Inhibitory Impact of Prenatal Exposure to Nano-Polystyrene Particles on the MAP2K6/p38 MAPK Axis Inducing Embryonic Developmental Abnormalities in Mice.

Nanoplastics, created by the fragmentation of larger plastic debris, are a serious pollutant posing substantial environmental and health risks. Here, we developed a polystyrene nanoparticle (PS-NP) exposure model during mice pregnancy to explore their effects on embryonic development. We found that exposure to 30 nm PS-NPs during pregnancy resulted in reduced mice placental weight and abnormal embryonic development. Subsequently, our transcriptomic dissection unveiled differential expression in 102 genes under PS-NP exposure and the p38 MAPK pathway emerged as being significantly altered in KEGG pathway mapping. Our findings also included a reduction in the thickness of the trophoblastic layer in the placenta, diminished cell invasion capabilities, and an over-abundance of immature red cells in the blood vessels of the mice. In addition, we validated our findings through the human trophoblastic cell line, HTR-8/SVneo (HTR). PS-NPs induced a drop in the vitality and migration capacities of HTR cells and suppressed the p38 MAPK signaling pathway. This research highlights the embryotoxic effects of nanoplastics on mice, while the verification results from the HTR cells suggest that there could also be certain impacts on the human trophoblast layer, indicating a need for further exploration in this area.

Imaging surface structure and premelting of ice Ih with atomic resolution.

Ice surfaces are closely relevant to many physical and chemical properties, such as melting, freezing, friction, gas uptake and atmospheric reaction1-8. Despite extensive experimental and theoretical investigations9-17, the exact atomic structures of ice interfaces remain elusive owing to the vulnerable hydrogen-bonding network and the complicated premelting process. Here we realize atomic-resolution imaging of the basal (0001) surface structure of hexagonal water ice (ice Ih) by using qPlus-based cryogenic atomic force microscopy with a carbon monoxide-functionalized tip. We find that the crystalline ice-Ih surface consists of mixed Ih- and cubic (Ic)-stacking nanodomains, forming 19 × 19 periodic superstructures. Density functional theory reveals that this reconstructed surface is stabilized over the ideal ice surface mainly by minimizing the electrostatic repulsion between dangling OH bonds. Moreover, we observe that the ice surface gradually becomes disordered with increasing temperature (above 120 Kelvin), indicating the onset of the premelting process. The surface premelting occurs from the defective boundaries between the Ih and Ic domains and can be promoted by the formation of a planar local structure. These results put an end to the longstanding debate on ice surface structures and shed light on the molecular origin of ice premelting, which may lead to a paradigm shift in the understanding of ice physics and chemistry.

Mode-coupled perturbation growth on the interfaces of cylindrical implosion: A comparison between theory and experiment.

We present a mode-coupled weakly nonlinear model for the evolution of perturbations on cylindrical multilayered shells in a decelerating implosion. We show that nonlinear mode-mode interactions among large wave-number fundamental modes are able to induce the growth of small wave number harmonic modes, i.e., forming inverse cascade channels in the wave-number space. When uniform compression and interfacial coupling are taken into consideration, the amplitude of some perturbation modes exhibits an oscillatory growth pattern, which is beyond the intuition that perturbation amplitudes usually have a fast growth tendency in an implosion dominated by the Bell-Plesset effect. Our model accounts well for the previous experiments of Hsing et al. [Hsing et al., Phys. Rev. Lett. 78, 3876 (1997)0031-900710.1103/PhysRevLett.78.3876 and Phys. Plasmas 4, 1832 (1997)1070-664X10.1063/1.872326], which is among the few experiments of multimode multiinterface perturbation development in a cylindrical implosion. In particular, we find that the inverse cascade of modes is the origin of the excitation and growth of the wave number k=2 harmonic mode on the inner interface. The observed decrease of the fundamental modes on the inner interface is mainly attributed to the decreasing period of the oscillatory growth process. These results may afford further insight into the distortion of hot spots in inertial confined fusion implosion near the final stage, and also help to design multimode perturbation experiments in converging geometry in the coming future.

