GSNOR negatively regulates the NLRP3 inflammasome via S-nitrosation of MAPK14.

Hyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous diseases. However, the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely unknown. In this study, we demonstrated that S-nitrosoglutathione reductase (GSNOR) deficiency in macrophages leads to significant increases in the Nlrp3 and Il-1ß expression levels and interleukin-1ß (IL-1ß) secretion in response to NLRP3 inflammasome stimulation. Furthermore, in vivo experiments utilizing Gsnor-/- mice revealed increased disease severity in both lipopolysaccharide (LPS)-induced septic shock and dextran sodium sulfate (DSS)-induced colitis models. Additionally, we showed that both LPS-induced septic shock and DSS-induced colitis were ameliorated in Gsnor-/- Nlrp3-/- double-knockout (DKO) mice. Mechanistically, GSNOR deficiency increases the S-nitrosation of mitogen-activated protein kinase 14 (MAPK14) at the Cys211 residue and augments MAPK14 kinase activity, thereby promoting Nlrp3 and Il-1ß transcription and stimulating NLRP3 inflammasome activity. Our findings suggested that GSNOR is a regulator of the NLRP3 inflammasome and that reducing the level of S-nitrosylated MAPK14 may constitute an effective strategy for alleviating diseases associated with NLRP3-mediated inflammation.

Self-Encapsulation of High-Entropy Alloy Nanoparticles inside Carbonized Wood for Highly Durable Electrocatalysis.

High-entropy alloy nanoparticles (HEAs) show great potential in emerging electrocatalysis due to their combination and optimization of multiple elements. However, synthesized HEAs often exhibit a weak interface with the conductive substrate, hindering their applications in long-term catalysis and energy conversion. Herein, a highly active and durable electrocatalyst composed of quinary HEAs (PtNiCoFeCu) encapsulated inside the activated carbonized wood (ACW) is reported. The self-encapsulation of HEAs is achieved during Joule heating synthesis (2060 K, 2 s) where HEAs naturally nucleate at the defect sites. In the meantime, HEAs catalyze the deposition of mobile carbon atoms to form a protective few-layer carbon shell during the rapid quenching process, thus remarkably strengthening the interface stability between HEAs and ACW. As a result, the HEAs@ACW shows not only favorable activity with an overpotential of 7 mV at 10 mA cm-2 for hydrogen evolution but also negligible attenuation during a 500 h stability test, which is superior to most reported electrocatalysts. The design of self-encapsulated HEAs inside ACW provides a critical strategy to enhance both activity and stability, which is also applicable to many other energy conversion technologies.

Wood-inspired metamaterial catalyst for robust and high-throughput water purification.

Continuous industrialization and other human activities have led to severe water quality deterioration by harmful pollutants. Achieving robust and high-throughput water purification is challenging due to the coupling between mechanical strength, mass transportation and catalytic efficiency. Here, a structure-function integrated system is developed by Douglas fir wood-inspired metamaterial catalysts featuring overlapping microlattices with bimodal pores to decouple the mechanical, transport and catalytic performances. The metamaterial catalyst is prepared by metal 3D printing (316 L stainless steel, mainly Fe) and electrochemically decorated with Co to further boost catalytic functionality. Combining the flexibility of 3D printing and theoretical simulation, the metamaterial catalyst demonstrates a wide range of mechanical-transport-catalysis capabilities while a 70% overlap rate has 3X more strength and surface area per unit volume, and 4X normalized reaction kinetics than those of traditional microlattices. This work demonstrates the rational and harmonious integration of structural and functional design in robust and high throughput water purification, and can inspire the development of various flow catalysts, flow batteries, and functional 3D-printed materials.

Regenerated Graphite Electrodes with Reconstructed Solid Electrolyte Interface and Enclosed Active Lithium Toward >100% Initial Coulombic Efficiency.

