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Werner et al. present the results of the 201 Trial, a 12-week randomized, double-blind placebo-controlled phase 2a study of risvodetinib, in patients with early untreated Parkinson’s disease. Risvodetinib was found to be safe and well tolerated.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Primary cutaneous B-cell lymphoma encompass clinically heterogeneous entities, including indolent and aggressive subtypes. Here, the authors show that the two indolent subtypes exhibit a persistent germinal centre reaction and thus may be driven by (a yet unknown) antigen.

In this study, authors employ fragment-based lead discovery to identify WRN inhibitors. The fragment hits reveal an additional allosteric pocket and uncover a previously uncharacterized structural conformation of the WRN helicase domain with unique orientations of the ATPase domains

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.

The relative contribution of lipid catabolism on fasting-induced longevity was unknown. Authors showed lifespan extension from fasting depend on silencing lipid catabolism upon nutrient replenishment through phosphorylation of NHR-49 by KIN-19.

In this study, Kennedy et al. combine crystallography, biophysical measurements and biochemical assays to define a structural cycle for Werner syndrome helicase (WRN) and reveal how nucleotide binding and ssDNA engagement lead to conformational transitions.

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.

T cells contribute to protection and pathogenesis in tuberculosis. Here the authors sequence T cell receptor repertoires in human skin biopsies from the site of the tuberculin skin test and show enrichment of clonotypes reactive to Mycobacterium tuberculosis using a computational pipeline metaclonotypist to identify distinct TCRs predicted to share peptide-MHC reactivity across participants, as an approach to explore T cell correlates of tuberculosis disease-risk stratification and vaccine efficacy.

Here the authors show that endogenous or therapeutically delivered GDF-15 activates brainstem neurons that trigger splenic β-adrenergic signaling. This, in turn, suppresses autoreactive T cells and reduces neuroinflammation, identifying a possible target for multiple sclerosis treatment.

Borsa et al. show that asymmetric T cell division after activation requires autophagy to promote mitochondrial turnover, with T cells inheriting older mitochondria showing decreased degradation, reduced memory potential and altered metabolism.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Family history of premature coronary artery disease is a well-recognized, but under-recorded, risk factor that captures the complex interplay among shared genetic, environmental and lifestyle factors within families. Here, Lan et al. review the mechanisms of inherited risk, discuss the current limitations of family history in risk stratification models and outline future directions for precision care in families with a history of premature coronary artery disease.

RNA polymerase III transcribes essential non-coding RNAs, but many aspects of this biology remain unclear. Here, the authors develop DRAP3R, a nanopore sequencing method that captures Pol III transcripts and RNA modifications, revealing new RNAs and dynamic modification patterns.

Through next-generation spectral analysis, scientists have uncovered an evolutionary path for Wolf–Rayet stars in metal-poor environments. Characterized by hard ionizing radiation, these stars challenge current assumptions about massive star evolution.

Levels of the metabolic coenzyme NAD⁺ decline during aging, which is linked to many age-related diseases. Zhang et al. review recent clinical and translational evidence testing NAD⁺ supplementation in age-related diseases, highlighting therapeutic challenges and opportunities.

Antimony selenide is a promising photovoltaic material, but the presence of point defects degrades performance. Here, the authors use positron annihilation spectroscopy combined with theory to detect and identify vacancy-type point defects.

IL-17A, a cytokine important for tissue repair, can impair healing when increased, contributing to keratinocyte dysfunction in type 2 diabetic wounds. Here, the authors show that IL-17A drives this dysfunction via JMJD3-mediated epigenetic changes, and that blocking this pathway improves wound healing.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

The prevalent fungal pathogen, Candida albicans, and the emerging multidrug-resistant superfungus, Candida auris, share the same initial cell wall architecture but remodel it differently in response to echinocandin-induced antifungal stress.

Cavity-mediated interactions lead to collective effects and ordering in ultracold atomic systems. Here, the authors demonstrate the interplay of different ordered states of ultracold Fermi gases in a cavity, resulting from an intriguing coexistence of photon coupling with both atoms and atom-pairs.

Metabolic and proteomic profiles derived from fossilized skeletal remains of animals enable inferences regarding physiological health and disease as well as diet to provide reconstructions of ancient soil, vegetation and palaeoclimate characteristics.

Clinical diagnostic criteria for Parkinson disease (PD) have limitations, but no validated biomarker-based diagnostic framework currently exists. In this Review, Tolosa et al. examine progress towards biomarker-based diagnosis of PD, focusing on α-synuclein seed amplification assays alongside molecular, imaging and genetic markers.

A memristive blinking neuron—relying on atomic-scale filamentary dynamics for resistive switching and emitting photon pulses on integrating a critical number of incoming electrical spikes—can be used to build photonically linked three-dimensional spiking neural networks.

Oxidative catalytic depolymerization of polystyrene (PS) can produce benzoic acid, but the annual consumption of benzoic acid is ~40 times lower than PS, so benzoic acid should be converted to higher-volume chemicals for the process to be viable. Here, the authors report a hybrid chemical and biological process that uses PS as feedstock for production of adipic acid, a high-volume co-monomer for nylon 6,6, via benzoic acid.

The detection of the auroral footprint of Jupiter’s moon Callisto is challenging, but a shift in Jupiter’s bright main auroral oval could provide an opportunity for potential detections. Here, the authors show observation of the ultraviolet footprint of Callisto using Juno spacecraft data, benefiting from such opportunity.

Though integrating functional organic materials with semiconductor nanostructures is attractive for 3D chip processing, realizing these hybrids remains a challenge. Here, the authors report an oxidative chemical vapor deposition-based process for designing novel 3D hybrid optoelectronic structures.

Contrary to common chemical intuition, cation-π interactions can persist in polar, aqueous reaction solutions, rather than in dry non-coordinative solvent systems. Here, the authors highlight how alkali ion-π interactions impart distinctive structure-influencing supramolecular forces that can be exploited in the preparation of nanoscopic metal-organic capsules.

The authors identify causality-enriched CpGs linked to aging using Mendelian randomization. They develop new epigenetic clocks, DamAge and AdaptAge, that more reliably track age-related changes, offering insights into aging mechanisms and interventions.