Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase.

Recent studies identified cyclic GMP-AMP (cGAMP) as a metazoan second messenger triggering an interferon response. cGAMP is generated from GTP and ATP by cytoplasmic dsDNA sensor cGAMP synthase (cGAS). We combined structural, chemical, biochemical, and cellular assays to demonstrate that this second messenger contains G(2',5')pA and A(3',5')pG phosphodiester linkages, designated c[G(2',5')pA(3',5')p]. We show that, upon dsDNA binding, cGAS is activated through conformational transitions, resulting in formation of a catalytically competent and accessible nucleotide-binding pocket for generation of c[G(2',5')pA(3',5')p]. We demonstrate that cyclization occurs in a stepwise manner through initial generation of 5'-pppG(2',5')pA prior to cyclization to c[G(2',5')pA(3',5')p], with the latter positioned precisely in the catalytic pocket. Mutants of cGAS dsDNA-binding or catalytic pocket residues exhibit reduced or abrogated activity. Our studies have identified c[G(2',5')pA(3',5')p] as a founding member of a family of metazoan 2',5'-containing cyclic heterodinucleotide second messengers distinct from bacterial 3',5' cyclic dinucleotides.

TREM2: A new player in the tumor microenvironment.

TREM2 is a myeloid cell receptor that has been extensively described in the context of neuroinflammation and neurodegenerative diseases. Recently, TREM2 emerged as a crucial regulator of macrophage function in tumors. TREM2-deficiency or blockade provide protection and promote the response to anti-PD1 in different murine models. In human tumors, TREM2-expressing macrophages are present in numerous cohorts and tumor types and are generally associated with immunosuppression and poor prognosis. Here, we provide an overview of the impact of TREM2 in tumors considering current literature, with a focus on both murine models and human cancer.

Dysregulated CD200-CD200R signaling in early diabetes modulates microglia-mediated retinopathy.

Diabetic retinopathy (DR) is a neurovascular complication of diabetes. Recent investigations have suggested that early degeneration of the neuroretina may occur prior to the appearance of microvascular changes; however, the mechanisms underlying this neurodegeneration have been elusive. Microglia are the predominant resident immune cell in the retina and adopt dynamic roles in disease. Here, we show that ablation of retinal microglia ameliorates visual dysfunction and neurodegeneration in a type I diabetes mouse model. We also provide evidence of enhanced microglial contact and engulfment of amacrine cells, ultrastructural modifications, and transcriptome changes that drive inflammation and phagocytosis. We show that CD200-CD200R signaling between amacrine cells and microglia is dysregulated during early DR and that targeting CD200R can attenuate high glucose-induced inflammation and phagocytosis in cultured microglia. Last, we demonstrate that targeting CD200R in vivo can prevent visual dysfunction, microglia activation, and retinal inflammation in the diabetic mouse. These studies provide a molecular framework for the pivotal role that microglia play in early DR pathogenesis and identify a potential immunotherapeutic target for treating DR in patients.

Divergent signaling requirements of dSARM in injury-induced degeneration and developmental glial phagocytosis.

Elucidating signal transduction mechanisms of innate immune pathways is essential to defining how they elicit distinct cellular responses. Toll-like receptors (TLR) signal through their cytoplasmic TIR domains which bind other TIR domain-containing adaptors. dSARM/SARM1 is one such TIR domain adaptor best known for its role as the central axon degeneration trigger after injury. In degeneration, SARM1's domains have been assigned unique functions: the ARM domain is auto-inhibitory, SAM-SAM domain interactions mediate multimerization, and the TIR domain has intrinsic NAD+ hydrolase activity that precipitates axonal demise. Whether and how these distinct functions contribute to TLR signaling is unknown. Here we show divergent signaling requirements for dSARM in injury-induced axon degeneration and TLR-mediated developmental glial phagocytosis through analysis of new knock-in domain and point mutations. We demonstrate intragenic complementation between reciprocal pairs of domain mutants during development, providing evidence for separability of dSARM functional domains in TLR signaling. Surprisingly, dSARM's NAD+ hydrolase activity is strictly required for both degenerative and developmental signaling, demonstrating that TLR signal transduction requires dSARM's enzymatic activity. In contrast, while SAM domain-mediated dSARM multimerization is important for axon degeneration, it is dispensable for TLR signaling. Finally, dSARM functions in a linear genetic pathway with the MAP3K Ask1 during development but not in degenerating axons. Thus, we propose that dSARM exists in distinct signaling states in developmental and pathological contexts.