GY-SLAM: A Dense Semantic SLAM System for Plant Factory Transport Robots.

Simultaneous Localization and Mapping (SLAM), as one of the core technologies in intelligent robotics, has gained substantial attention in recent years. Addressing the limitations of SLAM systems in dynamic environments, this research proposes a system specifically designed for plant factory transportation environments, named GY-SLAM. GY-SLAM incorporates a lightweight target detection network, GY, based on YOLOv5, which utilizes GhostNet as the backbone network. This integration is further enhanced with CoordConv coordinate convolution, CARAFE up-sampling operators, and the SE attention mechanism, leading to simultaneous improvements in detection accuracy and model complexity reduction. While mAP@0.5 increased by 0.514% to 95.364, the model simultaneously reduced the number of parameters by 43.976%, computational cost by 46.488%, and model size by 41.752%. Additionally, the system constructs pure static octree maps and grid maps. Tests conducted on the TUM dataset and a proprietary dataset demonstrate that GY-SLAM significantly outperforms ORB-SLAM3 in dynamic scenarios in terms of system localization accuracy and robustness. It shows a remarkable 92.59% improvement in RMSE for Absolute Trajectory Error (ATE), along with a 93.11% improvement in RMSE for the translational drift of Relative Pose Error (RPE) and a 92.89% improvement in RMSE for the rotational drift of RPE. Compared to YOLOv5s, the GY model brings a 41.5944% improvement in detection speed and a 17.7975% increase in SLAM operation speed to the system, indicating strong competitiveness and real-time capabilities. These results validate the effectiveness of GY-SLAM in dynamic environments and provide substantial support for the automation of logistics tasks by robots in specific contexts.

Bridge synergy and simplicial interaction in complex contagions.

Modeling complex contagion in networked systems is an important topic in network science, for which various models have been proposed, including the synergistic contagion model that incorporates coherent interference and the simplicial contagion model that involves high-order interactions. Although both models have demonstrated success in investigating complex contagions, their relationship in modeling complex contagions remains unclear. In this study, we compare the synergy and the simplest form of high-order interaction in the simplicial contagion model, known as the triangular one. We analytically show that the triangular interaction and the synergy can be bridged within complex contagions through the joint degree distribution of the network. Monte Carlo simulations are then conducted to compare simplicial and corresponding synergistic contagions on synthetic and real-world networks, the results of which highlight the consistency of these two different contagion processes and thus validate our analysis. Our study sheds light on the deep relationship between the synergy and high-order interactions and enhances our physical understanding of complex contagions in networked systems.

Treatment of autosomal dominant retinitis pigmentosa caused by RHO-P23H mutation with high-fidelity Cas13X in mice.

Mutations in Rhodopsin (RHO) gene commonly cause autosomal dominant retinitis pigmentosa (adRP) without effective therapeutic treatment so far. Compared with genomic DNA-targeting CRISPR-Cas9 system, Cas13 edits RNA for therapeutic applications, avoiding the risk of causing permanent changes in the genome. In particular, a compact and high-fidelity Cas13X (hfCas13X) recently has been developed to degrade targeted RNA with minimal collateral effects and could also be packaged in a single adeno-associated virus for efficient in vivo delivery. In this study, we engineered single-guide RNA for hfCas13X to specifically knock down human mutant Rhodopsin transcripts RHO-P23H with minimal effect on wild-type transcripts. Moreover, treatment with hfCas13X alleviated the adRP progression in both RHO-P23H overexpression-induced and humanized hRHOP23H/WT mouse models. Our study indicates the potential of hfCas13X in treating adRP caused by RHO mutations and other genetic diseases.

Investigation on the influence of heterogeneous synergy in contagion processes on complex networks.

