Longitudinal in vivo Ca2+ imaging reveals dynamic activity changes of diseased retinal ganglion cells at the single-cell level.

Retinal ganglion cells (RGCs) are heterogeneous projection neurons that convey distinct visual features from the retina to brain. Here, we present a high-throughput in vivo RGC activity assay in response to light stimulation using noninvasive Ca2+ imaging of thousands of RGCs simultaneously in living mice. Population and single-cell analyses of longitudinal RGC Ca2+ imaging reveal distinct functional responses of RGCs and unprecedented individual RGC activity conversions during traumatic and glaucomatous degeneration. This study establishes a foundation for future in vivo RGC function classifications and longitudinal activity evaluations using more advanced imaging techniques and visual stimuli under normal, disease, and neural repair conditions. These analyses can be performed at both the population and single-cell levels using temporal and spatial information, which will be invaluable for understanding RGC pathophysiology and identifying functional biomarkers for diverse optic neuropathies.

Stabilizing and Activating Active Sites: 1T-MoS2 Supported Pd Single Atoms for Efficient Hydrogen Evolution Reaction.

Metallic 1T-MoS2 with high intrinsic electronic conductivity performs Pt-like catalytic activity for hydrogen evolution reaction (HER). However, obtaining pure 1T-MoS2 is challenging due to its high formation energy and metastable properties. Herein, an in situ SO4 2--anchoring strategy is reported to synthesize a thin layer of 1T-MoS2 loaded on commercial carbon. Single Pd atoms, constituting a substantial loading of 7.2 wt%, are then immobilized on the 1T-phase MoS2 via Pd─S bonds to modulate the electronic structure and ensure a stable active phase. The resulting Pd1/1T-MoS2/C catalyst exhibits superior HER performance, featuring a low overpotential of 53 mV at the current density of 10 mA cm-2, a small Tafel slope of 37 mV dec-1, and minimal charge transfer resistance in alkaline electrolyte. Moreover, the catalyst also demonstrates efficacy in acid and neutral electrolytes. Atomic structural characterization and theoretical calculations reveal that the high activity of Pd1/1T-MoS2/C is attributed to the near-zero hydrogen adsorption energy of the activated sulfur sites on the two adjacent shells of atomic Pd.

Promoting Electrocatalytic CO2 Reduction to CH4 by Copper Porphyrin with Donor-Acceptor Structures.

Molecular catalysts have been receiving increasingly attention in the electrochemical CO2 reduction reaction (CO2 RR) with attractive features such as precise catalytic sites and tunable ligands. However, the insufficient activity and low selectivity of deep reduction products restrain the utilization of molecular catalysts in CO2 RR. Herein, a donor-acceptor modified Cu porphyrin (CuTAPP) is developed, in which amino groups are linked to donate electrons toward the central CuN4 site to enhance the CO2 RR activity. The CuTAPP catalyst exhibited an excellent CO2 -to-CH4 electroreduction performance, including a high CH4 partial current density of 290.5 mA cm-2 and a corresponding Faradaic efficiency of 54.8% at -1.63 V versus reversible hydrogen electrode in flow cells. Density functional theory calculations indicated that CuTAPP presented a much lower energy gap in the pathway of producing *CHO than Cu porphyrin without amino group modification. This work suggests a useful strategy of introducing designed donor-acceptor structures into molecular catalysts for enhancing electrochemical CO2 conversion toward deep reduction products.

NMNAT2 is downregulated in glaucomatous RGCs, and RGC-specific gene therapy rescues neurodegeneration and visual function.