Solid electrolyte interface (SEI) is arguably the most important concern in graphite anodes, which determines their achievable Coulombic efficiency (CE) and cycling stability. In spent graphite anodes, there are already-formed (yet loose and/or broken) SEIs and some residual active lithium, which, if can be inherited in the regenerated electrodes, are highly desired to compensate for the lithium loss due to SEI formation. However, current graphite regenerated approaches easily destroy the thin SEIs and residue active lithium, making their reuse impossible. Herein, this work reports a fast-heating strategy (e.g., 1900 K for ≈150 ms) to upcycle degraded graphite via instantly converting the loose original SEI layer (≈100 nm thick) to a compact and mostly inorganic one (≈10-30 nm thick with a 26X higher Young's Modulus) and still retaining the activity of residual lithium. Thanks to the robust SEI and enclosed active lithium, the regenerated graphite exhibited 104.7% initial CE for half-cell and gifted the full cells with LiFePO4 significantly improved initial CE (98.8% versus 83.2%) and energy density (309.4 versus 281.4 Wh kg-1), as compared with commercial graphite. The as-proposed upcycling strategy turns the "waste" graphite into high-value prelithiated ones, along with significant economic and environmental benefits.

Low-Temperature Synthesis of Mesoporous Half-Metallic High-Entropy Spinel Oxide Nanofibers for Photocatalytic CO2 Reduction.

High-entropy oxides (HEOs) exhibit great prospects owing to their varied composition, chemical adaptability, adjustable light-absorption ability, and strong stability. In this study, we report a strategy to synthesize a series of porous high-entropy spinel oxide (HESO) nanofibers (NFs) at a low temperature of 400 °C by a sol-gel electrospinning technique. The key lies in selecting six acetylacetonate salt precursors with similar coordination abilities, maintaining a high-entropy disordered state during the transformation from stable sols to gel NFs. The as-synthesized HESO NFs of (NiCuMnCoZnFe)3O4 show a high specific surface area of 66.48 m2/g, a diverse elemental composition, a dual bandgap, half-metallicity property, and abundant defects. The diverse elements provide various synergistic catalytic sites, and oxygen vacancies act as active sites for electron-hole separation, while the half-metallicity and dual-bandgap structure offer excellent light absorption ability, thus expanding its applicability to a wide range of photocatalytic processes. As a result, the HESO NFs can efficiently convert CO2 into CH4 and CO with high yields of 8.03 and 15.89 µmol g-1 h-1, respectively, without using photosensitizers or sacrificial agents.

Divergent Evolutionary Rates of Primate Brain Regions as Revealed by Genomics and Transcriptomics.

Although the primate brain contains numerous functionally distinct structures that have experienced diverse genetic changes during the course of evolution and development, these changes remain to be explored in detail. Here we utilize two classic metrics from evolutionary biology, the evolutionary rate index (ERI) and the transcriptome age index (TAI), to investigate the evolutionary alterations that have occurred in each area and developmental stage of the primate brain. We observed a higher evolutionary rate for those genes expressed in the non-cortical areas during primate evolution, particularly in human, with the highest rate of evolution being exhibited at brain developmental stages between late infancy and early childhood. Further, the transcriptome age of the non-cortical areas was lower than that of the cerebral cortex, with the youngest age apparent at brain developmental stages between late infancy and early childhood. Our exploration of the evolutionary patterns manifest in each brain area and developmental stage provides important reference points for further research into primate brain evolution.

ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation.

The dorsoventral gradient of BMP signaling plays an essential role in embryonic patterning. Zinc Finger SWIM-Type Containing 4 (zswim4) is expressed in the Spemann-Mangold organizer at the onset of Xenopus gastrulation and is then enriched in the developing neuroectoderm at the mid-gastrula stages. Knockdown or knockout of zswim4 causes ventralization. Overexpression of zswim4 decreases, whereas knockdown of zswim4 increases the expression levels of ventrolateral mesoderm marker genes. Mechanistically, ZSWIM4 attenuates the BMP signal by reducing the protein stability of SMAD1 in the nucleus. Stable isotope labeling by amino acids in cell culture (SILAC) identifies Elongin B (ELOB) and Elongin C (ELOC) as the interaction partners of ZSWIM4. Accordingly, ZSWIM4 forms a complex with the Cul2-RING ubiquitin ligase and ELOB and ELOC, promoting the ubiquitination and degradation of SMAD1 in the nucleus. Our study identifies a novel mechanism that restricts BMP signaling in the nucleus.

Cognitive Deficits and Alzheimer's Disease-Like Pathologies in the Aged Chinese Tree Shrew.

