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Ca 2+ /calmodulin-dependent kinase IIα (CaMKIIα) is essential for synaptic plasticity and learning by decoding synaptic Ca 2+ oscillations. Despite decades of extensive research, new mechanisms underlying CaMKIIα’s function in synapses are still being discovered. Here, we discover that Shank3 is a specific binding partner for autoinhibited CaMKIIα. We demonstrate that Shank3 and GluN2B, via combined actions of Ca 2+ and phosphatases, reciprocally bind to CaMKIIα. Under basal condition, CaMKIIα is recruited to the Shank3 subcompartment of postsynaptic density (PSD) via phase separation. Rise of Ca 2+ concentration induces GluN2B-mediated recruitment of active CaMKIIα and formation of the CaMKIIα/GluN2B/PSD-95 condensates, which are autonomously dispersed upon Ca 2+ removal. Protein phosphatases control the Ca 2+ -dependent shuttling of CaMKIIα between the two PSD subcompartments and PSD condensate formation. Activation of CaMKIIα further enlarges the PSD assembly and induces structural LTP. Thus, Ca 2+ -induced and phosphatase-checked shuttling of CaMKIIα between distinct PSD nano-domains can regulate phase separation-mediated PSD assembly and synaptic plasticity.

This paper illustrates the extent of how education background of parents could affect the relationship between children and parents. The inculcate in children is an essential factor that influences the relationship between children and parents. A strict education method may cause a harsh relationship between a child and his parents, while encouraging education is often beneficial for improving parent-child relationships. Children ‘ s education is decided by the education background of parents, as parents with different education backgrounds would educate child differently. Typically, parents who are well-educated perform better in educating children through a reasonable way. The data in this essay were collected through promoting questionnaires on social media, which uses parent-child sub-scale as the basic questionnaire. What’s more, other evidence from previous researches were also used as a reference to guarantee authenticity. This study assumes that high educated parents can build a better parent-child relationship. Correlation analysis shows that significant positive correlation exists between fathers education background and positive father-child relationship, which is also the same for mothers education background and positive mother-child relationship. Furthermore, non-parametric tests also justifies that the education background of a mother shows a significant positive father-child relationship. These all demonstrates the fact that the more educated the parents are, the better parent-child relationship will be.

The transition from transcription initiation to elongation is highly regulated in human cells but remains incompletely understood at the structural level. In particular, it is unclear how interactions between RNA polymerase (Pol) II and initiation factors are broken to enable promoter escape. Here we reconstitute Pol II promoter escape in vitro, determine high-resolution structures of five transition intermediates, and show that promoter escape occurs in three major steps. First, the growing RNA transcript displaces the B-reader element of the initiation factor TFIIB without evicting TFIIB. Second, rewinding of the upstream edge of the growing DNA bubble evicts TFIIA, TFIIB and TBP and repositions parts of TFIIE and TFIIF. Third, binding of DSIF and NELF evicts TFIIE and TFIIH, establishing the paused elongation complex. This three-step model for promoter escape fills a gap in our understanding of the initiation-elongation transition of Pol II transcription.Competing Interest StatementThe authors have declared no competing interest.

Two-dimensional (2D) semiconducting monolayers such as transition metal dichalcogenides (TMDs) are promising channel materials to extend Moore’s Law in advanced electronics. Synthetic TMD layers from chemical vapor deposition (CVD) are scalable for fabrication but notorious for their high defect densities. Therefore, innovative endeavors on growth reaction to enhance their quality are urgently needed. Here, we report that the hydroxide W species, an extremely pure vapor phase metal precursor form, is very efficient for sulfurization, leading to about one order of magnitude lower defect density compared to those from conventional CVD methods. The field-effect transistor (FET) devices based on the proposed growth reach a peak electron mobility ~200 cm 2 /Vs (~800 cm 2 /Vs) at room temperature (15 K), comparable to those from exfoliated flakes. The FET device with a channel length of 100 nm displays a high on-state current of ~400 µA/µm, encouraging the industrialization of 2D materials. Chemical vapor deposition enables the scalable production of 2D semiconductors, but the grown materials are usually affected by high defect densities. Here, the authors report a hydroxide vapour phase deposition method to synthesize wafer-scale monolayer WS 2 with reduced defect density and electrical properties comparable to those of exfoliated flakes.

Friction stir additive manufacturing technology has emerged as an efficient solid-state process option that provides superior connectivity for lightweight structural material with equiaxed microstructures and outstanding mechanical properties. In this paper, a multilayer ring-shaped build made from 6061-T6 aluminum alloy using friction stir additive manufacturing (FSAM) was characterized. The rotating torque exerted on the friction tool by the surrounding material was measured as it moves to the middle and the end of the ring. Additionally, the correlation between the microstructure and the rotating torque was investigated. The results revealed a significant decrease in rotating torque when the stir tool returned to its original position in the additive zone, leading to a reduction in grain size within the additive zone. Underneath the bottom of the stir zone, there was an overlapping interface filled with deformed grains. Along the horizontal direction, the highest hardness existed in the base material region, while the lowest value appeared in the mixed area of the thermal–mechanical affected zone and heat-affected zone. The hardness value of the stir zone was found to be intermediate between the base material region and the mixed area of the thermal–mechanical affected zone and heat-affected zone. The highest and lowest hardness values along the tool-axial direction were observed at the top of the stir zone and the overlapping interface below it.