The lack of neuroprotective treatments for retinal ganglion cells (RGCs) and optic nerve (ON) is a central challenge for glaucoma management. Emerging evidence suggests that redox factor NAD+ decline is a hallmark of aging and neurodegenerative diseases. Supplementation with NAD+ precursors and overexpression of NMNAT1, the key enzyme in the NAD+ biosynthetic process, have significant neuroprotective effects. We first profile the translatomes of RGCs in naive mice and mice with silicone oil-induced ocular hypertension (SOHU)/glaucoma by RiboTag mRNA sequencing. Intriguingly, only NMNAT2, but not NMNAT1 or NMNAT3, is significantly decreased in SOHU glaucomatous RGCs, which we confirm by in situ hybridization. We next demonstrate that AAV2 intravitreal injection-mediated overexpression of long half-life NMNAT2 mutant driven by RGC-specific mouse γ-synuclein (mSncg) promoter restores decreased NAD+ levels in glaucomatous RGCs and ONs. Moreover, this RGC-specific gene therapy strategy delivers significant neuroprotection of both RGC soma and axon and preservation of visual function in the traumatic ON crush model and the SOHU glaucoma model. Collectively, our studies suggest that the weakening of NMNAT2 expression in glaucomatous RGCs contributes to a deleterious NAD+ decline, and that modulating RGC-intrinsic NMNAT2 levels by AAV2-mSncg vector is a promising gene therapy for glaucomatous neurodegeneration.

5f Covalency Synergistically Boosting Oxygen Evolution of UCoO4 Catalyst.

Electronic structure modulation among multiple metal sites is key to the design of efficient catalysts. Most studies have focused on regulating 3d transition-metal active ions through other d-block metals, while few have utilized f-block metals. Herein, we report a new class of catalyst, namely, UCoO4 with alternative CoO6 and 5f-related UO6 octahedra, as a unique example of a 5f-covalent compound that exhibits enhanced electrocatalytic oxygen evolution reaction (OER) activity because of the presence of the U 5f-O 2p-Co 3d network. UCoO4 exhibits a low overpotential of 250 mV at 10 mA cm-2, surpassing other unitary cobalt-based catalysts ever reported. X-ray absorption spectroscopy revealed that the Co2+ ion in pristine UCoO4 was converted to high-valence Co3+/4+, while U6+ remained unchanged during the OER, indicating that only Co was the active site. Density functional theory calculations demonstrated that the OER activity of Co3+/4+ was synergistically enhanced by the covalent bonding of U6+-5f in the U 5f-O 2p-Co 3d network. This study opens new avenues for the realization of electronic structure manipulation via unique 5f involvement.

Silicone Oil-Induced Glaucomatous Neurodegeneration in Rhesus Macaques.

Previously, we developed a simple procedure of intracameral injection of silicone oil (SO) into mouse eyes and established the mouse SOHU (SO-induced ocular hypertension under-detected) glaucoma model with reversible intraocular pressure (IOP) elevation and significant glaucomatous neurodegeneration. Because the anatomy of the non-human primate (NHP) visual system closely resembles that of humans, it is the most likely to predict human responses to diseases and therapies. Here we tried to replicate the mouse SOHU glaucoma model in rhesus macaque monkeys. All six animals that we tested showed significant retinal ganglion cell (RGC) death, optic nerve (ON) degeneration, and visual functional deficits at both 3 and 6 months. In contrast to the mouse SOHU model, however, IOP changed dynamically in these animals, probably due to individual differences in ciliary body tolerance capability. Further optimization of this model is needed to achieve consistent IOP elevation without permanent damage of the ciliary body. The current form of the NHP SOHU model recapitulates the severe degeneration of acute human glaucoma, and is therefore suitable for assessing experimental therapies for neuroprotection and regeneration, and therefore for translating relevant findings into novel and effective treatments for patients with glaucoma and other neurodegenerations.

Mouse γ-Synuclein Promoter-Mediated Gene Expression and Editing in Mammalian Retinal Ganglion Cells.