Alzheimer's disease (AD) is the most common chronic progressive neurodegenerative disease in the elderly. It has an increasing prevalence and a growing health burden. One of the limitations in studying AD is the lack of animal models that show features of Alzheimer's pathogenesis. The tree shrew has a much closer genetic affinity to primates than to rodents and has great potential to be used for research into aging and AD. In this study, we aimed to investigate whether tree shrews naturally develop cognitive impairment and major AD-like pathologies with increasing age. Pole-board and novel object recognition tests were used to assess the cognitive performance of adult (about 1 year old) and aged (6 years old or older) tree shrews. The main AD-like pathologies were assessed by Western blotting, immunohistochemical staining, immunofluorescence staining, and Nissl staining. Our results showed that the aged tree shrews developed an impaired cognitive performance compared to the adult tree shrews. Moreover, the aged tree shrews exhibited several age-related phenotypes that are associated with AD, including increased levels of amyloid-ß (Aß) accumulation and phosphorylated tau protein, synaptic and neuronal loss, and reactive gliosis in the cortex and the hippocampal tissues. Our study provides further evidence that the tree shrew is a promising model for the study of aging and AD.

Three-dimensional atomic structure and local chemical order of medium- and high-entropy nanoalloys.

Medium- and high-entropy alloys (M/HEAs) mix several principal elements with near-equiatomic composition and represent a model-shift strategy for designing previously unknown materials in metallurgy1-8, catalysis9-14 and other fields15-18. One of the core hypotheses of M/HEAs is lattice distortion5,19,20, which has been investigated by different numerical and experimental techniques21-26. However, determining the three-dimensional (3D) lattice distortion in M/HEAs remains a challenge. Moreover, the presumed random elemental mixing in M/HEAs has been questioned by X-ray and neutron studies27, atomistic simulations28-30, energy dispersive spectroscopy31,32 and electron diffraction33,34, which suggest the existence of local chemical order in M/HEAs. However, direct experimental observation of the 3D local chemical order has been difficult because energy dispersive spectroscopy integrates the composition of atomic columns along the zone axes7,32,34 and diffuse electron reflections may originate from planar defects instead of local chemical order35. Here we determine the 3D atomic positions of M/HEA nanoparticles using atomic electron tomography36 and quantitatively characterize the local lattice distortion, strain tensor, twin boundaries, dislocation cores and chemical short-range order (CSRO). We find that the high-entropy alloys have larger local lattice distortion and more heterogeneous strain than the medium-entropy alloys and that strain is correlated to CSRO. We also observe CSRO-mediated twinning in the medium-entropy alloys, that is, twinning occurs in energetically unfavoured CSRO regions but not in energetically favoured CSRO ones, which represents, to our knowledge, the first experimental observation of correlating local chemical order with structural defects in any material. We expect that this work will not only expand our fundamental understanding of this important class of materials but also provide the foundation for tailoring M/HEA properties through engineering lattice distortion and local chemical order.

Hydrogenated borophene enabled synthesis of multielement intermetallic catalysts.

Supported metal catalysts often suffer from rapid degradation under harsh conditions due to material failure and weak metal-support interaction. Here we propose using reductive hydrogenated borophene to in-situ synthesize Pt/B/C catalysts with small sizes (~2.5 nm), high-density dispersion (up to 80 wt%Pt), and promising stability, originating from forming Pt-B bond which are theoretically ~5× stronger than Pt-C. Based on the Pt/B/C module, a series (~18 kinds) of carbon supported binary, ternary, quaternary, and quinary Pt intermetallic compound nanocatalysts with sub-4 nm size are synthesized. Thanks to the stable intermetallics and strong metal-support interaction, annealing at 1000 °C does not cause those nanoparticles sintering. They also show much improved activity and stability in electrocatalytic oxygen reduction reaction. Therefore, by introducing the boron chemistry, the hydrogenated borophene derived multielement catalysts enable the synergy of small size, high loading, stable anchoring, and flexible compositions, thus demonstrating high versatility toward efficient and durable catalysis.

Characterization of long-term ex vivo expansion of tree shrew spermatogonial stem cells.