Creation of Room-Temperature Sub-100 nm Antiferromagnetic Skyrmions in an Antiferromagnet IrMn through Interfacial Exchange Coupling.

Antiferromagnetic (AFM) skyrmions are magnetic vortices composed of antiparallell-aligned neighboring spins. In stark contrast to conventional skyrmions based on ferromagnetic order, AFM skyrmions have vanished stray fields, higher response frequencies, and rectified translational motion driven by an external force. Therefore, AFM skyrmions promise highly efficient spintronics devices with high bit mobility and density. Nevertheless, the experimental realization of intrinsic AFM skyrmions remains elusive. Here, we show that AFM skyrmions can be nucleated via interfacial exchange coupling at the surface of a room-temperature AFM material, IrMn, exploiting the particular response from uncompensated moments to the thermal annealing and imprinting effects. Further systematic magnetic characterizations validate the existence of such an AFM order at the IrMn/CoFeB interfaces. Such AFM skyrmions have a typical size of 100 nm, which presents pronounced robustness against field and temperature. Our work opens new pathways for magnetic topological devices based on AFM skyrmions.

Single-crystalline van der Waals layered dielectric with high dielectric constant.

The scaling of silicon-based transistors at sub-ten-nanometre technology nodes faces challenges such as interface imperfection and gate current leakage for an ultrathin silicon channel1,2. For next-generation nanoelectronics, high-mobility two-dimensional (2D) layered semiconductors with an atomic thickness and dangling-bond-free surfaces are expected as channel materials to achieve smaller channel sizes, less interfacial scattering and more efficient gate-field penetration1,2. However, further progress towards 2D electronics is hindered by factors such as the lack of a high dielectric constant (κ) dielectric with an atomically flat and dangling-bond-free surface3,4. Here, we report a facile synthesis of a single-crystalline high-κ (κ of roughly 16.5) van der Waals layered dielectric Bi2SeO5. The centimetre-scale single crystal of Bi2SeO5 can be efficiently exfoliated to an atomically flat nanosheet as large as 250 × 200 µm2 and as thin as monolayer. With these Bi2SeO5 nanosheets as dielectric and encapsulation layers, 2D materials such as Bi2O2Se, MoS2 and graphene show improved electronic performances. For example, in 2D Bi2O2Se, the quantum Hall effect is observed and the carrier mobility reaches 470,000 cm2 V-1 s-1 at 1.8 K. Our finding expands the realm of dielectric and opens up a new possibility for lowering the gate voltage and power consumption in 2D electronics and integrated circuits.

Erratum: Current-Induced Creation of Topological Vortex Rings in a Magnetic Nanocylinder [Phys. Rev. Lett. 132, 126701 (2024)].

This corrects the article DOI: 10.1103/PhysRevLett.132.126701.

Current-Induced Creation of Topological Vortex Rings in a Magnetic Nanocylinder.

Vortex rings are ubiquitous topological structures in nature. In solid magnetic systems, their formation leads to intriguing physical phenomena and potential device applications. However, realizing these topological magnetic vortex rings and manipulating their topology on demand have still been challenging. Here, we theoretically show that topological vortex rings can be created by a current pulse in a chiral magnetic nanocylinder with a trench structure. The creation process involves the formation of a vortex ring street, i.e., a chain of magnetic vortex rings with an alternative linking manner. The created vortex rings can be bounded with monopole-antimonopole pairs and possess a rich and controllable linking topology (e.g., Hopf link and Solomon link), which is determined by the duration and amplitude of the current pulse. Our proposal paves the way for the realization and manipulation of diverse three-dimensional (3D) topological spin textures and could catalyze the development of 3D spintronic devices.