Optic neuropathies are a group of optic nerve (ON) diseases caused by various insults including glaucoma, inflammation, ischemia, trauma, and genetic deficits, which are characterized by retinal ganglion cell (RGC) death and ON degeneration. An increasing number of genes involved in RGC intrinsic signaling have been found to be promising neural repair targets that can potentially be modulated directly by gene therapy, if we can achieve RGC specific gene targeting. To address this challenge, we first used adeno-associated virus (AAV)-mediated gene transfer to perform a low-throughput in vivo screening in both male and female mouse eyes and identified the mouse γ-synuclein (mSncg) promoter, which specifically and potently sustained transgene expression in mouse RGCs and also works in human RGCs. We further demonstrated that gene therapy that combines AAV-mSncg promoter with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing can knock down pro-degenerative genes in RGCs and provide effective neuroprotection in optic neuropathies.SIGNIFICANCE STATEMENT Here, we present an RGC-specific promoter, mouse γ-synuclein (mSncg) promoter, and perform extensive characterization and proof-of-concept studies of mSncg promoter-mediated gene expression and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing in RGCs in vivo To our knowledge, this is the first report demonstrating in vivo neuroprotection of injured RGCs and optic nerve (ON) by AAV-mediated CRISPR/Cas9 inhibition of genes that are critical for neurodegeneration. It represents a powerful tool to achieve RGC-specific gene modulation, and also opens up a promising gene therapy strategy for optic neuropathies, the most common form of eye diseases that cause irreversible blindness.

Properties of diamane anchored with different groups.

The two-dimensional counterpart of diamond, diamane, has attracted increasing interest due to its potentially distinctive properties. In this paper, diamanes anchored with different anion groups have been systematically studied with density functional theory (DFT) for the first time. Among them 12 conformers are confirmed to be stable and present direct semiconductor features with bandgaps ranging from 2.527 eV to 4.153 eV, and the in-plane stiffness is larger than that of graphene. Moreover, the electron carrier mobility of chair2-F is exceptionally high at 16546.713 cm2 V-1 s-1 along the y-direction, which is remarkably larger than that of diamond; and N-, B-doped boat2-H can be doped to have n-, p-type conductivity with a moderate activation energy of 0.34 and 0.37 eV, respectively. This work suggests that functionalized diamanes are promising for electronic devices and engineering materials.

Contrasting the EXAFS obtained under air and H2 environments to reveal details of the surface structure of Pt-Sn nanoparticles.

Understanding the surface structure of bimetallic nanoparticles is crucial for heterogeneous catalysis. Although surface contraction has been established in monometallic systems, less is known for bimetallic systems, especially of nanoparticles. In this work, the bond length contraction on the surface of bimetallic nanoparticles is revealed by XAS in H2 at room temperature on dealloyed Pt-Sn nanoparticles, where most Sn atoms were oxidized and segregated to the surface when measured in air. The average Sn-Pt bond length is found to be ∼0.09 Šshorter than observed in the bulk. To ascertain the effect of the Sn location on the decrease of the average bond length, Pt-Sn samples with lower surface-to-bulk Sn ratios than the dealloyed Pt-Sn were studied. The structural information specifically from the surface was extracted from the averaged XAS results using an improved fitting model combining the data measured in H2 and in air. Two samples prepared so as to ensure the absence of Sn in the bulk were also studied in the same fashion. The bond length of surface Sn-Pt and the corresponding coordination number obtained in this study show a nearly linear correlation, the origin of which is discussed and attributed to the poor overlap between the Sn 5p orbitals and the available orbitals of the Pt surface atoms.

In vivo evaluation of retinal ganglion cells and optic nerve's integrity in large animals by multi-modality analysis.

Large animal models of optic nerve injury are essential for translating novel findings into effective therapies due to their similarity to humans in many respects. However, most current tests evaluating the integrity of retinal ganglion cells (RGCs) and optic nerve (ON) are based on rodent animal models. We aimed to evaluate and optimize the in vivo methods to assess RGCs and ON's function and structure in large animals in terms of reproducibility, simplicity and sensitivity. Both goats and rhesus macaques were employed in this study. By using goats, we found anesthesia with isoflurane or xylazine resulted in different effects on reproducibility of flash visual evoked potential (FVEP) and pattern electroretinogram (PERG). FVEP with the large-Ganzfeld stimulator was significantly more stable than that with mini-Ganzfeld stimulator. PERG with simultaneous binocular stimulation, with superior simplicity over separate monocular stimulation, was appliable in goats due to undetectable interocular crosstalk of PERG signals. After ON crush in goats, some FVEP components, PERG, OCT and PLR demonstrated significant changes, in line with the histological study. By using rhesus macaque, we found the implicit time of PVEP, FVEP and PERG were significantly more reproducible than amplitudes, and OCT and PLR demonstrated small intersession variation. In summary, we established an optimized system to evaluate integrity of RGCs and ON in large animals in vivo, facilitating usage of large animal models of optic nerve diseases.