Synergistic contagion in a networked system occurs in various forms in nature and human society. While the influence of network's structural heterogeneity on synergistic contagion has been well studied, the impact of individual-based heterogeneity on synergistic contagion remains unclear. In this work, we introduce individual-based heterogeneity with a power-law form into the synergistic susceptible-infected-susceptible model by assuming the synergistic strength as a function of individuals' degree and investigate this synergistic contagion process on complex networks. By employing the heterogeneous mean-field (HMF) approximation, we analytically show that the heterogeneous synergy significantly changes the critical threshold of synergistic strength σc that is required for the occurrence of discontinuous phase transitions of contagion processes. Comparing to the synergy without individual-based heterogeneity, the value of σc decreases with degree-enhanced synergy and increases with degree-suppressed synergy, which agrees well with Monte Carlo prediction. Next, we compare our heterogeneous synergistic contagion model with the simplicial contagion model [Iacopini et al., Nat. Commun. 10, 2485 (2019)], in which high-order interactions are introduced to describe complex contagion. Similarity of these two models are shown both analytically and numerically, confirming the ability of our model to statistically describe the simplest high-order interaction within HMF approximation.

A high-fidelity RNA-targeting Cas13 restores paternal Ube3a expression and improves motor functions in Angelman syndrome mice.

Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by loss of function mutations in maternally expressed UBE3A. No gene-specific treatment is available for patients so far. Although intact and transcriptionally active, paternally inherited UBE3A is silenced by elongation of antisense long noncoding RNA UBE3A-ATS in neurons. Here, we demonstrated that RNA targeting of paternal Ube3a-ATS with a high-fidelity CRISPR-Cas13 (hfCas13x.1) system could restore Ube3a expression to similar levels as that of maternal Ube3a in the cultured mouse neurons. Furthermore, injection into lateral ventricles with neuron-specific hSyn1 promoter-driven hfCas13x.1 packaged in adeno-associated virus (AAV-PHP.eb) could restore paternal Ube3a expression in cortex and hippocampus of neonatal AS mice for up to 4 months after treatment. Behavioral tests showed that expression of paternal Ube3a significantly alleviated AS-related symptoms, including obesity and motor function. Our results suggested that hfCas13x.1-mediated suppression of the Ube3a-ATS lncRNA potentially serves as a promising targeted intervention for AS.

Ptbp1 knockdown failed to induce astrocytes to neurons in vivo.

The conversion of non-neuronal cells to neurons is a promising potential strategy for the treatment of neurodegenerative diseases. Recent studies have reported that shRNA-, CasRx-, or ASO-mediated Ptbp1 suppression could reprogram resident astrocytes to neurons. However, some groups have disputed the interpretation of the data underlying the reported neuron conversion events. These controversies surrounding neuron conversion may be due to differences in the astrocyte fate-mapping systems. Here, we suppressed Ptbp1 using Cas13X and labelled astrocytes with an HA tag fused to Cas13X (Cas13X-NLS-HA). We found no astrocyte-to-neuron conversion in the mouse striatum via the HA-tagged labelling system compared with the GFAP-driven tdTomato labelling system (AAV-GFAP::tdTomato-WPRE) used in previous studies. Our findings indicate that Cas13X-mediated Ptbp1 knockdown failed to induce neuron conversion in vivo.

Develop an efficient and specific AAV-based labeling system for Muller glia in mice.

Reprogramming Müller glia (MG) into functional cells is considered a promising therapeutic strategy to treat ocular diseases and vision loss. However, current AAV-based system for MG-tracing was reported to have high leakage in recent studies. Here, we focused on reducing the leakage of AAV-based labeling systems and found that different AAV serotypes showed a range of efficiency and specificity in labeling MG, leading us to optimize a human GFAP-Cre reporter system packaged in the AAV9 serotype with the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) removed. The leakage ratio of the AAV9-hGFAP-Cre-ΔWPRE decreased by an approximate 40-fold compared with the AAV9-hGFAP-Cre-WPRE labeling system. In addition, we validated the specificity of the AAV-ΔWPRE system for tracing MG reprogramming under Ptbp1-suppression and observed strict non-MG-conversion, similar to previous studies using genetic lineage tracking mouse models. Thus, the AAV9-hGFAP-Cre-ΔWPRE system showed high efficiency and specificity for MG labeling, providing a promising tool for tracing cell fate in vivo.

