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Nickel-based superalloys have attracted significant attention due to their outstanding high-temperature strength, corrosion resistance, and oxidation resistance, and are widely used in aerospace and other fields. This article provides a comprehensive review of the preparation methods, common grades, and microstructure and properties of additive manufactured nickel-based superalloys, summarizes the current issues, and proposes future areas for exploration. Nickel-based superalloys prepared by metal additive manufacturing technology have excellent performance, can achieve precise forming of complex components, and have minimal material waste during the manufacturing process. They are expected to become an important production process for nickel-based superalloys components in fields such as aerospace. Common methods for additive manufacturing of nickel-based superalloys include laser powder bed melting, directed energy deposition, and arc additive manufacturing. Powder bed melting is widely used for manufacturing high-precision and complex parts, but it has a relatively slow manufacturing speed and higher equipment and material costs. Directed energy deposition has higher degrees of freedom and flexibility and can be used to prepare functional gradient materials, but it has lower accuracy. Arc additive manufacturing has lower equipment and material costs and is suitable for rapid manufacturing of large parts, but the surface roughness of the alloy produced by this method is poor and requires additional processing or post-treatment. Nickel-based superalloys widely studied in the additive manufacturing process include IN625, Hastelloy X, and other solid solution strengthened alloys, as well as IN718, CM247LC, IN738LC, and other precipitation strengthened superalloys. Compared with traditional casting and forging methods, the unique layer-by-layer forming and rapid cooling and heating process of additive manufacturing result in a coarse columnar grain structure and a unique microstructure with a large number of fine grains. It also forms unique melt pool structures and dislocation cell structures. However, the alloys obtained by additive manufacturing generally require heat treatment to control grain structure and precipitated phases, which affects the mechanical properties of the alloy. In addition, the mechanical properties of additive manufactured nickel-based superalloys are also related to specific preparation methods and alloy types. Although additive manufacturing has been widely used in the preparation of nickel-based superalloys, there are still issues such as anisotropy in microstructure and properties, high sensitivity to alloy cracking, and a lack of corresponding specifications and standards. In the future, further exploration is needed in areas such as heat treatment, customization and development of specialized alloys, investigation of the process-structure-function relationship, and computational modeling.

Porous structures by additive manufacturing have fascinating and compelling performance compared with solid structures. The stress‐related porous infill designs which could greatly mitigate the effects of the intrinsic high residual stress in additive manufacturing process have gained increasing attention. In the current work, we propose a promising Isogeometric Topology Optimization (ITO) method for porous infill structures with stress minimization to avoid the occurrence of stress concentrations in additive manufacturing. The IsoGeometric Analysis (IGA) and induced p‐norm aggregation are utilized to develop a stress‐minimization topology description model for infill design, which can remove the mesh dependency and offer benefits for improving numerical accuracy and convergence stability. We also introduced global volume constraints to easily control the usage of material and eliminate the over‐fine structures affecting the printing accuracy. Several numerical examples are performed to demonstrate the effectiveness and advantages of the proposed ITO method on porous infill designs with stress minimization. The laser powder bed fusion (LPBF) technique is employed to fabricate several prototypes, and the performance are evaluated by experiments. The advancements of our work are demonstrated effectively, which is adapted for additive manufacturing and practical application. [ABSTRACT FROM AUTHOR]

In "inquiry teaching and learning", Dewey regards children as creators and teachers directors. He thinks that children is independent and have a desire to inquire and create, and that children are the persons who are naturally growing and they are creators. The ways that teachers direct children include instructing, guiding, encouraging, helping, suggesting and cooperating, and the time when children lose interest, have some trouble and encounter complex logical arrangements is the golden opportunity for teachers to direct children and offer them help. [ABSTRACT FROM AUTHOR]