A Self-Doped Oxygen-Free High-Critical-Temperature (High-Tc) Superconductor: SmFFeAs.

A new iron-base superconductor SmFFeAs is synthesized via solid-state metathesis reaction by using SmFCl and LiFeAs as precursors. The compound crystallized in the tetragonal ZrCuSiAs-type structure with the space group P4/nmm and lattice parameters of a = 3.9399(0) Å and c = 8.5034(1) Å. The superconducting diamagnetic transition occurs at 56 K for the parent compound, which confirmed by the resistivity and magnetic susceptibility. The appearance of superconductivity without extrinsic doping could be ascribed to the self-doping owing to the mixed valence of Sm ions. The as-synthesized SmFFeAs serves as a new self-doped parent compound for oxygen-free high-critical-temperature (high-Tc) superconductors.

Optical tuning of dielectric properties of La0.7Sr0.3MnO3/SrTiO3 superlattices in the terahertz range.

Two (La0.7Sr0.3MnO3)n/(SrTiO3)m superlattices with different superlattice period but the same total thickness were deposited on LaAlO3 substrates by pulsed laser deposition. Dielectric properties of these samples were investigated by means of terahertz time-domain spectroscopy (THz-TDS) under external continuous wave green laser excitation and optical-pump terahertz-probe spectroscopy (OPTP) at room temperature. Experimental results show that the real part of the permittivity for both superlattices increases significantly with increasing green laser pump power, which indicates the decrease of the plasma frequency, along with the increase of the electron scattering rate, soft mode eigenfrequency and oscillator strength in the Drude-Lorentz model. Furthermore, it's observed that the insulating superlattice exhibits a more significant dielectric tunability than the metallic superlattice. Besides, the carrier lifetime of superlattices is much shorter than the La0.7Sr0.3MnO3 thin film in the OPTP measurements, indicating that the electrons excited in the La0.7Sr0.3MnO3 layers may be trapped by the defects located in the interfaces of La0.7Sr0.3MnO3 and SrTiO3 or the SrTiO3 layers. With the optical field-induced tunability of dielectric properties, (La0.7Sr0.3MnO3)n/(SrTiO3)m superlattices show great potential in the actively tunable devices in the THz range.

Effects of heat treatment atmosphere on the structure and activity of Pt3Sn nanoparticle electrocatalysts: a characterisation case study.

Comprehensive identification of the phases and atomic configurations of bimetallic nanoparticle catalysts are critical in understanding structure-property relationships in catalysis. However, control of the structure, whilst retaining the same composition, is challenging. Here, the same carbon supported Pt3Sn catalyst is annealed under air, Ar and H2 resulting in variation of the extent of alloying of the two components. The atmosphere-induced extent of alloying is characterised using a variety of methods including TEM, XRD, XPS, XANES and EXAFS and is defined as the fraction of Sn present as Sn0 (XPS and XANES) or the ratio of the calculated composition of the bimetallic particle to the nominal composition according to the stoichiometric ratio of the preparation (TEM, XRD and EXAFS). The values obtained depend on the structural method used, but the trend air < Ar < H2 annealed samples is consistent. These results are then used to provide insights regarding the electrocatalytic activity of Pt3Sn catalysts for CO, methanol, ethanol and 1-butanol oxidation and the roles of alloyed Sn and SnO2.

Rescue of Glaucomatous Neurodegeneration by Differentially Modulating Neuronal Endoplasmic Reticulum Stress Molecules.