Tree shrews ( Tupaia belangeri chinensis) share a close relationship to primates and have been widely used in biomedical research. We previously established a spermatogonial stem cell (SSC)-based gene editing platform to generate transgenic tree shrews. However, the influences of long-term expansion on tree shrew SSC spermatogenesis potential remain unclear. Here, we examined the in vivo spermatogenesis potential of tree shrew SSCs cultured across different passages. We found that SSCs lost spermatogenesis ability after long-term expansion (>50 passages), as indicated by the failure to colonize the seminiferous epithelium and generate donor spermatogonia (SPG)-derived spermatocytes or spermatids marking spermatogenesis. RNA sequencing (RNA-seq) analysis of undifferentiated SPGs across different passages revealed significant gene expression changes after sub-culturing primary SPG lines for more than 40 passages on feeder layers. Specifically, DNA damage response and repair genes (e.g., MRE11, SMC3, BLM, and GEN1) were down-regulated, whereas genes associated with mitochondrial function (e.g., NDUFA9, NDUFA8, NDUFA13, and NDUFB8) were up-regulated after expansion. The DNA damage accumulation and mitochondrial dysfunction were experimentally validated in high-passage cells. Supplementation with nicotinamide adenine dinucleotide (NAD +) precursor nicotinamide riboside (NR) exhibited beneficial effects by reducing DNA damage accumulation and mitochondrial dysfunction in SPG elicited by long-term culture. Our research presents a comprehensive analysis of the genetic and physiological attributes critical for the sustained expansion of undifferentiated SSCs in tree shrews and proposes an effective strategy for extended in vitro maintenance.

Sabatier Relations in Electrocatalysts Based on High-entropy Alloys with Wide-distributed d-band Centers for Li-O2 Batteries.

Li-O2 battery (LOB) is a promising "beyond Li-ion" technology with ultrahigh theoretical energy density (3457 Wh kg-1 ), while currently impeded by the sluggish cathodic kinetics of the reversible gas-solid reaction between O2 and Li2 O2 . Despite many catalysts are developed for accelerating the conversion process, the lack of design guidance for achieving high performance makes catalysts exploring aleatory. The Sabatier principle is an acknowledged theory connecting the scaling relationship with heterogeneous catalytic activity, providing a tradeoff strategy for the topmost performance. Herein, a series of catalysts with wide-distributed d-band centers (i.e., wide range of adsorption strength) are elaborately constructed via high-entropy strategy, enabling an in-depth study of the Sabatier relations in electrocatalysts for LOBs. A volcano-type correlation of d-band center and catalytic activity emerges. Both theoretical and experimental results indicate that a moderate d-band center with appropriate adsorption strength propels the catalysts up to the top. As a demonstration of concept, the LOB using FeCoNiMnPtIr as catalyst provides an exceptional energy conversion efficiency of over 80 %, and works steadily for 2000 h with a high fixed specific capacity of 4000 mAh g-1 . This work certifies the applicability of Sabatier principle as a guidance for designing advanced heterogeneous catalysts assembled in LOBs.

Integrative Omics Reveals Rapidly Evolving Regulatory Sequences Driving Primate Brain Evolution.

Although the continual expansion of the brain during primate evolution accounts for our enhanced cognitive capabilities, the drivers of brain evolution have scarcely been explored in these ancestral nodes. Here, we performed large-scale comparative genomic, transcriptomic, and epigenomic analyses to investigate the evolutionary alterations acquired by brain genes and provide comprehensive listings of innovatory genetic elements along the evolutionary path from ancestral primates to human. The regulatory sequences associated with brain-expressed genes experienced rapid change, particularly in the ancestor of the Simiiformes. Extensive comparisons of single-cell and bulk transcriptomic data between primate and nonprimate brains revealed that these regulatory sequences may drive the high expression of certain genes in primate brains. Employing in utero electroporation into mouse embryonic cortex, we show that the primate-specific brain-biased gene BMP7 was recruited, probably in the ancestor of the Simiiformes, to regulate neuronal proliferation in the primate ventricular zone. Our study provides a comprehensive listing of genes and regulatory changes along the brain evolution lineage of ancestral primates leading to human. These data should be invaluable for future functional studies that will deepen our understanding not only of the genetic basis of human brain evolution but also of inherited disease.