Robust fragment-based method of calculating hydrogen atom transfer activation barrier in complex molecules.

Dynamic processes driven by non-covalent interactions (NCI), such as conformational exchange, molecular binding, and solvation, can strongly influence the rate constants of reactions with low activation barriers, especially at low temperatures. Examples of this may include hydrogen-atom-transfer (HAT) reactions involved in the oxidative stress of an active pharmaceutical ingredient (API). Here, we develop an automated workflow to generate HAT transition-state (TS) geometries for complex and flexible APIs and then systematically evaluate the influences of NCI on the free activation energies, based on the multi-conformational transition-state theory (MC-TST) within the framework of a multi-step reaction path. The two APIs studied: fesoterodine and imipramine, display considerable conformational complexity and have multiple ways of forming hydrogen bonds with the abstracting radical-a hydroxymethyl peroxyl radical. Our results underscore the significance of considering conformational exchange and multiple activation pathways in activation calculations. We also show that structural elements and NCIs outside the reaction site minimally influence TS core geometry and covalent activation barrier, although they more strongly affect reactant binding and consequently the overall activation barrier. We further propose a robust and economical fragment-based method to obtain overall activation barriers, by combining the covalent activation barrier calculated for a small molecular fragment with the binding free energy calculated for the whole molecule.

Controllable and reusable seesaw circuit based on nicking endonucleases.

Seesaw circuits are essential for molecular computing and biosensing. However, a notable limitation of seesaw circuits lies in the irreversible depletion of components, precluding the attainment of system recovery and rendering nucleic acid circuits non-reusable. We developed a brand-new method for creating controllable and reusable seesaw circuits. By using the nicking endonucleases Nt.BbvCI and Nt.Alwi, we removed "functional components" while keeping the "skeletal components" for recurrent usage. T-inputs were introduced, increasing the signal-to-noise ratio of AND logic from 2.68 to 11.33 and demonstrating compatibility. We identified the logic switching feature and verified that it does not impair circuit performance. We also built intricate logic circuits, such as OR-AND gate, to demonstrate the versatility of our methodology. This controllable reusability extends the applications of nanotechnology and bioengineering, enhancing the practicality and efficiency of these circuits across various domains.

Evolution of Emergent Monopoles into Magnetic Skyrmion Strings.

Topological defects are fundamental concepts in physics, but little is known about the transition between distinct types across different dimensionalities. In topological magnetism, as in field theory, the transition between 1D strings and 0D monopoles is a key process whose observation has remained elusive. Here, we introduce a novel mechanism that allows for the controlled stabilization of emergent monopoles and show that magnetic skyrmion strings can be folded into monopoles. Conversely, they act as seeds out of which the entire string structure can unfold, containing its complete information. In chiral magnets, this process can be observed by resonant elastic X-ray scattering when the objects are in proximity to a polarized ferromagnet, whereby a pure monopole lattice is emerging on the surface. Our experimental proof of the reversible evolution from monopole to string sheds new light on topological defects and establishes the emergent monopole lattice as a new 3D topological phase.

Geometrically stabilized skyrmionic vortex in FeGe tetrahedral nanoparticles.

The concept of topology has dramatically expanded the research landscape of magnetism, leading to the discovery of numerous magnetic textures with intriguing topological properties. A magnetic skyrmion is an emergent topological magnetic texture with a string-like structure in three dimensions and a disk-like structure in one and two dimensions. Skyrmions in zero dimensions have remained elusive due to challenges from many competing orders. Here, by combining electron holography and micromagnetic simulations, we uncover the real-space magnetic configurations of a skyrmionic vortex structure confined in a B20-type FeGe tetrahedral nanoparticle. An isolated skyrmionic vortex forms at the ground state and this texture shows excellent robustness against temperature without applying a magnetic field. Our findings shed light on zero-dimensional geometrical confinement as a route to engineer and manipulate individual skyrmionic metastructures.

