Spinal projecting neurons in rostral ventromedial medulla co-regulate motor and sympathetic tone.

Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord. Fiber-photometry recording indicated that the activities of rVMM SPNs correlate with different levels of muscle and sympathetic tone during distinct arousal states. Inhibiting rVMM excitatory SPNs reduced basal muscle and sympathetic tone, impairing locomotion initiation and high-speed performance. In contrast, silencing the inhibitory population abolished muscle atonia and sympathetic hypoactivity during rapid eye movement (REM) sleep. Together, these results identify rVMM SPNs as descending spinal projecting pathways controlling the tone of both the somatomotor and sympathetic systems.

Exploration of Molecular Nanoparticles as Soft Structural Materials and Their Structure-Property Relationship.

The search for alternative chemical systems other than polymers with chain topologies for soft structural materials raises general interests in fundamental materials and chemical sciences. It is also appealing from an engineering perspective for the urgent need to resolve the typical trade-offs of polymer systems. Herein, a subnanometer molecular cluster, polyhedral oligomeric silsesquioxanes, is assembled into molecular nanoparticles (MNPs) with star topology. Broadly tunable viscoelasticity can be realized by fine-tuning the MNPs' deformability. Being analogous to polymeric systems, the hierarchical structural relaxation dynamics can be observed, and their relaxation time and temperature dependence are dominated by the linker flexibilities. This not only provides microscopic understanding on MNP's unique viscoelasticity but also offers enormous opportunities for modulating their mechanical properties via linker engineering. Our work proves the possibility of applying structural units with particle topologies for the design of soft structural materials.

Self-assembled soft alloy with Frank-Kasper phases beyond metals.

Soft building blocks, such as micelles, cells or soap bubbles, tend to adopt near-spherical geometry when densely packed together. As a result, their packing structures do not extend beyond those discovered in metallic glasses, quasicrystals and crystals. Here we report the emergence of two Frank-Kasper phases from the self-assembly of five-fold symmetric molecular pentagons. The µ phase, an important intermediate in superalloys, is indexed in soft matter, whereas the ϕ phase exhibits a structure distinct from known Frank-Kasper phases in metallic systems. We find a broad size and shape distribution of self-assembled mesoatoms formed by molecular pentagons while approaching equilibrium that contribute to the unique packing structures. This work provides insight into the manipulation of soft building blocks that deviate from the typical spherical geometry and opens avenues for the fabrication of 'soft alloy' structures that were previously unattainable in metal alloys.

Hierarchically Structured Nanocomposites via Mixed-Graft Block Copolymer Templating: Achieving Controlled Nanostructure and Functionality.

Integrating inorganic and polymerized organic functionalities to create composite materials presents an efficient strategy for the discovery and fabrication of multifunctional materials. The characteristics of these composites go beyond a simple sum of individual component properties; they are profoundly influenced by the spatial arrangement of these components and the resulting homo-/hetero-interactions. In this work, we develop a facile and highly adaptable approach for crafting nanostructured polymer-inorganic composites, leveraging hierarchically assembling mixed-graft block copolymers (mGBCPs) as templates. These mGBCPs, composed of diverse polymeric side chains that are covalently tethered with a defined sequence to a linear backbone polymer, self-assemble into ordered hierarchical structures with independently tuned nano- and mesoscale lattice features. Through the coassembly of mGBCPs with diversely sized inorganic fillers such as metal ions (ca. 0.1 nm), metal oxide clusters (0.5-2 nm), and metallic nanoparticles (>2 nm), we create three-dimensional filler arrays with controlled interfiller separation and arrangement. Multiple types of inorganic fillers are simultaneously integrated into the mGBCP matrix by introducing orthogonal interactions between distinct fillers and mGBCP side chains. This results in nanocomposites where each type of filler is selectively segregated into specific nanodomains with matrix-defined orientations. The developed coassembly strategy offers a versatile and scalable pathway for hierarchically structured nanocomposites, unlocking new possibilities for advanced materials in the fields of optoelectronics, sensing, and catalysis.

