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Starvation effect enables computing and memory functions in semiconductor-free fibres
Expansion of outer cortical CUX2 neurons requires adaptations for DNA repair
Abstract During mammalian evolution, excitatory neurons in upper cortical layer 2 and layer 3 (L2/3) have shown a disproportionate expansion compared with other layers 1–4 . Replicative expansion of cortical neural progenitors is associated with considerable oxidative DNA damage. Here we show that activating transcription factor 4 (ATF4) has roles as a critical regulator of the DNA damage response, directly activating components of double-stranded DNA repair, including CIRBP, UBA52 and EBF1. Notably, pan-cortical knockout ( Emx1-Cre; Atf4 fl/fl ) demonstrates that ATF4 is required specifically for the development of upper layer 2/3 neurons, marked by the expression of cut-like homeobox 2 protein, CUX2. ATF4 functions to repair DNA damage and attenuate cell death of embryonic radial glial progenitors in a p53-dependent manner. In particular, we show that cold inducible RNA-binding protein (CIRBP) is a transcriptional target of ATF4 that is required for normal phosphorylation of the key double-strand DNA repair factor ataxia telangiectasia mutated (ATM). These findings establish that ATF4 is an essential regulator of the DNA damage response. They further indicate that there are extraordinary requirements for DNA repair after replicative stress in CUX2 + neurons during mammalian brain development.
An autonomous single-actuator UAV with omnidirectional field of view, high agility, and collision resistance
C2orf74 orchestrates germ-Leydig crosstalk to inhibit white adipose tissue browning in male mice
Gene regulatory landscape dissected by single-cell four-omics sequencing
Disinfection of hospital sink drains enriches pseudomonadota and efflux pump-mediated antibiotic resistance in reestablished biofilms
Structural basis and physiological significance of non-canonical Gs coupling to the melatonin MT1 receptor
Abstract G protein-coupled receptors (GPCRs) transduce extracellular stimuli into intracellular signals by coupling to various heterotrimeric G proteins. However, the rules governing G protein preference remain largely elusive. MT 1 and MT 2 are prototypical G i/o -coupled GPCRs responding to melatonin, a hormone secreted in a circadian manner. We show here that MT 1 , but not MT 2 , couples also to G s proteins in vitro and activates the G s /cAMP pathway upon long-term melatonin exposure in vivo, mimicking physiological dawn conditions. We solve the cryo–electron microscopy structure of the melatonin-MT 1 -G s complex at 3.0 Å resolution, which reveals a distinct binding mode compared to the MT 1 –G i complex. The third intracellular loop of MT 1 emerges as a key stabilizer for G s coupling. This structure of a GPCR primarily coupling to G i , here in complex with G s , provides structural and functional insights into G protein selectivity and circadian switch of G protein coupling.
Over four minutes of pyruvate T1 using chemically and physically induced deceleration of relaxation
Abstract [1- 13 C]pyruvate is the most widely used probe for hyperpolarized metabolic magnetic resonance imaging, with profound applications in tumor and inflammation diagnosis as well as treatment monitoring. The most fundamental hurdle to broader application, however, remains the rapid relaxation of polarization and the associated signal loss. Here, we report a method to address this challenge. Studying the nuclear spin relaxation dispersion of [1- 13 C]pyruvate across magnetic fields from 8 μT to 9.4 T, as a function of additives, solvents, and preparation methods, allows us to achieve T 1 relaxation times of up to four minutes. Such a long T 1 could enable reliable quality control and nearly polarization loss-free transport, further boosting the power of hyperpolarized metabolic MRI. The power of the optimized protocol for T 1 elongation in vitro is showcased by more than doubling the sensitivity in a metabolic experiment.
Structure of giant kelp Photosystem I-FCP uncovers drivers of antenna evolution across the red lineage
Abstract Brown algae and other red-algae-derived organisms are major contributors to global CO 2 fixation via photosynthesis. To understand the photosynthetic function of brown algae, we obtained the structure of giant kelp Macrocystis pyrifera photosystem I (PSI) with a fucoxanthin-chlorophyll-protein (FCP) antenna and compared it to known structures from the red-algal lineage. We identified differences in M. pyrifera ’s antenna composition, architecture, and chlorophyll networks, as well as a pronounced variation in transmembrane hydrophobic thickness across the PSI-FCP supercomplex, with implications for photochemical function. Our work lays the foundation to understand kelp’s high photosynthetic productivity and reveals drivers of antenna conservation and diversification for the red lineage.