Synergistically Promoting Coking Resistance of a La0.4Sr0.4Ti0.85Ni0.15O3-δ Anode by Ru-Doping-Induced Active Twin Defects and Highly Dispersed Ni Nanoparticles.

The development of anodes with highly efficient electrochemical catalysis and good durability is crucial for solid oxide fuel cells (SOFCs). This paper reports a superior Ru-doped La0.4Sr0.4Ti0.85Ni0.15O3-δ (L0.4STN) anode material with excellent catalytic activity and good stability. The doping of Ru can inhibit the agglomeration of in situ-exsolved Ni nanoparticles on the surface and induce the formation of abundant multiple-twinned defects in the perovskite matrix, which significantly increase the concentration of oxygen vacancies. The reduced L0.4STRN (R-L0.4STRN) anode shows an area-specific resistance (ASR) of 0.067 Ω cm2 at 800 °C, which is only about one-third of that of stochiometric R-L0.6STN (0.212 Ω cm2). A single cell with the R-L0.4STRN anode shows excellent stability (∼50 h at 650 °C) in both H2 and CH4. Furthermore, R-L0.4STRN exhibits outstanding resistance to carbon deposition, which can be attributed to the synergistic effect of highly dispersed Ni nanoparticles and active twinned defects induced by Ru doping.

G9a/GLP-sensitivity of H3K9me2 Demarcates Two Types of Genomic Compartments.

In the nucleus, chromatin is folded into hierarchical architecture that is tightly linked to various nuclear functions. However, the underlying molecular mechanisms that confer these architectures remain incompletely understood. Here, we investigated the functional roles of H3 lysine 9 dimethylation (H3K9me2), one of the abundant histone modifications, in three-dimensional (3D) genome organization. Unlike in mouse embryonic stem cells, inhibition of methyltransferases G9a and GLP in differentiated cells eliminated H3K9me2 predominantly at A-type (active) genomic compartments, and the level of residual H3K9me2 modifications was strongly associated with B-type (inactive) genomic compartments. Furthermore, chemical inhibition of G9a/GLP in mouse hepatocytes led to decreased chromatin-nuclear lamina interactions mainly at G9a/GLP-sensitive regions, increased degree of genomic compartmentalization, and up-regulation of hundreds of genes that were associated with alterations of the 3D chromatin. Collectively, our data demonstrated essential roles of H3K9me2 in 3D genome organization.

TOPORS, a tumor suppressor protein, contributes to the maintenance of higher-order chromatin architecture.

In the nucleus, chromosomes are hierarchically folded into active (A) and inactive (B) compartments composed of topologically associating domains (TADs). Genomic regions interact with nuclear lamina, termed lamina-associated domains (LADs). However, the molecular mechanisms underlying these 3D chromatin architectures remain incompletely understood. Here, we investigated the role of a potential tumor suppressor, TOP1 Binding Arginine/Serine Rich Protein (TOPORS), in genome organization. In mouse hepatocytes, chromatin interactions between A and B compartments increase and compartmentalization strength is reduced significantly upon Topors knockdown. Correspondingly, strength of TAD boundaries located at A/B borders is weakened. In the absence of TOPORS, chromatin-lamina interactions decrease and the coverage of LADs reduces from 53.31% to 46.52%. Interestingly, these changes in 3D genome are associated with PML nuclear bodies and PML-associated domains (PADs). Moreover, chromatin accessibility is altered predominantly at intergenic regions upon Topors knockdown, including a subset of enhancers. These alterations of chromatin are concordant with transcriptome changes, which are associated with carcinogenesis. Collectively, our findings demonstrate that TOPORS functions as a regulator in chromatin structure, providing novel insight into the architectural roles of tumor suppressors in higher-order genome organization.

Eastward shift and extension of ENSO-induced tropical precipitation anomalies under global warming.