Winning increases the readiness to attack and the probability of winning, a widespread phenomenon known as the "winner effect." Here, we reveal a transition from target-specific to generalized aggression enhancement over 10 days of winning in male mice. This behavioral change is supported by three causally linked plasticity events in the ventrolateral part of the ventromedial hypothalamus (VMHvl), a critical node for aggression. Over 10 days of winning, VMHvl cells experience monotonic potentiation of long-range excitatory inputs, transient local connectivity strengthening, and a delayed excitability increase. Optogenetically coactivating the posterior amygdala (PA) terminals and VMHvl cells potentiates the PA-VMHvl pathway and triggers the same cascade of plasticity events observed during repeated winning. Optogenetically blocking PA-VMHvl synaptic potentiation eliminates all winning-induced plasticity. These results reveal the complex Hebbian synaptic and excitability plasticity in the aggression circuit during winning, ultimately leading to increased "aggressiveness" in repeated winners., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Peripheral sensitization is one of the primary mechanisms underlying the pathogenesis of chronic pain. However, candidate molecules involved in peripheral sensitization remain incompletely understood. We have shown that store-operated calcium channels (SOCs) are expressed in the dorsal root ganglion (DRG) neurons. Whether SOCs contribute to peripheral sensitization associated with chronic inflammatory pain is elusive. Here we report that global or conditional deletion of Orai1 attenuates Complete Freund's adjuvant (CFA)-induced pain hypersensitivity in both male and female mice. To further establish the role of Orai1 in inflammatory pain, we performed calcium imaging and patch-clamp recordings in wild-type (WT) and Orai1 knockout (KO) DRG neurons. We found that SOC function was significantly enhanced in WT but not in Orai1 KO DRG neurons from CFA- and carrageenan-injected mice. Interestingly, the Orai1 protein level in L3/4 DRGs was not altered under inflammatory conditions. To understand how Orai1 is modulated under inflammatory pain conditions, prostaglandin E2 (PGE2) was used to sensitize DRG neurons. PGE2-induced increase in neuronal excitability and pain hypersensitivity was significantly reduced in Orai1 KO mice. PGE2-induced potentiation of SOC entry (SOCE) was observed in WT, but not in Orai1 KO DRG neurons. This effect was attenuated by a PGE2 receptor 1 (EP1) antagonist and mimicked by an EP1 agonist. Inhibition of Gq/11, PKC, or ERK abolished PGE2-induced SOCE increase, indicating PGE2-induced SOCE enhancement is mediated by EP1-mediated downstream cascade. These findings demonstrate that Orai1 plays an important role in peripheral sensitization. Our study also provides new insight into molecular mechanisms underlying PGE2-induced modulation of inflammatory pain. Significance Statement Store-operated calcium channel (SOC) Orai1 is expressed and functional in dorsal root ganglion (DRG) neurons. Whether Orai1 contributes to peripheral sensitization is unclear. The present study demonstrates that Orai1-mediated SOC function is enhanced in DRG neurons under inflammatory conditions. Global and conditional deletion of Orai1 attenuates complete Freund's adjuvant (CFA)-induced pain hypersensitivity. We also demonstrate that prostaglandin E2 (PGE2) potentiates SOC function in DRG neurons through EP1-mediated signaling pathway. Importantly, we have found that Orai1 deficiency diminishes PGE2-induced SOC function increase and reduces PGE2-induced increase in neuronal excitability and pain hypersensitivity. These findings suggest that Orai1 plays an important role in peripheral sensitization associated with inflammatory pain. Our study reveals a novel mechanism underlying PGE2/EP1-induced peripheral sensitization. Orai1 may serve as a potential target for pathological pain., (Copyright © 2023 the authors.)