A Thiol-Michael Approach Towards Versatile Functionalized Cyclic Titanium-Oxo Clusters.

In expanding our research activities of superlattice engineering, designing new giant molecules is the necessary first step. One attempt is to use inorganic transition metal clusters as building blocks. Efficient functionalization of chemically precise transition metal clusters, however, remains a great challenge to material scientists. Herein, we report an efficient thiol-Michael addition approach for the modifications of cyclic titanium-oxo cluster (CTOC). Several advantages, including high efficiency, mild reaction condition, capability of complete addition, high atom economy, as well as high functional group tolerance were demonstrated. This approach can afford high yields of fully functionalized CTOCs, which provides a powerful platform for achieving versatile functionalization of precise transition metal clusters and further applications.

Physical exercise modulates the microglial complement pathway in mice to relieve cortical circuitry deficits induced by mutant human TDP-43.

The aggregation of TAR DNA binding protein 43 kDa (TDP-43) is related to different neurodegenerative diseases, which leads to microglial activation and neuronal loss. The molecular mechanism driving neuronal death by reactive microglia, however, has not been completely resolved. In this study, we generated a mouse model by overexpressing mutant human TDP-43 (M337V) in the primary motor cortex, leading to prominent motor-learning deficits. In vivo 2-photon imaging shows an active approach of microglia toward parvalbumin interneurons, resulting in disrupted cortical excitatory-inhibitory balance. Proteomics studies suggest that activation of the complement pathway induces microglial activity. To develop an early interventional strategy, treadmill exercise successfully prevents the deterioration of motor dysfunction under enhanced adipocytic release of clusterin to block the complement pathway. These results demonstrate a previously unrecognized pathway by which TDP-43 induces cortical deficits and provide additional insights for the mechanistic explanation of exercise training in disease intervention.

A gut-brain axis mediates sodium appetite via gastrointestinal peptide regulation on a medulla-hypothalamic circuit.

Salt homeostasis is orchestrated by both neural circuits and peripheral endocrine factors. The colon is one of the primary sites for electrolyte absorption, while its potential role in modulating sodium intake remains unclear. Here, we revealed that a gastrointestinal hormone, secretin, is released from colon endocrine cells under body sodium deficiency and is indispensable for inducing salt appetite. As the neural substrate, circulating secretin activates specific receptors in the nucleus of the solitary tracts, which further activates the downstream paraventricular nucleus of the hypothalamus, resulting in enhanced sodium intake. These results demonstrated a previously unrecognized gut-brain pathway for the timely regulation of sodium homeostasis.

Secretin receptor deletion in the subfornical organ attenuates the activation of excitatory neurons under dehydration.

In mammals, thirst is strongly influenced by the subfornical organ (SFO), a forebrain structure that integrates circulating signals including osmotic pressure and sodium contents. Secretin (SCT), a classical gastrointestinal hormone, has been implicated as a humoral factor regulating body-fluid homeostasis. However, the neural mechanism of secretin in the central nervous system in managing thirst remains unclear. In this study, we report that the local ablation of SCT receptor (SCTR) in the SFO reduces water but not salt intake in dehydrated mice and this effect could not be rescued by exogenous SCT administration. Electrophysiology with single-cell RT-PCR indicates that SCT elicits inward currents in the SFO neuronal nitric oxide synthase (SFOnNOS) neurons via SCTR in the presence of glutamate receptor antagonists. We further show that the SCTR in the SFO permits the activation of SFOnNOS neurons under distinct thirst types. Projection-specific gene deletion of SCTR in SFO to the median preoptic nucleus (MnPO) pathway also reduces water intake in dehydrated animals. SCT signaling thus plays an indispensable role in driving thirst. These data not only expand the functional boundaries of SCTR but also provide insights into the central mechanisms of homeostatic regulation.

