to variation based on personal risk factors. Here the authors report that heterogeneity in lung cancer screening effectiveness is primarily driven by histology.

Sand spikes, sandstone bodies that have been enigmatic for nearly two centuries, represent a new type of seismite and a promising tool to identify strong impact-induced or tectonic paleo-earthquakes and their source regions in the geologic record.

The study reveals strikingly different nonlinear Rabi splitting dynamics in MoSe₂ monolayers and (Ga,In)As quantum wells, highlighting the pivotal role of Coulomb interactions in shaping light–matter coupling in two-dimensional semiconductors.

It is unclear whether the linkage between tree species richness and insect herbivory is consistent across climates and forest types. Here, the authors analyse data from forest biodiversity experiments to show a generally positive tree growth–insect herbivory relationship that is modulated by leaf traits.

Iceberg calving can act as a submarine melt amplifier through excitation of transient internal waves.

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

Copper-based organic light-emitting diodes are low-cost alternatives to precious metal-based counterparts. Here, the authors develop copper(I) thermally activated delayed fluorescent emitters with colors spanning from blue to near infrared, and achieve device lifetime close to 3700 h at 1000 cd/m².

Interact-omics, a high-throughput cytometry-based framework, resolves the cellular interaction landscape.

Here the authors report single-cell and spatial transcriptomics of young and aged male fibrotic mouse lungs. Age-related alterations in capillary sub-populations are associated with a proangiogenic phenotype linked to regeneration of the alveolar niche.