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Metabolic disorder significantly contributes to diabetic vascular complications, including diabetic retinopathy, the leading cause of blindness in the working-age population. However, the molecular mechanisms by which disturbed metabolic homeostasis causes vascular dysfunction in diabetic retinopathy remain unclear. O- GlcNAcylation modification acts as a nutrient sensor particularly sensitive to ambient glucose. Here, we observe pronounced O- GlcNAc elevation in retina endothelial cells of diabetic retinopathy patients and mouse models. Endothelial-specific depletion or pharmacological inhibition of O- GlcNAc transferase effectively mitigates vascular dysfunction. Mechanistically, we find that Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-binding motif (TAZ), key effectors of the Hippo pathway, are O- GlcNAcylated in diabetic retinopathy. We identify threonine 383 as an O- GlcNAc site on YAP, which inhibits its phosphorylation at serine 397, leading to its stabilization and activation, thereby promoting vascular dysfunction by inducing a pro-angiogenic and glucose metabolic transcriptional program. This work emphasizes the critical role of the O- GlcNAc-Hippo axis in the pathogenesis of diabetic retinopathy and suggests its potential as a therapeutic target. Metabolic disorder significantly contributes to diabetic vascular complications, including diabetic retinopathy (DR). This study reveals that O -GlcNAcylation, a nutrient-sensitive protein modification, drives vascular dysfunction in DR by stabilizing Hippo signaling key components YAP/TAZ. Targeting O -GlcNAc-YAP/TAZ shows therapeutic potential for mitigating DR pathology.

Amyloid β (Aβ) oligomer-induced aberrant neurotransmitter release is proposed to be a crucial early event leading to synapse dysfunction in Alzheimer’s disease (AD). In the present study, we report that the release probability (Pr) at the synapse between the Schaffer collateral (SC) and CA1 pyramidal neurons is significantly reduced at an early stage in mouse models of AD with elevated Aβ production. High nanomolar synthetic oligomeric Aβ 42 also suppresses Pr at the SC-CA1 synapse in wild-type mice. This Aβ-induced suppression of Pr is mainly due to an mGluR5-mediated depletion of phosphatidylinositol-4,5-bisphosphate (PIP 2 ) in axons. Selectively inhibiting Aβ-induced PIP 2 hydrolysis in the CA3 region of the hippocampus strongly prevents oligomeric Aβ-induced suppression of Pr at the SC-CA1 synapse and rescues synaptic and spatial learning and memory deficits in APP/PS1 mice. These results first reveal the presynaptic mGluR5-PIP 2 pathway whereby oligomeric Aβ induces early synaptic deficits in AD. The underlying mechanism of amyloid β (Aβ) oligomer-induced aberrant neurotransmitter release remains unclear. Here, authors show that the release probability at the synapse between the Schaffer collateral and CA1 pyramidal neurons is significantly reduced at an early stage in mouse models of AD with elevated Aβ production and is mainly due to an mGluR5-mediated depletion of PIP2 in axons.

With severe soil and water erosion, the crucial ion-adsorption rare earth elements (REEs) have attracted much global attention. REEs play a vital role in tracing material sources and exploring sedimentary characteristics due to their unique and stable geochemistry properties. In the present work, three representational possible redeposition areas in western Fujian were selected as the study areas. The geochemical characteristics of REEs in the sediments of the study areas were evaluated to elucidate that REEs are the products of soil and water erosion and to assess their redeposition characteristics. In the research results, the properties of the parent rocks shown in the samples, together with the negative correlation between the content of REEs in the samples and altitude as well as the relief degree on the land surface (RDLS), fully indicate that the sediments in the study areas are the products of migration caused by soil erosion and redeposition in the downstream areas. At the same time, according to the widely applicable standard of rare earth resources exploitation, that is the boundary grade of ion-adsorption rare earth ore in southern China (∑REE = 500 mg·kg −1 ), we found that the content of REEs in the study areas was close to or exceeded this standard, and the maximum ∑REE of Guozhai Reservoir (869.11 mg·kg −1 ) was much larger than this standard. Therefore, the redeposited rare earth in Changting Country has high reuse potential under the current scarce resources.

Low carbon MnCrMoNiCu alloyed steels are typically used to produce highly ductile thick plates for offshore structures and bulk shipbuilding. The current study revealed how microscopic factors affect the toughness and the occurrence of cleavage fracture of the steel. In this regard, a series of thermal treatments was performed on the test steel by employing a thermomechanical simulator. These involved reheating samples at different temperatures (1168 K to 1623 K (895 °C to 1350 °C)) producing different prior austenite grain sizes, followed by a continuous cooling transformation process. The Charpy V notch (CVN) toughness was determined, and the effect of the austenite grain size on the ductile–brittle transition-temperatures of the steel was investigated. The microstructural evolution of the austenite grain sizes was studied, fracture features were characterized, the critical event for cleavage fracture was identified, and the local cleavage fracture stress σf was calculated. The CVN toughness and σf were maximized in the steel which was reheated at 1273 K (1000 °C) and containing refined lathlike bainite.