Celsr3 Inactivation in the Brainstem Impairs Rubrospinal Tract Development and Mouse Behaviors in Motor Coordination and Mechanic-Induced Response.

Inactivation of Celsr3 in the forebrain results in defects of longitudinal axonal tracts such as the corticospinal tract. In this study, we inactivated Celsr3 in the brainstem using En1-Cre mice (Celsr3 cKO) and analyzed axonal and behavioral phenotypes. Celsr3 cKO animals showed an 83% reduction of rubrospinal axons and 30% decrease of corticospinal axons in spinal segments, associated with increased branching of dopaminergic fibers in the ventral horn. Decreases of spinal motoneurons, neuromuscular junctions, and electromyographic signal amplitude of the biceps were also found in mutant animals. Mutant mice had impaired motor coordination and defective response to heavy mechanical stimulation, but no disability in walking and food pellet handling. Transsynaptic tracing demonstrated that rubrospinal axons synapse on spinal neurons in the deep layer of the dorsal horn, and mechanical stimulation of hindpaws induced strong calcium signal of red nuclei in control mice, which was less prominent in mutant mice. In conclusion, Celsr3 regulates development of spinal descending axons and the motor network in cell and non-cell autonomous manners, and the maturation of the rubrospinal system is required for motor coordination and response to mechanical stimulation.

Unimolecular Nanoparticles toward More Precise Regulations of Self-Assembled Superlattices in Soft Matter.

The hierarchical self-assembly process opens up great potential for the construction of nanostructural superlattices. Precise regulation of self-assembled superlattices, however, remains a challenge. Even when the primary molecules are precise, the supramolecular motifs (or secondary building blocks) can vary dramatically. In the present work, we propose the concept of unimolecular nanoparticles (UMNPs). The UMNPs act as the supramolecular motif and directly pack into the superlattices. A highly branched giant molecule is presented. We systematically explore its conformations and the superlattice of this giant molecule. Moreover, intriguing complex phases are discovered when blending this UMNP with other conventional giant molecules. These binary mixtures provide direct evidence to support our previously proposed self-sorting process in the self-assembly of "soft alloys". The concept of UMNPs offers a unique approach toward more precise regulation of self-assembled superlattices in soft matter.

The oldest fossil record of Pseudopsinae from the Lower Cretaceous Yixian Formation of northeastern China (Coleoptera: Staphylinidae: Pseudopsinae).

The Cretaceous witnessed a radiation of rove beetles (Staphylinidae), the most species-rich beetle family. Although most staphylinid subfamilies have been documented from Cretaceous strata over the world, there has been no fossil record of the subfamily Pseudopsinae until a recently reported fossil from the 99-Ma-old Myanmar amber. Here we describe a new compression fossil from the Lower Cretaceous Yixian Formation of northeastern China. It is described as Cretaceonanobius fossilis. gen. et sp. nov. and assigned to the extant subfamily Pseudopsinae, based on the well-preserved carinae on the pronotum, a carina on ventrites II and III, and distinctly separated mesocoxae. The discovery of Cretaceonanobius fossilis gen. et sp. nov. backdates the earliest fossils record of Pseudopsinae to 125 Ma in the Northern Hemisphere and sheds new lights on the evolution history and paleobiogeography of this subfamily.

Soft Alloys Constructed with Distinct Mesoatoms via Self-Sorting Assembly of Giant Shape Amphiphiles.

The packing structures of spherical motifs affect the properties of resultant condensed materials such as in metal alloys. Inspired by the classic metallurgy, developing complex alloy-like packing phases in soft matter (also called "soft alloys") is promising for the next-generation superlattice engineering. Nevertheless, the formation of many alloy-like phases in single-component soft matter is usually thermodynamically unfavourable and technically challenging. Here, we utilize a novel self-sorting assembly approach to tackle this challenge in binary blends of soft matter. Two types of giant shape amphiphiles self-sort to form their discrete spherical motifs, which further simultaneously pack into alloy-like phases. Three unconventional spherical packing phases have been observed in these binary systems, including MgZn2 , NaZn13 , and CaCu5 phases. It's the first time that the CaCu5 phase is experimentally observed in soft matter. This work demonstrates a general approach to constructing unconventional spherical packing phases and other complex superlattices in soft matter.

