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AI-Validated Brain Targeted mRNA Lipid Nanoparticles with Neuronal TropismClick to copy article linkArticle link copied!

Targeting therapeutic nanoparticles to the brain poses a challenge due to the restrictive nature of the blood–brain barrier (BBB). Here we report the development of mRNA-loaded lipid nanoparticles (LNPs) functionalized with BBB-interacting small molecules, thereby enhancing brain delivery and gene expression. Screening brain-targeted mRNA-LNPs in central nervous system (CNS) in vitro models and through intravenous administration in mice demonstrated that acetylcholine-conjugated LNPs achieved superior brain tropism and gene expression, outperforming LNP modifications with nicotine, glucose, memantine, cocaine, tryptophan, and other small molecules. An artificial intelligence (AI)-based model designed to predict the BBB permeability of small-molecule ligands showed strong alignment with our experimental results, providing in vivo validation of its predictive capacity. Cell-specific biodistribution analysis in Cre-reporter Ai9 mice showed that acetylcholine-functionalized LNPs preferentially transfected neurons and astrocytes following either intravenous or intracerebral administration. Mechanistic studies suggest that acetylcholine-LNP uptake is mediated by the functional engagement of acetylcholine receptors (AchRs) followed by endocytosis, which synergistically enhances intracellular mRNA delivery. Moreover, acetylcholine-LNPs successfully crossed a human BBB-on-a-chip model, enabling transgene expression in human iPSC-derived neurons. Their effective penetration and transfection in human brain organoids further support their potential activity in human-based systems. These findings establish a predictive and modular framework for engineering CNS-targeted LNPs, advancing precision gene delivery for brain disorders.

Microendovascular Neural Recording from Cortical and Deep Vessels with High Precision and Minimal Invasiveness

Interesting paper where microintravascular electrodes were inserted into cortical veins of pigs to record somatosensory and visual neuronal activity as well as selectively stimulate motor areas. Compared to electrocorticography, this is a less invasive approach with similar capabilities. #neurotech [ https://doi.org/10.1002/aisy.202500487](https://doi.org/10.1002/aisy.202500487)

Intravascular electroencephalography (ivEEG) with microintravascular electrodes enhances neural monitoring, functional mapping, and brain–computer interfaces (BCIs), offering a minimally invasive approach to assess cortical activities; however, this approach remains unrealized. Current ivEEG methods using electrode-attached stents are limited to recording from large vessels, such as the superior sagittal sinus (SSS), restricting access to cortical regions essential for precise BCI control, such as those for hand and mouth movements. Here, ivEEG signals from small and soft cortical veins (CV-ivEEGs) in eight pigs using microintravascular electrodes are recorded, achieving higher resting-state signal power and greater spatial resolution of somatosensory evoked potentials (SEPs) compared to SSS-based ivEEG. Additionally, ivEEG recorded from deep veins clearly captures visual evoked potentials. Furthermore, comparisons between CV-ivEEG and electrocorticography (ECoG) using epidural and subdural electrodes in two pigs demonstrate that CV-ivEEG captures cortical SEPs comparable to ECoG. Targeted electrical stimulation via cortical vein electrodes induces specific contralateral muscle contractions in five anesthetized pigs, confirming selective motor-region stimulation with minimal invasiveness. The findings suggest that ivEEG with microintravascular electrodes is capable of accessing diverse cortical areas and capturing localized neural activity with high signal fidelity for minimally invasive cortical mapping and BCI.

Lasers just made atoms dance, unlocking the future of electronics

Scientists at Michigan State University have discovered how to use ultrafast lasers to wiggle atoms in exotic materials, temporarily altering their electronic behavior. By combining cutting-edge microscopes with quantum simulations, they created a nanoscale switch that could revolutionize smartphones, laptops, and even future quantum computers.

Scientists just found the hidden cosmic fingerprints of dark matter

Scientists at Rutgers and collaborators have traced the invisible dark matter scaffolding of the universe using over 100,000 Lyman-alpha emitting galaxies. By studying how these galaxies clustered across three eras shortly after the Big Bang, they mapped dark matter concentrations, uncovering cosmic “fingerprints” that reveal how galaxies grow and evolve.

Glucose-dependent glycosphingolipid biosynthesis fuels CD8+ T cell function and tumor control

Glucose controls CD8+ T cell function.

The researchers demonstrate that in CD8+ effector T cells, glucose metabolism extends beyond energy production by fueling glycosphingolipid (GSL) biosynthesis, a pathway critical for T cell expansion and cytotoxic function.

