Proceedings of the National Academy of Sciences

A pharmacovigilance data–driven approach to reveal high fatal adverse events following checkpoint immunotherapy

Immune checkpoint inhibitors (ICIs) have significantly improved the outcome of cancer treatment, but they also expose most patients to a variety of treatment-related adverse events (AEs). This study i...

Elites moved toward democrats more than nonelites moved away: Income, education, and occupational class in US presidential elections, 1980–2020

Recent discussion of voting in US elections claims a strong movement of White working-class voters away from voting for Democrats, with much discussion focusing only on elections between 2012 and the...

Broadly applicable hydrophilic additive enhances electrochemical transistor function

Organic semiconductors offering efficient mixed ionic-electronic charge transport are key components of organic electrochemical transistors (OECTs) needed for future bioelectronics and other technolog...

How and why avian reproductive success varies in response to precipitation: A global meta-analysis

Precipitation influences animal physiology, behavior, and ecological interactions, therefore affecting demography. However, the nature and strength of those effects vary widely, have been attributed t...

A distinct subclade of AlkB family demethylases in ciliates safeguards the positional fidelity of eukaryotic N ⁶ -methyladenine (6mA)

DNA N 6 -methyladenine (6mA) is a newly recognized transcription-associated epigenetic mark in eukaryotes. While its methylation pathway has been well establish...

Extended local anesthesia enabled by flavonoid permeation enhancers

Site 1 sodium channel blockers (S1SCBs), such as tetrodotoxin (TTX) and neosaxitoxin, are ultrapotent local anesthetics with low tissue toxicity. Their duration of action is relatively brief, but incr...

Dynamic reprogramming of the tumor immune network via multicycle checkpoint degradation for cancer immunotherapy

The efficacy of immune checkpoint blockade is often limited by intrinsic immunosuppressive networks within the tumor immune microenvironment (TIME). Despite progress in cancer treatment, current extra...

Coupling of functionality to trafficking of KCNQ2/3 potassium channels at the axon initial segment

KCNQ2/3, a major voltage-gated potassium channel at the axon initial segment (AIS), plays a crucial role in controlling neuronal excitability. While the functionality of KCNQ2/3 is regulated by confor...

Pri micropeptide functions as a cell-intrinsic timer controlling the transient phase of cell fate induction

During development, cells sequentially acquire specific fates through temporally ordered regulatory systems. To ensure the harmonious progression, each system must be activated and subsequently inacti...

Reply to Yang et al.: Synergies between photovoltaic development and innovative agricultural practices for combating desertification

Reply to Pernet et al.: Mesocosm experiment reveals the carbon removal mechanisms in oyster farming

Scientific evidence does not support oyster farming as a marine carbon dioxide removal strategy for climate mitigation

Profile of David Baker, Demis Hassabis, and John Jumper: 2024 Nobel laureates in Chemistry

The 2024 Nobel Prize in Chemistry recognized revolutionary computational success in predicting protein structures from amino acid sequences and for designing amino acid sequences that fold into desire...

Detectable global temperature responses to wildfires and volcanic eruptions

Large volcanic eruptions and intense wildfires perturb Earth’s atmospheric temperature. Understanding the climate response to such natural forcings is essential for obtaining reliable estimates of its...

Altermagnetic polar metallic phase in ultrathin epitaxially strained RuO ₂ films

Altermagnetism refers to a wide class of magnetic orders featuring magnetic sublattices with opposite spins related by rotational symmetries, resulting in nontrivial spin splitting and magnetic multip...

Primary biomolecular adsorption energetics of core–shell nanocomplexes: Implications for biological interactions

Molecular organization at the nano-bio interface governing the colloidal stability, reactivity, immune recognition, and drug delivery performance of nanoparticles remains difficult to predict. Quantif...

D-amino acid aminotransferase1 regulates grain chalkiness in rice by modulating endoplasmic reticulum stress response

D-amino acids are key components of the bacterial cell wall and play important roles in neural communication and inflammatory responses in animals. However, knowledge about D-amino acid metabolism and...

Reverse engineering what makes a symbol memorable

Symbols may represent the first form of human visual communication, yet little is known about the cognitive and neural mechanisms supporting memory for these pervasive graphics. By investigating memor...

The geometry of Nature’s stingers is universal due to stochastic mechanical wear

Despite their ubiquity in Nature, spikes or stingers rarely exhibit sharp tips. Instead, a closer inspection of their roughly conical tips reveals a striking similarity in their profiles: They adhere...

GalNAc-T13 maintains neurite architecture and memory retention via O-GalNAc glycosylation of seizure protein 6

Glycosylation, a key and prevalent modification in brain proteins and lipids, is essential for brain development and function. O-GalNAc glycosylation, initiated by the family of polypeptide N-acetylga...

Agile legged locomotion in reconfigurable modular robots

Legged machines are becoming increasingly agile and adaptive, but they have so far lacked the morphological diversity of legged animals, which have been rearranged and reshaped to fill millions of nic...

Unveiling hidden intermediate states in protein folding with AI-based conditional transition clustering

Revealing the complex mechanisms of protein folding, including the transient intermediate states that govern the process, is a fundamental goal in computational biophysics. While molecular dynamics (M...

Mechanical performance of hybrid polymer–lipid vesicles with leaflet asymmetry engineered using microfluidics

Lipid vesicles consist of aqueous cores surrounded by a bilayer of phospholipids. Hybrid polymer–lipid vesicles incorporate both polymers and lipids, offering promising properties for developing pharm...

Dissecting spatial patterning and signaling with directional diffusion in spatial multi-omics

Spatial multi-omics sequencing enables the simultaneous profiling of transcriptomics, proteomics, and epigenomics at a spatial resolution, offering insights into complex tissue organization and molecu...

Fear extinction induces maladaptive generalization via noradrenergic and GABAergic systems

Exposure therapy for anxiety disorders relies on fear extinction to reduce pathological fear responses. Here, we show that while effective at diminishing conditioned fear, extinction training paradoxi...