UNLABELLED: Axon injury is an early event in neurodegenerative diseases that often leads to retrograde neuronal cell death and progressive permanent loss of vital neuronal functions. The connection of these two obviously sequential degenerative events, however, is elusive. Deciphering the upstream signals that trigger the neurodegeneration cascades in both neuronal soma and axon would be a key step toward developing the effective neuroprotectants that are greatly needed in the clinic. We showed previously that optic nerve injury-induced neuronal endoplasmic reticulum (ER) stress plays an important role in retinal ganglion cell (RGC) death. Using two in vivo mouse models of optic neuropathies (traumatic optic nerve injury and glaucoma) and adeno-associated virus-mediated RGC-specific gene targeting, we now show that differential manipulation of unfolded protein response pathways in opposite directions-inhibition of eukaryotic translation initiation factor 2α-C/EBP homologous protein and activation of X-box binding protein 1-promotes both RGC axons and somata survival and preserves visual function. Our results indicate that axon injury-induced neuronal ER stress plays an important role in both axon degeneration and neuron soma death. Neuronal ER stress is therefore a promising therapeutic target for glaucoma and potentially other types of neurodegeneration. SIGNIFICANCE STATEMENT: Neuron soma and axon degeneration have distinct molecular mechanisms although they are clearly connected after axon injury. We previously demonstrated that axon injury induces neuronal endoplasmic reticulum (ER) stress and that manipulation of ER stress molecules synergistically promotes neuron cell body survival. Here we investigated the possibility that ER stress also plays a role in axon degeneration and whether ER stress modulation preserves neuronal function in neurodegenerative diseases. Our results suggest that neuronal ER stress is a general mechanism of degeneration for both neuronal cell body and axon, and that therapeutic targeting of ER stress produces significant functional recovery.

Efficient electrochemical reduction of CO2 to CO in a flow cell device by a pristine Cu5tz6-cluster-based metal-organic framework.

The electrochemical reduction of CO2 to CO is a powerful approach to achieving carbon neutrality. Herein, we report a five-nuclear copper cluster-based metal-azolate framework CuTz-1 as an electrocatalyst for the electrochemical CO2 reduction reaction. It achieved a faradaic efficiency (FE) of 62.7% for yielding CO with a partial current density of -35.1 mA cm-2 in flow cell device, which can be preserved for more than ten hours with negligible changes of the current density and FE(CO). Studies of electrocatalytic mechanism studies revealed that the distance of Cu-N was increased, and the coordination number of the Cu ion was reduced, while the oxidation state of Cu was decreased after the electrocatalysis. These findings offer valuable insights into structural changes that influence the performance of the catalyst during the process of the electrochemical reduction of CO2 process.

Bifunctional Square-Planar NiO4 Coordination of Topotactic LaNiO2.0 Films for Efficient Oxygen Evolution Reaction.

The high-efficient and low-cost oxygen evolution reaction (OER) is decisive for applications of oxide catalysts in metal-air batteries, electrolytic cells, and energy-storage technologies. Delicate regulations of active surface and catalytic reaction pathway of oxide materials principally determine thermodynamic energy barrier and kinetic rate during catalytic reactions, and thus have crucial impacts on OER performance. Herein, a synergistic modulation of catalytically active surface and reaction pathway through facile topotactic transformations switching from perovskite (PV) LaNiO3.0 film to infinite-layer (IL) LaNiO2.0 film is demonstrated, which absolutely contributes to improving OER performance. The square-planar NiO4 coordination of IL-LaNiO2.0 brings about more electrochemically active metal (Ni+ ) sites on the film surface. Meanwhile, the oxygen-deficient driven PV- IL topotactic transformations lead to a reaction pathway converted from absorbate evolution mechanism to lattice-oxygen-mediated mechanism (LOM). The non-concerted proton-electron transfer of LOM pathway, evidenced by the pH-dependent OER kinetics, further boosts the OER activity of IL-LaNiO2.0 films. These findings will advance the in-depth understanding of catalytic mechanisms and open new possibilities for developing highly active perovskite-derived oxide catalysts.