Expanding quasiperiodicity in soft matter: Supramolecular decagonal quasicrystals by binary giant molecule blends.

The quasiperiodic structures in metal alloys have been known to depend on the existence of icosahedral order in the melt. Among different phases observed in intermetallics, decagonal quasicrystal (DQC) structures have been identified in many glass-forming alloys yet remain inaccessible in bulk-state condensed soft matters. Via annealing the mixture of two giant molecules, the binary system assemblies into an axial DQC superlattice, which is identified comprehensively with meso-atomic accuracy. Analysis indicates that the DQC superlattice is composed of mesoatoms with an unusually broad volume distribution. The interplays of submesoatomic (molecular) and mesoatomic (supramolecular) local packings are found to play a crucial role in not only the formation of the metastable DQC superlattice but also its transition to dodecagonal quasicrystal and Frank-Kasper σ superlattices.

Superlattice Engineering with Chemically Precise Molecular Building Blocks.

Correlating nanoscale building blocks with mesoscale superlattices, mimicking metal alloys, a rational engineering strategy becomes critical to generate designed periodicity with emergent properties. For molecule-based superlattices, nevertheless, nonrigid molecular features and multistep self-assembly make the molecule-to-superlattice correlation less straightforward. In addition, single component systems possess intrinsically limited volume asymmetry of self-assembled spherical motifs (also known as "mesoatoms"), further hampering novel superlattices' emergence. In the current work, we demonstrate that properly designed molecular systems could generate a spectrum of unconventional superlattices. Four categories of giant molecules are presented. We systematically explore the lattice-forming principles in unary and binary systems, unveiling how molecular stoichiometry, topology, and size differences impact the mesoatoms and further toward their superlattices. The presence of novel superlattices helps to correlate with Frank-Kasper phases previously discovered in soft matter. We envision the present work offers new insights about how complex superlattices could be rationally fabricated by scalable-preparation and easy-to-process materials.

Ordered Mesoporous Silica Pyrolyzed from Single-Source Self-Assembled Organic-Inorganic Giant Surfactants.

We report the preparation of hexagonal mesoporous silica from single-source giant surfactants constructed via dihydroxyl-functionlized polyhedral oligomeric silsesquioxane (DPOSS) heads and a polystyrene (PS) tail. After thermal annealing, the obtained well-ordered hexagonal hybrid was pyrolyzed to afford well-ordered mesoporous silica. A high porosity (e.g., 581 m2/g) and a uniform and narrow pore size distribution (e.g., 3.3 nm) were achieved. Mesoporous silica in diverse shapes and morphologies were achieved by processing the precursor. When the PS tail length was increased, the pore size expanded accordingly. Moreover, such pyrolyzed, ordered mesoporous silica can help to increase both efficiency and stability of nanocatalysts.

Crystallization Induced Self-Assembly: A Strategy to Achieve Ultra-Small Domain Sizes.

Achieving self-assembled nanostructures with ultra-small feature sizes (e. g., below 5 nm) is an important prerequisite for the development of block copolymer lithography. In this work, the preparation and self-assembly of a series of giant molecules composed of vinyl polyhedral oligomeric silsesquioxane (VPOSS) tethered with monodispersed oligo(L-lactide) chains are presented. Small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) results demonstrate that ultra-small domain sizes (down to 3 nm) of phase separated lamellar morphology are achieved in bulk, driven by the strong tendency and fast kinetics for crystallization of VPOSS moieties. Moreover, upon gamma ray radiation, VPOSS cages in the lamellar structure can be crosslinked via polymerization of the vinyl groups. After pyrolysis at high temperature, ultra-thin two-dimensional nano-silica sheets can be obtained.