2-µm nonlinear post-compression for generating ∼100-MHz few-cycle laser pulses with watt-level average power.

We firstly report a high pulse repetition rate (101.4 MHz) nonlinear post-compression based on the normal dispersion fiber (NDF) operating in 2-µm wavelength region. With only one-stage NDF-based nonlinear pulse compressor, the 2-µm ultrafast laser pulses are compressed from ∼460 fs down to 70 fs, corresponding to ∼10.4 optical oscillation cycle. With two-stage nonlinear pulse compressor, the input ultrafast laser pulses are further compressed to 28.3 fs (∼4.3 optical oscillation cycle). In each case, the average power of the compressed 2-µm laser pulses exceeds 1 W, which is believed to be the highest average power never achieved at ∼100-MHz pulse repetition rate. The efficiencies of the one-stage and two-stage nonlinear pulse compressors are 64% and 47% respectively.

High-power, sub-100-fs, 1600-1700-nm all-fiber laser for deep multiphoton microscopy.

The 1600-1700-nm ultrafast fiber lasers attract great interests in the deep multiphoton microscopy, due to the reduced levels of the tissue scattering and absorption. Here, we report on the 86.7-MHz, 717-mW, 91.2-fs, all-fiber laser located in the spectral range from 1600 nm to 1700nm. The soliton self-frequency shift (SSFS) was introduced into the Er:Yb co-doped fiber amplifier (EYDFA) to generate the high-power, 1600-1700-nm Raman soliton. Detailed investigations of the nonlinear fiber amplification process were implemented in optimizing the generated Raman soliton pulses. The miniature multiphoton microscopy was further realized with this home-built laser source. The clearly imaging results can be achieved by collecting the generated harmonic signals from the mouse tail skin tissue with a penetration depth of ∼500 µm. The experimental results indicate the great potential in utilizing this 1600-1700-nm fiber laser in the deep multiphoton microscopy.

100-mJ, 100-W cryogenically cooled Yb:YLF laser.

We present a diode-pumped Yb:YLF laser system generating 100-mJ sub-ps pulses at a 1-kHz repetition rate (100 W average power) by chirped-pulse amplification. The laser consists of a cryogenically cooled 78 K, regenerative, eight-pass booster amplifier seeded by an all-fiber front end. The output pulses are compressed to 980 fs in a single-grating Treacy compressor with a throughput of 89%. The laser will be applied to multi-cycle THz generation and pumping of high average power parametric amplifiers.

Maximum Spreading Diameter of Bouncing Droplets at Ultralow Weber Numbers.

In the present work, we study the maximum spreading of bouncing droplets in the capillary regime at ultralow Weber numbers with a fixed static contact angle. In the ultralow Weber number region, experiments reveal that existing spreading laws are inapplicable because of gravity exclusion and change in deformation shape. We propose a theoretical scaling law based on energy conservation, modeling the deformed droplet as an ellipsoid with gravity effects. The proposed scaling law indicates the competition between gravity and inertia at ultralow Weber numbers and distinguishes their dominant regimes. By integrating higher-Weber-number regions, we reveal that viscosity is prominent in the previously assumed inviscid regime. Furthermore, we devise a phase diagram to clarify different impact regimes on the basis of energy analysis.

Porous organic polymers for Li-chemistry-based batteries: functionalities and characterization studies.