The authors show that CD8+ effector T cells use glucose to synthesize uridine diphosphate-glucose (UDP-Glc), a precursor for glycogen, glycan, and GSL biosynthesis. Inhibiting GSL production impairs CD8+ T cell expansion upon pathogen challenge.

Mechanistically, we show that glucose-dependent GSL biosynthesis is required for plasma membrane lipid raft integrity and optimal T cell receptor (TCR) signaling. https://sciencemission.com/Glucose-dependent-glycosphingolipid-biosynthesis

Glucose is required for T cell proliferation and function, but its key metabolic fates in vivo are not well defined. Longo et al. demonstrate that in CD8+ effector T cells, glucose metabolism extends beyond energy production by fueling glycosphingolipid biosynthesis, a pathway critical for T cell expansion and cytotoxic function.

Satellites Detect Mysterious Changes in the Earth’s Core

A team of scientists has detected a colossal geological anomaly, a massive and mysterious change that took place nearly 2,900 kilometers deep, right at the boundary between the Earth’s mantle and the core, an event that measurably altered the planet’s gravitational field and that has been captured, indirectly but unequivocally, by instruments in orbit.

The finding, published last month in the journal Geophysical Research Letters, suggests that the structure of rocks in the depths of the lower mantle can transform dynamically, a process that could have fundamental implications for our understanding of planetary dynamics, from the origin of major earthquakes to the generation of the magnetic field that protects life on the surface.

The research, led by Charlotte Gaugne Gouranton of the City University of Paris and with the notable participation of geophysicist Isabelle Panet of Gustave Eiffel University, focused on the meticulous analysis of data collected by the GRACE (Gravity Recovery and Climate Experiment) satellite mission, a joint project between the United States and Germany that operated between 2002 and 2017.

Forewarned Is Forearmed: The single- and dual-brain mechanisms in Detectors from Dyads of Varying Social Distance During Deceptive Outcomes Evaluation

The study investigates how people (“receivers” / “detectors”) evaluate deceptive information depending on social distance (friend vs. stranger) and context (whether the outcome involves gains or losses).

Receivers were more likely to fall for deception in gain contexts than in loss contexts. That is, when there is a possible reward, people are less vigilant / more prone to be deceived.

Key brain regions involved: Dorsolateral Prefrontal Cortex (DLPFC, risk evaluation), Orbitofrontal Cortex (OFC, reward processing), Frontal Pole Area (FPA, intention understanding). Differences in activity/connectivity in these regions were associated with how people evaluated deceptive vs truthful information, and depending on social distance.

Preventing deception requires understanding how lie detectors process social information across social distance. Although the outcomes of such information are crucial, how detectors evaluate gains or losses from close versus distant others remains unclear. Using a sender-receiver paradigm and fNIRS hyperscanning, we recruited 66 healthy adult dyads (32 male and 34 female dyads) to investigate how perceived social distance modulates the neural basis in receivers (the detector) during deceptive gain–loss evaluation. The results showed that detectors were more prone to deception in gain contexts, with these differences mediated by connectivity in risk evaluation (Dorsolateral Prefrontal Cortex, DLPFC), reward-processing (Orbitofrontal Cortex, OFC), and intention-understanding regions (Frontal Pole Area, FPA). Hyperscanning analyses revealed that friend dyads exhibited higher interpersonal neural synchrony (INS) in these regions than stranger dyads. In gain contexts, friend dyads showed enhanced INS in the OFC, whereas in loss contexts, enhanced INS was observed in the DLPFC. Trial-level analysis revealed that the INS during the current trial effectively predicted the successful deception of that trial. We constructed a series of regression models and found that INS provides superior predictive power over single-brain measures. The INS-based Support Vector Regression model achieved an accuracy of 86.66% in predicting deception. This indicates that increased trust at closer social distances reduces vigilance and fosters relationship-oriented social information processing. As the first to identify INS as a neural marker for deception from the detector’s perspective, this work advances Interpersonal Deception Theory and offers a neuroscientific basis for credit risk management.

Significance Statement Using a sender–receiver paradigm and fNIRS hyperscanning, we investigated deception from the detector’s perspective across social distances and gain–loss contexts. Our findings reveal that interpersonal neural synchrony (INS) between the dorsolateral and orbitofrontal prefrontal cortices reliably predicts whether deception succeeds. We further analyzed the predictive power of INS at the trial level and found that deception susceptibility was first apparent in the early stages of verbal communication. These results suggest that deception is not solely shaped by individual vigilance but emerges from dynamic neural coupling during interaction. This study identifies INS as a neural signature of deception susceptibility and bridges behavioral models with neural computation, offering implications for deception detection in real-world social contexts.

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