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Aortic aneurysm and dissection are lethal vascular diseases lacking effective medical therapy. Here the authors show that calcium channel blocker use increases AAD risk, worsens disease progression in models and patients, and may impair post-repair outcomes, warranting caution in at-risk hypertension.

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.

Human-specific molecular and cellular regulatory programs prolong prefrontal cortical maturation by orchestrating postnatal development of neurons and glia, with implications for cognitive function and susceptibility to neurodevelopmental disorders.

Western boundary currents flow along the western edge of subtropical oceans, transporting heat polewards, and are integral in the climate system. Using high-resolution models, this work shows that western boundary currents will shift shorewards as a result of increased stratification driven by climate change.

Striatonigral neurons comprise diverse subtypes, yet their specific roles in locomotion regulation are not fully understood. Here, authors demonstrate that the Calb1+ subtype promotes locomotion, while the Kremen1+ subtype terminates ongoing movement by inhibiting the activity of Aldh1a1+ dopaminergic neurons via GABBR1 receptors.

2- arachidonoylglycerol (2-AG), an abundant endocannabinoid in the brain, regulates diverse neural functions. Here, the authors identified four loss-of-function mutations in dicylglycerol lipase β (DAGLB) from six patients with early onset Parkinsonism. In mice, loss of DAGLB in dopamine neurons reduced neuronal activity and impaired locomotor function and augmentation of 2-AG levels boosted neuronal activity and rescued locomotor deficits.

Chang’e-6 mission’s analysis of farside lunar soils reveals stronger magnetic properties than nearside samples and identifies distinct magmatic and impact-formed minerals. This offers insights into the Moon’s magnetic history and crustal anomalies.

Rooftop photovoltaic systems are often seen as a niche solution for mitigation but could offer large-scale opportunities. Using multi-source geospatial data and artificial intelligence techniques, the authors map their potential for reducing global temperatures and analyse regional differences.

Chromosome-level genome assemblies of three Allium crops (onion, garlic and Welsh onion) and spatial RNA sequencing provide insights into Allium trait evolution and gene expression patterns during onion bulb formation.

This study uses available models to show intensified Atlantic multidecadal variability under global warming. Warmer and fresher waters, along with slowed overturning circulation, reduce the mixed layer, intensifying sea surface temperature variability, suggesting increased global climate extremes.

The authors find a reversal in El Niño sea surface temperature variability under persistent greenhouse warming, from an increase pre-2100 to a reduction post-2100 amid the development of a permanent El Niño-like warming pattern.

Using a high-resolution model forced under a high emission scenario, the authors find an increase in subsurface marine heatwaves, and in concurrent surface and subsurface marine heatwaves, which can restrict refuge options of marine organisms.

The authors show that the influence of the western Indian Ocean on Antarctic sea ice variability in austral spring has been weakening under greenhouse global warming.

The association between certain mitochondrial DNA variants and increased risk of late-onset diseases in humans could be explained by a direct role of mitochondrial DNA in the regulation of cellular proteostasis.

Metabolic changes often occur during the early stages of cancer development. Here, the authors develop metabolomics signatures from tissues, pre- and post-operative sera and urines in esophageal squamous cell carcinoma, which may aid in early diagnosis.

Over 80% of the global increase in hot extremes is anticorrelated with baseline temperature variability, according to analyses of multi-model climate simulations.

BRAF drives MEK/ERK activation to facilitate tumorigenesis. Here, the authors show that in response to pro-inflammatory cytokines, ITCH mediates a non-proteolytic ubiquitination and activation of BRAF, which in turn sustains MEK/ERK signaling to facilitate melanoma cell growth.

Chiral materials with strong and tunable chiroptical activities are highly desirable. Here, the authors employ an AI-guided robotic platform to fully execute a cyclic process to perform inverse design and fabricate chiral films with target chiroptical performance.

Sea surface temperature variability of the equatorial Pacific Ocean dictates the strength of El Niño–Southern Oscillation events. CMIP6 models under four IPCC emission scenarios show increased variability in the 21st century from the 20th century.

The advancement of high entropy alloy development is both rapid and challenging. Here, the authors discover an unusual Sabatier principle operating on the high entropy alloy surface, which leads to a notable enhancement in catalytic activity for hydrogen evolution reactions.