Porous organic polymers (POPs), a versatile class of materials that possess many tunable properties such as high chemical absorptivity and ionic conductivity, are emerging candidate electrode materials, permselective membranes, ionic conductors, interfacial stabilizers and functional precursors to synthesize advanced porous carbon. Based on their crystal structure features, the emerging POPs can be classified into two subclasses: amorphous POPs (hyper cross-linked polymers, polymers with intrinsic microporosity, conjugated microporous polymers, porous aromatic frameworks, etc.) and crystalline POPs (covalent organic frameworks, etc.). This tutorial review provides a brief introduction of different types of POPs in terms of their classification and functions for tackling the remaining challenges in various types of Li-chemistry-based batteries. In situ and ex situ characterization studies are also discussed to highlight their importance and applicability for the structural investigation of POPs to reveal the underlying mechanism of POPs over the course of the electrochemical process. Although some revolutionary advances have been achieved, the development of POPs in Li-chemistry-based batteries is still in its infancy. Perspectives regarding future application and mechanistic insights of POPs in battery studies are outlined at the end.

A Route Planning Method for UAV Swarm Inspection of Roads Fusing Distributed Droneport Site Selection.

Current methods that use Unmanned Aerial Vehicle (UAV) swarms to inspect roads still have many limitations in practical applications, such as the lack of or difficulty in the route planning, the unbalanced utilization rate of the UAV swarm and the difficulty of the site selection for the distributed droneports. To solve the limitations, firstly, we construct the inspection map and remove the redundant information irrelevant to the road inspection. Secondly, we formulate both the route planning problem and the droneport site selection problem in a unified multi-objective optimization model. Thirdly, we redesign the encoding strategy, the updating rules and the decoding strategy of the particle swarm optimization method to effectively solve both the route planning problem and the droneport site selection problem. Finally, we introduce the comprehensive evaluation indicators to verify the effectiveness of the route planning and the droneport site selection. The experimental results show that (1) with the proposed method, the overlapped part of the optimized inspection routes is less than 7% of the total mileage, and the balanced utilization rate of the UAVs is above 75%; (2) the reuse rate of the distributed droneports is significantly improved after optimization; and (3) the proposed method outperforms the ant colony optimization (ACO) method in all evaluation indicators. To this end, the proposed method can effectively plan the inspection routes, balance the utilization of the UAVs and select the sites for the distributed droneports, which has great significance for a fully autonomous UAV swarm inspection system for road inspection.

Ubiquitous Topological States of Phonons in Solids: Silicon as a Model Material.

Research on topological physics of phonons has attracted enormous interest but demands appropriate model materials. Our ab initio calculations identify silicon as an ideal candidate material containing extraordinarily rich topological phonon states. In silicon, we identify various topological nodal lines characterized by quantized Berry phase π, which gives drumhead surface states observable from any surface orientations. Remarkably, a novel type of topological nexus phonon is discovered which is featured by double Fermi-arc-like surface states but requires neither inversion nor time-reversal symmetry breaking. Versatile topological states can be created from the nexus phonons, such as Hopf nodal links by strain. Furthermore, we generalize the symmetry analysis to other centrosymmetric systems and find numerous candidate materials, demonstrating the ubiquitous existence of topological phonons in solids. These findings open up new opportunities for studying topological phonons in realistic materials and their influence on surface physics.

Axially Bound Magnetic Skyrmions: Glueing Topological Strings Across an Interface.

A major challenge in topological magnetism lies in the three-dimensional (3D) exploration of their magnetic textures. A recent focus has been the question of how 2D skyrmion sheets vertically stack to form distinct types of 3D topological strings. Being able to manipulate the vertical coupling should therefore provide a route to the engineering of topological states. Here, we present a new type of axially bound magnetic skyrmion string state in which the strings in two distinct materials are glued together across their interface. With quasi-tomographic resonant elastic X-ray scattering, the 3D skyrmion profiles before and after their binding across the interface were unambiguously determined and compared. Their attractive binding is accompanied by repulsive twisting; i.e., the coupled skyrmions mutually affect each other via a compensating twisting. This state exists in chiral magnet-magnetic thin film heterostructures, providing a new arena for the engineering of 3D topological phases.