During El Niño events, increased precipitation occurs over the equatorial central eastern Pacific, corresponding to enhanced convective heating that modulates global climate by exciting atmospheric teleconnections. These precipitation anomalies are projected to shift and extend eastward in response to global warming. We show that this predicted change is caused by narrowing of the meridional span of the underlying El Niño-related sea surface temperature (SST) anomalies that leads to intensification of the meridional gradient of the SST anomalies, strengthening boundary-layer moisture convergence over the equatorial eastern Pacific, and enhancing local positive precipitation anomalies. The eastward shift and extension of these anomalies also intensify and extend eastward negative precipitation anomalies over the tropical western North Pacific, by strengthening equatorward advection of low mean moist enthalpy. Changes in El Niño-induced tropical precipitation anomalies suggest that, under global warming, El Niño events decay faster after their peak phase, thus shortening their duration.

The Nuclear Matrix Protein SAFB Cooperates with Major Satellite RNAs to Stabilize Heterochromatin Architecture Partially through Phase Separation.

Interphase chromatin is hierarchically organized into higher-order architectures that are essential for gene functions, yet the biomolecules that regulate these 3D architectures remain poorly understood. Here, we show that scaffold attachment factor B (SAFB), a nuclear matrix (NM)-associated protein with RNA-binding functions, modulates chromatin condensation and stabilizes heterochromatin foci in mouse cells. SAFB interacts via its R/G-rich region with heterochromatin-associated repeat transcripts such as major satellite RNAs, which promote the phase separation driven by SAFB. Depletion of SAFB leads to changes in 3D genome organization, including an increase in interchromosomal interactions adjacent to pericentromeric heterochromatin and a decrease in genomic compartmentalization, which could result from the decondensation of pericentromeric heterochromatin. Collectively, we reveal the integrated roles of NM-associated proteins and repeat RNAs in the 3D organization of heterochromatin, which may shed light on the molecular mechanisms of nuclear architecture organization.

Disruption of nuclear speckles reduces chromatin interactions in active compartments.

BACKGROUND: Nuclei of eukaryotes contain various higher-order chromatin architectures and nuclear bodies (NBs), which are critical for proper nuclear functions. Recent studies showed that active chromatin regions are associated with nuclear speckles (NSs), a type of NBs involved in RNA processing. However, the functional roles of NSs in 3D genome organization remain unclear. RESULTS: Using mouse hepatocytes as the model, we knocked down SRRM2, a core protein component scaffolding NSs, and performed Hi-C experiments to examine genome-wide chromatin interactions. We found that Srrm2 depletion disrupted the NSs and changed the expression of 1282 genes. The intra-chromosomal interactions were decreased in type A (active) compartments and increased in type B (repressive) compartments. Furthermore, upon Srrm2 knockdown, the insulation of TADs was decreased specifically in active compartments, and the most significant reduction occurred in A1 sub-compartments. Interestingly, the change of intra-TAD chromatin interactions upon Srrm2 depletion was not associated with the alteration of gene expression. CONCLUSIONS: We show that disruption of NSs by Srrm2 knockdown causes a global decrease in chromatin interactions in active compartments, indicating critical functions of NSs in the organization of the 3D genome.

The Long Noncoding RNA Lncenc1 Maintains Naive States of Mouse ESCs by Promoting the Glycolysis Pathway.

The naive embryonic stem cells (nESCs) display unique characteristics compared with the primed counterparts, but the underlying molecular mechanisms remain elusive. Here we investigate the functional roles of Lncenc1, a highly abundant long noncoding RNA in nESCs. Knockdown or knockout of Lncenc1 in mouse nESCs leads to a significantly decreased expression of core pluripotency genes and a significant reduction of colony formation capability. Furthermore, upon the depletion of Lncenc1, the expression of glycolysis-associated genes is significantly reduced, and the glycolytic activity is substantially impaired, as indicated by a more than 50% reduction in levels of glucose consumption, lactate production, and extracellular acidification rate. Mechanistically, Lncenc1 interacts with PTBP1 and HNRNPK, which regulate the transcription of glycolytic genes, thereby maintaining the self-renewal of nESCs. Our results demonstrate the functions of Lncenc1 in linking energy metabolism and naive state of ESCs, which may enhance our understanding of the molecular basis underlying naive pluripotency.