Measurement of Nanoscale Film Thickness Using Neutron Depth Profiling Technique.

Determination of geometric parameters for thin film materials has always been a critical concern in scientific research. This paper proposes a novel approach for high-resolution and nondestructive measurement of nanoscale film thickness. In this study, the neutron depth profiling (NDP) technique was employed to accurately measure the thickness of nanoscale Cu films, achieving an impressive resolution of up to 1.78 nm/keV. The measurement results exhibited a deviation from the actual thickness of less than 1%, highlighting the accuracy of the proposed method. Additionally, simulations were conducted on graphene samples to demonstrate the applicability of NDP in measuring the thickness of multilayer graphene films. These simulations provide a theoretical foundation for subsequent experimental measurements, further enhancing the validity and practicality of the proposed technique.

Coexistence of Multiple Functional Variants and Genes Underlies Genetic Risk Locus 11p11.2 of Alzheimer's Disease.

BACKGROUND: Genome-wide association studies have identified dozens of genetic risk loci for Alzheimer's disease (AD), yet the underlying causal variants and biological mechanisms remain elusive, especially for loci with complex linkage disequilibrium and regulation. METHODS: To fully untangle the causal signal at a single locus, we performed a functional genomic study of 11p11.2 (the CELF1/SPI1 locus). Genome-wide association study signals at 11p11.2 were integrated with datasets of histone modification, open chromatin, and transcription factor binding to distill potentially functional variants (fVars). Their allelic regulatory activities were confirmed by allele imbalance, reporter assays, and base editing. Expressional quantitative trait loci and chromatin interaction data were incorporated to assign target genes to fVars. The relevance of these genes to AD was assessed by convergent functional genomics using bulk brain and single-cell transcriptomic, epigenomic, and proteomic datasets of patients with AD and control individuals, followed by cellular assays. RESULTS: We found that 24 potential fVars, rather than a single variant, were responsible for the risk of 11p11.2. These fVars modulated transcription factor binding and regulated multiple genes by long-range chromatin interactions. Besides SPI1, convergent evidence indicated that 6 target genes (MTCH2, ACP2, NDUFS3, PSMC3, C1QTNF4, and MADD) of fVars were likely to be involved in AD development. Disruption of each gene led to cellular amyloid-ß and phosphorylated tau changes, supporting the existence of multiple likely causal genes at 11p11.2. CONCLUSIONS: Multiple variants and genes at 11p11.2 may contribute to AD risk. This finding provides new insights into the mechanistic and therapeutic challenges of AD.

Eighty million years of rapid evolution of the primate Y chromosome.

The Y chromosome usually plays a critical role in determining male sex and comprises sequence classes that have experienced unique evolutionary trajectories. Here we generated 19 new primate sex chromosome assemblies, analysed them with 10 existing assemblies and report rapid evolution of the Y chromosome across primates. The pseudoautosomal boundary has shifted at least six times during primate evolution, leading to the formation of a Simiiformes-specific evolutionary stratum and to the independent start of young strata in Catarrhini and Platyrrhini. Different primate lineages experienced different rates of gene loss and structural and chromatin change on their Y chromosomes. Selection on several Y-linked genes has contributed to the evolution of male developmental traits across the primates. Additionally, lineage-specific expansions of ampliconic regions have further increased the diversification of the structure and gene composition of the Y chromosome. Overall, our comprehensive analysis has broadened our knowledge of the evolution of the primate Y chromosome.

Phylogenomic analyses provide insights into primate evolution.

Comparative analysis of primate genomes within a phylogenetic context is essential for understanding the evolution of human genetic architecture and primate diversity. We present such a study of 50 primate species spanning 38 genera and 14 families, including 27 genomes first reported here, with many from previously less well represented groups, the New World monkeys and the Strepsirrhini. Our analyses reveal heterogeneous rates of genomic rearrangement and gene evolution across primate lineages. Thousands of genes under positive selection in different lineages play roles in the nervous, skeletal, and digestive systems and may have contributed to primate innovations and adaptations. Our study reveals that many key genomic innovations occurred in the Simiiformes ancestral node and may have had an impact on the adaptive radiation of the Simiiformes and human evolution.