HSLA-100 steel with high content of alloying elements (nominally in wt pct, 3.5 Ni, 1.6 Cu, and 0.6Mo) is now used to produce heavy plates for constructing a hull and drilling platform. We proposed here a substantially leaner steel composition (containing 1.7 Ni, 1.1 Cu, and 0.5Mo) to produce a heavy plate to 80 mm thickness with mechanical properties comparable with those of the HSLA-100 grade. A continuous cooling transformation (CCT) diagram of the steel was constructed. Key parameters of thermal treatment and revealing mechanisms of strengthening and toughening were derived based on industrial production trials. The microstructures of the 80-mm-thick plate were lath-like bainite (LB) at near surface of the quarter thickness ( t /4), and granular bainite (GB)+LB at center thickness ( t /2) after solutionizing and water quenching (Q). The effect of tempering (T) on the microstructures and properties of the plate was investigated. Excellent combination of room temperature strength and low-temperature Charpy V-notch (CVN) toughness approximately equivalent to that of the HSLA 100 grade (YS > 690 MPa, CVN energy >100 J even at 193 K [−80 °C]) was achieved in the plate treated by the QT process with tempering temperature of 898 K (625 °C). The combination of strength and toughness at t /4 is superior to that at t /2 of the plate under both as-quenched and QT conditions. This result is attributed to that the fraction of high-angle grain boundaries (HAGBs) at t /4 is higher than that at t /2.

Exosomes, a type of extracellular vesicle, have been shown to be involved in many disorders, including Alzheimer's disease (AD). Exosomes may contribute to the spread of misfolded proteins such as amyloid-β (Aβ) and α-synuclein. However, the specific diffusion process of exosomes and their final destination in brain are still unclear. In the present study, we isolated exosomes from peripheral plasma and injected them into the hippocampus of an AD mouse model, and investigated exosome diffusion. We found that injected exosomes can spread from the dentate gyrus (DG) to other regions of hippocampus and to the cortex. Exosomes targeted microglia preferentially; this phenomenon is stable and is not affected by age. In AD mice, microglia take up lower levels of exosomes. More interestingly, plasma exosomes cluster around the Aβ plaques and are engulfed by activated microglia nearby. Our data indicate that exosomes can diffuse throughout the brain and may play a role in the dynamics of amyloid deposition in AD through microglia.

In the original article the following errors occurred: In the last sentence of the first paragraph in the Experimental Procedures section, 11 mm × 1 mm × 75 mm is incorrect. The correction dimensions are 11 mm × 11 mm × 75 mm.

Recently, reconfigurable intelligent surface (RIS) has been widely used to enhance the performance of millimeter wave (mmWave) communication systems, making beam alignment more challenging. To ensure efficient communication, this paper proposes a novel intelligent angle map-based beam alignment scheme for both general user equipments (UEs) and RIS-aided UEs simultaneously in a fast and effective way. Specifically, we construct a beam alignment architecture that utilizes only angular information. To obtain the angle information, the currently hottest seq2seq model - the Transformer - is introduced to offline learn the relationship between UE geographic location and the corresponding optimal beam direction. Based on the powerful machine learning model, the location-angle mapping function, i.e., the angle map, can be built. As long as the location information of UEs is available, the angle map can make the acquisition of beam alignment angles effortless. In the simulation, we utilize a ray-tracing-based dataset to verify the performance of the proposed scheme. It is demonstrated that the proposed scheme can achieve high-precision beam alignment and remarkable system performance without any beam scanning.

Hippocampal neurogenesis declines with aging. Wnt ligands and antagonists within the hippocampal neurogenic niche regulate the proliferation of neural progenitor cells and the development of new neurons, and the changes of their levels in the niche mediate aging-associated decline of neurogenesis. We found that RNA-binding protein Lin28a remained existent in neural progenitor cells and granule neurons in the adult hippocampus, and decreased with aging. Loss of Lin28a inhibited the responsiveness of neural progenitor cells to niche Wnt agonist and reduced neurogenesis, thus impairing pattern separation. Overexpression of Lin28a increased the proliferation of neural progenitor cells, promoted the functional integration of newborn neurons, restored neurogenesis in Wnt-deficient dentate gyrus, and rescued the impaired pattern separation in aging mice. Our data suggest that Lin28a regulates adult hippocampal neurogenesis as an intracellular mechanism by responding to niche Wnt signals, and its decrease is involved in aging-associated decline of hippocampal neurogenesis as well as related cognitive functions.