Pathological pain is a common and debilitating condition that is often poorly managed. Central sensitization is an important mechanism underlying pathological pain. However, candidate molecules involved in central sensitization remain unclear. Store-operated calcium channels (SOCs) mediate important calcium signals in nonexcitable and excitable cells. SOCs have been implicated in a wide variety of human pathophysiological conditions, including immunodeficiency, occlusive vascular diseases, and cancer. However, the role of SOCs in CNS disorders has been relatively unexplored. Orai1, a key component of SOCs, is expressed in the human and rodent spinal cord dorsal horn, but its functional significance in dorsal horn neurons is poorly understood. Here we sought to explore a potential role of Orai1 in the modulation of neuronal excitability and A-type potassium channels involved in pain plasticity. Using both male and female Orai1 knock-out mice, we found that activation of Orai1 increased neuronal excitability and reduced A-type potassium channels via the protein kinase C-extracellular signal-regulated protein kinase (PKC-ERK) pathway in dorsal horn neurons. Orai1 deficiency significantly decreased acute pain induced by noxious stimuli, nearly eliminated the second phase of formalin-induced nociceptive response, markedly attenuated carrageenan-induced ipsilateral pain hypersensitivity and abolished carrageenan-induced contralateral mechanical allodynia. Consistently, carrageenan-induced increase in neuronal excitability was abolished in the dorsal horn from Orai1 mutant mice. These findings uncover a novel signaling pathway involved in the pain process and central sensitization. Our study also reveals a novel link among Orai1, ERK, A-type potassium channels, and neuronal excitability. SIGNIFICANCE STATEMENT Orai1 is a key component of store-operated calcium channels (SOCs) in many cell types. It has been implicated in such pathological conditions as immunodeficiency, autoimmunity, and cancer. However, the role of Orai1 in CNS disorders remains poorly understood. The functional significance of Orai1 in neurons is elusive. Here we demonstrate that activation of Orai1 modulates neuronal excitability and Kv4-containing A-type potassium channels via the protein kinase C-extracellular signal-regulated protein kinase (PKC-ERK) pathway. Genetic knock-out of Orai1 nearly eliminates the second phase of formalin-induced pain and markedly attenuates carrageenan-induced pain hypersensitivity and neuronal excitability. These findings reveal a novel link between Orai1 and neuronal excitability and advance our understanding of central sensitization., (Copyright © 2018 the authors 0270-6474/18/380887-14$15.00/0.)

JOURNAL/nrgr/04.03/01300535-202507000-00032/figure1/v/2024-09-09T124005Z/r/image-tiff A microgravity environment has been shown to cause ocular damage and affect visual acuity, but the underlying mechanisms remain unclear. Therefore, we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity. After 4 weeks of tail suspension, there were no notable alterations in retinal function and morphology, while after 8 weeks of tail suspension, significant reductions in retinal function were observed, and the outer nuclear layer was thinner, with abundant apoptotic cells. To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina, proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension. The results showed that the expression levels of fibroblast growth factor 2 (also known as basic fibroblast growth factor) and glial fibrillary acidic protein, which are closely related to Müller cell activation, were significantly upregulated. In addition, Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks, respectively, of simulated weightlessness. These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)

Objective: To establish the model of microdialysis, and study the ocular pharmacokinetics of puerarin in anesthetic rabbits., Method: Implanted the probe into anterior chamber of anesthetic rabbit by surgery. After balanced for 2 h, 1% puerarin eye drop (100 microL) was applied into the cul-de-sac with micropipette. Immediately the dialysate was collected at different time and detected by HPLC with the detection wavelength of 249 nm. The mobile phase was methanol and 0.1% citric acid solution (30:70); the flow rate was 1.0 mL x min(-1)., Result: After the administration, puerarin can be absorbed into aqueous humor quickly. The peak concentration of puerarin appeared at about 1 h and then reduced gradually. The peak concentration(C(max)) is (2.52 +/- 0.31) mg x L(-1). The other lower peak was shown at 3.5 h during the eliminate phase. This might be attributed to the inhibition of aqueous humor production by the puerarin and resulted in a high drug concentration. The area under concentration-time curve (AUC(0-t)) is (5.04 +/- 0.21) mg x h x L(-1) and the eliminate half life (t1/2) is (0.38 +/- 0.13) h., Conclusion: The microdialysis technique can be used to detect the ocular pharmacokinetics of puerarin, and support the valuable pharmacokinetics parameter for the clinical applications of puerarin eye drop.