Facile induction of immune tolerance by an interleukin-2–TGFβ surrogate agonist
Abstract CD4 + regulatory T cells (T reg cells) are essential for immune tolerance 1 . Peripherally induced T reg cells (pT reg cells) complement thymic T reg cells by broadening T reg cell reactivity in response to a changing antigenic landscape 2 . Although both TGFβ and IL-2 synergistically promote functional pT reg cell development in vitro 3–6 , their combined roles in inducing pT reg cell generation in vivo have not been exploited for tolerizing immunotherapy. Here we designed an IL-2–TGFβ ‘surrogate’ co-agonist by creating a single-chain fusion protein between IL-2 and a low-affinity TGFβ mimic agonist derived from a helminth parasite 7 . This IL-2–TGFβ surrogate functions as an AND-gated co-agonist and enabled simultaneous cis -activation of IL-2–STAT5 and TGFβ–SMAD2/3 signalling specifically in T cells that express IL-2 receptors. The IL-2–TGFβ surrogate agonist robustly induced antigen-specific, functional and stable pT reg cells in vivo within peripheral lymphoid organs in mice immunized with ovalbumin (OVA) and myelin oligodendrocyte glycoprotein (MOG) 35–55 . The induced pT reg cells display an effector-like, actively expanding state with high RORγt expression, enabling efficient migration and suppression of intestinal inflammation. Treatment with this agonist effectively quelled immune activation in mouse models of allergen-induced allergic inflammation and self-antigen-driven autoimmune neuroinflammation, suggesting a strategy for the induction of antigen-specific pT reg cells in vivo to establish immune tolerance in inflammatory, allergic and autoimmune diseases.
Expanding canonical cortical cell type markers in the era of single-cell transcriptomics
Abstract Cell type markers have been instrumental to physiological and molecular investigation of the human brain and remain essential for annotating cell type clusters in single-cell expression data and for target validation studies. However, expression of canonical markers in the target cell type (which we termed as the expression ‘fidelity’) as well as expression in unrelated cell types (which we termed as the ‘background expression’) across cortical regions remains poorly characterized. Here, leveraging nearly 500,000 high-quality single-nucleus and single-cell profiles from 19 studies, we quantified marker fidelity, revealing substantial regional variability. We developed a statistical framework that aggregates annotated barcodes into pseudo-bulk profiles, applied rigorous performance metrics, and identified markers with high fidelity, low background, and consistent expression across regions. This approach extended the canonical marker set for six major brain cell types and yielded superior subtype-specific markers. The resulting marker lists, and a user-friendly analysis interface, provide a valuable resource for cell type annotation and validation in neuroscience research.
Mitochondria-derived vesicles with bioenergetic units from brown adipose tissue attenuate cardiac remodeling post-myocardial infarction
Abstract Post-myocardial infarction remodeling is a major cause of heart failure, with contributions from multiple organs. Brown adipose tissue protects against cardiovascular disease, but the mediators of brown adipose tissue-heart crosstalk and their roles in cardiac remodeling remain elusive. Here, we show that mitochondria-derived vesicles from brown adipose tissue transfer to cardiac macrophages and attenuate pathological remodeling via anti-inflammatory effects. Vesicles containing mitochondrial membranes, rather than mitochondrial matrix, mobilize from brown adipose tissue to the heart in response to stress. VPS35 translocation to mitochondria drives protein packaging into mitochondria-derived vesicles for secretion through extracellular vesicle trafficking machinery. Becn1 deficiency impairs VPS35 translocation, alters mitochondria-derived vesicle cargo, and abolishes brown adipose tissue-mediated cardioprotection. Proteomics identifies mitochondrial respiratory chain complex V as a hallmark of protective mitochondria-derived vesicles. These vesicles enhance reparative cytokine production and oxidative phosphorylation rewiring in macrophages. Purified mitochondria-derived vesicles markedly improve remodeling in male mice. Our study uncovers an interorgan transfer of bioenergetic units that contributes to tissue repair.