Unexpected Elasticity in Assemblies of Glassy Supra-Nanoparticle Clusters.

Granular materials, composed of densely packed particles, are known to possess unique mechanical properties that are highly dependent on the surface structure of the particles. A microscopic understanding of the structure-property relationship in these systems remains unclear. Here, supra-nanoparticle clusters (SNPCs) with precise structures are developed as model systems to elucidate the unexpected elastic behaviors. SNPCs are prepared by coordination-driven assembly of polyhedral oligomeric silsesquioxane (POSS) with metal-organic polyhedron (MOP). Due to the disparity in sizes, the POSS-MOP assemblies, like their classic nanoparticles counterparts, ordering is suppressed, and the POSS-MOP mixtures will vitrify or jam as a function of decreasing temperature. An unexpected elasticity is observed for the SNPC assemblies with a high modulus that is maintained at temperatures far beyond the glass transition temperature. From studies on the dynamics of the hierarchical structures of SNPCs and molecular dynamic simulation, the elasticity has its origins in the interpenetration of POSS-ended arms. The physical molecular interpenetration and inter-locking phenomenon favors the convenient solution or pressing processing of the novel cluster-based elastomers.

Geometry-Directed Self-Assembly of Polymeric Molecular Frameworks.

Despite the significant advances in creating assembled structures from polymers, engineering the assembly of polymeric materials into framework structures remains an outstanding challenge. In this work, we present a facile strategy to construct polymeric molecular frameworks through the assembly of T-shape polymer-rod-sphere amphiphiles in the bulk state. Various frameworks are yielded as a result of delicate interplays among three components of the T-shape amphiphiles. The internal structure of frameworks was revealed by combining experimental investigations and computational simulations. The frameworks display good solution-processability, thermal stability, and uniform pore-forming capability, which endow the resultant frameworks with great potential in scalable fabrications.

First fossil pseudopsine rove beetle from mid-Cretaceous Burmese amber (Coleoptera: Staphylinidae: Pseudopsinae).

Pseudopsinae represented by four genera with just over 50 species in the Recent fauna represent one of the smallest subfamilies of the megadiverse family Staphylinidae. Here we describe the first fossil member of the subfamily Pseudopsinae. Cretopseudopsis maweii gen. et sp. nov. preserved in mid-Cretaceous Burmese amber (ca. 99 Ma) is distinguished from extant pseudopsine genera by head not carinate, apical maxillary palpomere only slightly narrower than penultimate segment, subocular carinae absent, temples short, pronotal lateral margin smoothly rounded, and mesocoxae separated by an elongate process of the mesoventrite. Our discovery of Cretopseudopsis gen. et sp. nov. provides evidence that the subfamily Pseudopsinae originated by the Albian-Cenomanian and suggests a Gondwanan distribution of the group in the Cretaceous.

Molecular Patchy Clusters with Controllable Symmetry Breaking for Structural Engineering.

Anisotropic patchy particles with molecular precision are exquisite building blocks for constructing diverse meso-structures of high complexity. In this research, a library of molecular patchy clusters consisting of a collection of functional polyhedral oligomeric silsesquioxane cages with exact regio-configuration and composition were prepared through a robust and modular approach. By meticulously tuning the composition, molecular symmetry, and other parameters, these patchy clusters could assemble into diverse nanostructures, including unconventional complex spherical phases (i.e., Frank-Kasper σ phase and dodecagonal quasicrystalline phase). As the size of the hydrophilic patch expands, a transition sequence from disorder to hexagonally packed cylinders and then to double gyroids was recorded, corresponding to a progressive decrease of interfacial curvature. On the other hand, regioisomers with the same composition but different regio-configuration adopt similar molecular packing but varied phase stability, as a result of the local self-sorting process to alleviate excess unfavorable interfacial contact. These precisely defined molecular patchy clusters provide a model system for a general understanding of the hierarchical structure formation and evolution based on anisotropic spherical building blocks at the nanoscale.