The infrastructure construction of bridges is growing rapidly, and the quality of concrete structures is becoming increasingly stringent. However, the issue of cracks in concrete structures remains prominent. In on-site bridge crack detection, the traditional crack identification techniques fail to meet demands due to their inefficiency, inaccuracy, and the challenges posed by high-altitude conditions. In response to this, this paper proposes a bridge crack multi-task integration algorithm based on YOLOv8 object detection and DeepLabv3+ semantic segmentation. This integrated approach offers advantages such as high precision and low inference time. Testing wall cracks using this method, compared to the original approach, resulted in a 10.18% improvement in IOU and a 9.64% improvement in the F1 score. Regarding the detection model, it was deployed on edge computing devices. By applying the TensorRT inference acceleration framework, the camera FPS increased to 9.66, a 59.97% improvement compared to the version without the acceleration framework. This enabled accurate, real-time bridge crack detection on the edge computing devices. Furthermore, the edge computing device was also applied in a self-developed drone, which was tested on-site at the Donghai Bridge, providing a new solution for safe and reliable structural inspection.

Curcumin (Cur) has a short duration of action which limits its therapeutic efficacy. Carbonic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester 4-[7-(4-hydroxy-3-methoxy-phenyl)-3,5-dioxo-hepta-1,6-dienyl]-2-methoxy-phenyl ester (CUD), as a small molecule derivative of Cur with superior stability, has been developed in our laboratory. CUD-loaded solid lipid nanoparticles (CUD-SLN) were prepared to prolong the duration of the drug action of Cur. CUD-SLN were prepared with Poloxamer 188 (F68) and hydrogenated soybean phospholipids (HSPC) as carriers, and the prescription was optimized. The in vitro release of CUD and CUD-SLN was investigated. CUD-SLN (5 mg/kg) was injected into Sprague Dawley (SD) rats to investigate its pharmacokinetic behaviour. CUD-SLN features high entrapment efficiency (96.8 ± 0.4%), uniform particle size (113.0 ± 0.8 nm), polydispersity index (PDI) (0.177 ± 0.007) and an appropriate drug loading capacity (6.2 ± 0.1%). Optimized CUD-SLN exhibited sustained release of CUD for about 48 h. Moreover, the results of the pharmacokinetic studies showed that, compared to Cur, CUD-SLN had a considerably prolonged half-life of 14.7 h, slowed its metabolism in vivo by 35.6-fold, and had an improved area under the curve (AUC 0- t ) of 37.0-fold. CUD-SLN is a promising preparation for the development of a small molecule derivative of Cur.

High-entropy alloy (HEA) coatings on the surface of low-alloy steel by laser cladding can improve the corrosion and wear resistance, and the performance can be further improved by adding the Cr element. However, the effect of Cr content on the microstructure, hardness, wear and corrosion resistance of the coatings on the welded joint has not been completely understood in the literature. This paper aims at revealing the influence of Cr content on the microstructure and properties of laser-cladded FeCoCrxNiAl HEA on different regions of Q345 welded structure. The results indicate that FeCoCrxNiAl HEA coating has good metallurgical bonding with the Q345 welded surface. The increase of Cr element content in the powder plays an important role in energy absorption of powder and substrate, affecting the dilution rate and diffusion of Fe from the substrate to HEA coating. The HEA coating is mainly composed of the face-centered cubic phase (FCC) and body-centered cubic phase (BCC). When x = 1.5, the actual Cr element content of coating is the highest, which promotes the formation of hard brittle phase BCC, and subsequently affects the hardness and wear resistance of the sample. Meanwhile, the corrosion resistance increases and then decreases, and reaches the highest when x = 1.5. Due to the existence of Cr and other elements with good corrosion resistance in the HEA coating, a dense oxide film can be formed in 3.5 wt.% NaCl solution and neutral salt spray environment to prevent the corrosion from continuing, which can effectively improve the corrosion resistance of each region of the welded joint, and the protective efficiencies on the weld bead (WB), heat-affected zone (HAZ) and base metal (BM) are 99.1, 98.4 and 96.6%, respectively.

Interferon γ (IFN–γ) is now considered to be one of the key molecules in the regulation of innate and adaptive immunity. The function of IFN–γ is best described in humans, but less of IFN–γ in fish species has been described at protein level. In the present study, IFN–γ from Gadus macrocephalus (GmIFN–γ) has been examined in terms of bioinformatics, prokaryotic expression, yeast expression, antiviral activity and immune regulatory function. The cDNA of GmIFN–γ contains an open reading frame of 570 nucleotides, coding 189 amino acids. The mature protein contains a nuclear localization signal motif and an obvious IFN–γ signature sequence at the C-terminal. GmIFN–γ is very similar to that of Atlantic cod, with homology up to 89.89%, but less than 32% to other species. GmIFN–γ can be detected in the gills, spleen, intestine, brain and kidney. Interestingly, during early development, a strong signal of GmIFN–γ was not detected until 40 days post hatching. Prokaryotic expression plasmid pET–32a–GmIFN–γ was constructed, and the expression products in BL21 were confirmed by Mass Spectrometry. Meanwhile, the plasmid pGAPZA–GmIFN–γ with Myc tag was constructed and transmitted into Pichia pastoris yeast GS115, and the products were tested using Western blot. The purified GmIFN–γ from either BL21 or yeast has a strong antivirus (Spring viremia of carp virus) effect. The vector of pcDNA3.1–GmIFN–γ was expressed in EPC cell lines; high transcript levels of MHC class I chain-related protein A (MICA) gene were detected; and the exogenous GmIFN–γ protein could also induce MICA expression, indicating that GmIFN–γ could stimulate immune response. The yeast GS115 with GmIFN–γ protein, which is an inclusion body, was given to zebrafish orally, and the transcript of zebrafish IFN–γ was upregulated significantly; however, genes of the interferon type–I signal pathway were not well stimulated.