Comparison of ventilation with second-generation supraglottic airway devices in a prospective randomized cadaver study
Abstract Second-generation supraglottic airway devices (SADs) are widely used alternatives to endotracheal intubation in both anesthesia and emergency airway management. The newly developed LT®evo represents a redesigned version of the established Laryngeal Tube Suction Disposable (LTS-D). This study compared the ventilatory performance of the LT®evo with endotracheal intubation and three other second-generation SADs— LTS-D, Ambu® AuraGain™ and i-gel® Plus—using a controlled human cadaver model. In this prospective, randomized experiment, six thawed adult cadavers were sequentially ventilated via an endotracheal tube (ET) and four SADs under standardized mechanical ventilation (tidal volume 7 mL/kg, PEEP 5 cmH₂O, respiratory rate 10/min). Airway pressure and flow were continuously recorded (sampling rate 200 Hz) to determine inspiratory tidal volume, pressure, flow, and calculated resistance. Endotracheal intubation using fiberoptics was attempted via LT®evo , AuraGain™ and i-gel® Plus. Data were analyzed using Kruskal–Wallis tests with Holm-corrected post-hoc pairwise comparisons. From six human cadavers (60–85kg estimated body weight), 30 complete ventilation datasets were obtained. Initial fiberoptic control of SAD placement showed optimal positioning in 13 of 24 insertions. During ventilation cycles, inspiratory tidal volumes of the LT®evo (0.49 [0.46–0.52]) were similar to those of ET, AuraGain™ and LTS-D and superior to those of the i-gel® Plus (0.31 L [0.27–0.33], p < 0.001). Peak inspiratory pressure and inspiratory resistance were higher in ET when compared to LT®evo and all other SADs. Endotracheal intubation using fiberoptics was successful in all attempts via LT®evo , AuraGain™ and i-gel® Plus. In this controlled cadaver study, the newly designed LT®evo demonstrated ventilatory performance comparable to that of the LTS-D and the Ambu® AuraGain TM and was superior to the i-gel® Plus in delivering adequate tidal volumes. Additionally, LT®evo allowed for fiberoptic ET placement. Importantly, these results are specific to the cadaveric model and reflect technical variability in ventilation mechanics rather than clinical effectiveness. Clinical trial number German Clinical Trials Registry, DRKS00038309, on October 30 th , 2025.
Twenty-first century emergence of alpine fire in Central African mountains
Modeling of complex physical and biological problems using bi-univalent function calculus
A blockchain enabled IoT routing framework improving security and performance in smart cities
Pore-structure controls on absolute permeability of 1-mm digital sandstone subsamples under a fixed CT field of view
A global survey of systems biology-based predictions of gene-rare disease associations to enhance new diagnoses
Enhanced accuracy and adaptability: An ISSA-optimized MPC approach for AGV trajectory tracking
To enhance the tracking accuracy of AGVs, this paper proposes an online adaptive optimization strategy for MPC weight parameters based on the Improved Sparrow Search Algorithm (ISSA). Firstly, the kinematic and three-degree-of-freedom dynamic models of the AGV are established, and a trajectory tracking MPC controller based on an incremental model is designed. On this basis, the Tent chaotic mapping is introduced to initialize the population and enhance its diversity. A dynamic disturbance factor is incorporated into the position update of the discoverers, and a Cauchy mutation operator is introduced during the follower stage. These improvements effectively balance the algorithm’s global exploration and local exploitation capabilities, preventing premature convergence. This method uses a composite indicator of lateral and heading tracking errors as the fitness function to periodically optimize the MPC weight parameters online, thereby adapting to the control requirements of the AGV under different working conditions. Finally, validation through co-simulation using Gazebo and Rviz under the ROS framework, along with experiments on a forklift-type AGV, shows that the proposed method offers significant advantages in improving trajectory tracking accuracy, accelerating dynamic response, and enhancing adaptability to various working conditions. It thus provides a feasible solution for high-performance trajectory tracking control of AGVs.