Enhanced polarization switching characteristics of HfO2 ultrathin films via acceptor-donor co-doping.

In the realm of ferroelectric memories, HfO2-based ferroelectrics stand out because of their exceptional CMOS compatibility and scalability. Nevertheless, their switchable polarization and switching speed are not on par with those of perovskite ferroelectrics. It is widely acknowledged that defects play a crucial role in stabilizing the metastable polar phase of HfO2. Simultaneously, defects also pin the domain walls and impede the switching process, ultimately rendering the sluggish switching of HfO2. Herein, we present an effective strategy involving acceptor-donor co-doping to effectively tackle this dilemma. Remarkably enhanced ferroelectricity and the fastest switching process ever reported among HfO2 polar devices are observed in La3+-Ta5+ co-doped HfO2 ultrathin films. Moreover, robust macro-electrical characteristics of co-doped films persist even at a thickness as low as 3 nm, expanding potential applications of HfO2 in ultrathin devices. Our systematic investigations further demonstrate that synergistic effects of uniform microstructure and smaller switching barrier introduced by co-doping ensure the enhanced ferroelectricity and shortened switching time. The co-doping strategy offers an effective avenue to control the defect state and improve the ferroelectric properties of HfO2 films.

Electric field control of perpendicular magnetic tunnel junctions with easy-cone magnetic anisotropic free layers.

Magnetic tunnel junctions (MTJs) are the core element of spintronic devices. Currently, the mainstream writing operation of MTJs is based on electric current with high energy dissipation, and it can be notably reduced if an electric field is used instead. In this regard, it is promising for electric field control of MTJ in the multiferroic heterostructure composed of MTJ and ferroelectrics via strain-mediated magnetoelectric coupling. However, there are only reports on MTJs with in-plane anisotropy so far. Here, we investigate electric field control of the resistance state of MgO-based perpendicular MTJs with easy-cone anisotropic free layers through strain-mediated magnetoelectric coupling in multiferroic heterostructures. A remarkable, nonvolatile, and reversible modulation of resistance at room temperature is demonstrated. Through local reciprocal space mapping under different electric fields for Pb(Mg1/3Nb2/3)0.7Ti0.3O3 beneath the MTJ pillar, the modulation mechanism is deduced. Our work represents a crucial step toward electric field control of spintronic devices with non-in-plane magnetic anisotropy.

Optineurin-facilitated axonal mitochondria delivery promotes neuroprotection and axon regeneration.

Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We found that OPTN C-terminus truncation (OPTN∆C) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a striking decrease of axonal mitochondria. Surprisingly, we discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C-terminus dependent manner. Encouragingly, overexpressing OPTN/TRAK1/KIF5B reverses not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes striking ON regeneration. Therefore, in addition to generating new animal models for NTG and ALS, our results establish OPTN as a novel facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.

Growth-dissolution-regrowth transitions of Fe3O4 nanoparticles as building blocks for 3D magnetic nanoparticle clusters under hydrothermal conditions.

Magnetic nanoparticle clusters (MNCs) are a class of secondary structural materials that comprise chemically defined nanoparticles assembled into clusters of defined size. Herein, MNCs are fabricated through a one-pot solvothermal reaction featuring self-limiting assembly of building blocks and the controlled reorganization process. Such growth-dissolution-regrowth fabrication mechanism overcomes some limitations of conventional solvothermal fabrication methods with regard to restricted available feature size and structural complexity, which can be extended to other oxides (as long as one can be chelated by EDTA-2Na). Based on this method, the nanoparticle size of MNCs is tuned between 6.8 and 31.2 nm at a fixed cluster diameter of 120 nm, wherein the critical size for superparamagnetic-ferromagnetic transition is estimated from 13.5 to 15.7 nm. Control over the nature and secondary structure of MNCs gives an excellent model system to understand the nanoparticle size-dependent magnetic properties of MNCs. MNCs have potential applications in many different areas, while this work evaluates their cytotoxicity and Pb(2+) adsorption capacity as initial application study.