Analysis of climate models under future greenhouse-gas forcings shows that the frequency of consecutive La Niña events will increase, driven by ocean–atmosphere feedbacks that slow the heat recharge of the equatorial Pacific.

The Atlantic Niño/Niña is an important mode of tropical climate variability, but how it changes with global warming is not clear. Here the authors use a comprehensive model ensemble to show that the Atlantic Niño/Niña system will probably weaken under greenhouse warming.

Under global warming, increased variability in El Niño sea surface temperature was projected to be detectable by about 2070. Here the authors show that the increased variability of a type of more impactful El Niño events is likely detectable by 2030.

The ocean absorbs atmospheric heat; understanding this process is needed to predict climate change impacts. Model analysis shows the influence of the El Niño–Southern Oscillation (ENSO) on Southern Ocean heat uptake—projections with larger (smaller) ENSO amplitude show less (more) ocean warming.

Severe winter air pollution events, attributed to emissions from development, have increased in Beijing in recent decades. This study looks at how atmospheric conditions contribute and projects climate change will increase conditions favourable to such events.

An analysis indicates that the warm, powerful currents that flow along the western edges of ocean basins warmed more than twice as quickly than the global ocean as a whole over the past century. This enhanced warming could have important effects on climate because these currents affect the air–sea exchange of heat, moisture and carbon dioxide.

Extreme La Niña events occur when cold sea surface temperatures across the central Pacific Ocean create a strong temperature gradient to the Maritime continent in the west. This work projects an increase in frequency of La Niña events due to faster land warming relative to the ocean, and a greater chance of them occurring following extreme El Niño events.

Extreme El Niño events cause global disruption of weather patterns and affect ecosystems and agriculture through changes in rainfall. Model projections show that a doubling in the occurrence of such extreme episodes is caused by increased surface warming of the eastern equatorial Pacific Ocean, which results in the atmospheric conditions required for these event to occur.

The impacts of climate change on certain aspects of the El Niño/Southern Oscillation (ENSO) have been established. However, the change in sea surface temperature, commonly used to represent ENSO amplitude, remained uncertain. Now, the sea surface response is shown to be time-varying, with an increasing trend to 2040 followed by a decreasing trend. The previous uncertainty is attributed to the expectation of unidirectional behaviour and unrealistic model representations.

The SEED study is a phase 3 clinical trial demonstrating a beneficial effect on glycemic control of dorzagliatin, a glucokinase activator, in drug-naive patients with newly diagnosed type 2 diabetes.

CMIP5 simulations reveal that the frequency of extreme El Niño events doubles under the 1.5 °C Paris target, and continues to increase long after global temperatures stabilize due to emission reductions. Extreme La Niña events, however, see little change at either 1.5 °C or 2 °C warming.

The North Pacific Meridional Mode (NPMM) can trigger El Niño/Southern Oscillation (ENSO) events. Climate simulations suggest that with warming ocean temperatures, the NPMM’s impact on future ENSO strengthens, contributing to increased frequency of future extreme ENSO events and their predictability.

Despite inter-model differences in predicting the details of the eastern Pacific El Niño, a robust increase in the corresponding sea surface temperature variability under greenhouse warming is found across models.

The strength of a positive Indian Ocean Dipole (pIOD) is set by sea surface temperature gradient across the equatorial Indian Ocean. Modelling shows warming will increase strong pIODs but decrease moderate pIODs, as faster surface warming in the west sets up conducive conditions for the strong events.

Modelling experiments show that the El Niño response to global warming is self-modulating and depends on its historical variability; if current variability is high, future variability will be low.

It is unclear how extreme positive Indian Ocean Dipole will respond to 1.5 °C of warming. Here the authors show that the frequency of these events increases linearly with warming, doubling at 1.5 °C from the pre-industrial level, but plateaus thereafter.

Extreme positive-Indian-Ocean-dipole events cause devastating floods in eastern tropical Africa and severe droughts in Asia; increasing greenhouse gas emissions will make these dipole events about three times more frequent in the twenty-first century.

Submesoscale ocean eddies inhibit the growth of La Niña and El Niño events, according to an analysis of long-term high-resolution global climate simulations.

Understanding the impact of future marine heatwaves on coastal ecosystems, which account for most of global fishery catches, is limited due to low-resolution models. Use of high-resolution models shows increases in intensity, and the number of days, of marine heatwaves, endangering resident species.