The Portevin-Le Chatelier Effect of Cu-2.0Be Alloy during Hot Compression.

The Portevin-Le Chatelier effect of Cu-2.0Be alloy was investigated using hot isothermal compression at varying strain rates (0.01-10 s-1) and temperature (903-1063 K). An Arrhenius-type constitutive equation was developed, and the average activation was determined. Both strain-rate-sensitive and temperature-sensitive serrations were identified. The stress-strain curve exhibited three types of serrations: type A at high strain rates, type B (mixed A + B) at medium strain rates, and type C at low strain rates. The serration mechanism is mainly affected by the interaction between the velocity of solute atom diffusion and movable dislocations. As the strain rate increases, the dislocations outpace the diffusion speed of the solute atoms, limiting their ability to effectively pin the dislocations, resulting in lower dislocation density and serration amplitude. Moreover, the dynamic phase transformation triggers the formation of nanoscale dispersive ß phases, which impede dislocation and cause a rapid increase in the effective stress required for unpinning, leading to the formation of mixed A + B serrations at 1 s-1.

Activity-dependent PI4P synthesis by PI4KIIIα regulates long-term synaptic potentiation.

Phosphatidylinositol 4-phosphate (PI4P) is a low abundant phospholipid with important roles in lipid transport and membrane trafficking. However, little is known of its metabolism and function in neurons. Here, we investigate its subcellular distribution and functional roles in dendrites of rodent hippocampal neurons during resting state and long-term synaptic potentiation (LTP). We show that neural activity causes dynamic reversible changes in PI4P metabolism in dendrites. Upon LTP induction, PI4KIIIα, a type III phosphatidylinositol 4-kinase, localizes to the dendritic plasma membrane (PM) in a calcium-dependent manner and causes substantial increase in the levels of PI4P. Acute inhibition of PI4KIIIα activity abolishes trafficking of the AMPA-type glutamate receptor to the PM during LTP induction, and silencing of PI4KIIIα expression in the hippocampal CA1 region causes severe impairment of LTP and long-term memory. Collectively, our results identify an essential role for PI4KIIIα-dependent PI4P synthesis in synaptic plasticity of central nervous system neurons.

The amino-terminal domain of GluA1 mediates LTP maintenance via interaction with neuroplastin-65.

Long-term potentiation (LTP) has long been considered as an important cellular mechanism for learning and memory. LTP expression involves NMDA receptor-dependent synaptic insertion of AMPA receptors (AMPARs). However, how AMPARs are recruited and anchored at the postsynaptic membrane during LTP remains largely unknown. In this study, using CRISPR/Cas9 to delete the endogenous AMPARs and replace them with the mutant forms in single neurons, we have found that the amino-terminal domain (ATD) of GluA1 is required for LTP maintenance. Moreover, we show that GluA1 ATD directly interacts with the cell adhesion molecule neuroplastin-65 (Np65). Neurons lacking Np65 exhibit severely impaired LTP maintenance, and Np65 deletion prevents GluA1 from rescuing LTP in AMPARs-deleted neurons. Thus, our study reveals an essential role for GluA1/Np65 binding in anchoring AMPARs at the postsynaptic membrane during LTP.

The Emerging Picture of the Roles of CircRNA-CDR1as in Cancer.

Circular RNAs (circRNAs) are covalently closed circular structures without 5' caps and 3' tails, which are mainly formed from precursor mRNAs (pre-mRNAs) via back-splicing of exons. With the development of RNA sequencing and bioinformatic analysis, circRNAs were recently rediscovered and found to be widely expressed in the tree of life. Cerebellar degeneration-related protein 1 antisense RNA (CDR1as) is recognized as one of the most well-identified circRNAs. It contains over 70 miR-7 binding sites and can regulate gene activity by sponging miR-7. Increasing numbers of studies have recently demonstrated that CDR1as is abnormally expressed in many types of tumors, such as colorectal cancer, cholangiocarcinoma and osteosarcoma, and plays a vital role in the development of cancer. However, there are few reviews focusing on CDR1as and cancer. Hence, it is important to review and discuss the role of CDR1as in cancer. Here, we first review the main biological features of CDR1as. We then focus on the expression and roles of CDR1as in cancer. Finally, we summarize what is known on the role of CDR1as in cancer and discuss future prospects in this area of research.

Three dimensional printed polylactic acid-hydroxyapatite composite scaffolds for prefabricating vascularized tissue engineered bone: An in vivo bioreactor model.

The repair of large bone defects with complex geometries remains a major clinical challenge. Here, we explored the feasibility of fabricating polylactic acid-hydroxyapatite (PLA-HA) composite scaffolds. These scaffolds were constructed from vascularized tissue engineered bone using an in vivo bioreactor (IVB) strategy with three-dimensional printing technology. Specifically, a rabbit model was established to prefabricate vascularized tissue engineered bone in two groups. An experimental group (EG) was designed using a tibial periosteum capsule filled with 3D printed (3DP) PLA-HA composite scaffolds seeded with bone marrow stromal cells (BMSCs) and crossed with a vascular bundle. 3DP PLA-HA scaffolds were also combined with autologous BMSCs and transplanted to tibial periosteum without blood vessel as a control group (CG). After four and eight weeks, neovascularisation and bone tissues were analysed by studying related genes, micro-computed tomography (Micro-CT) and histological examinations between groups. The results showed that our method capably generated vascularized tissue engineered bone in vivo. Furthermore, we observed significant differences in neovascular and new viable bone formation in the two groups. In this study, we demonstrated the feasibility of generating large vascularized bone tissues in vivo with 3DP PLA-HA composite scaffolds.

HDAC8 functions in spindle assembly during mouse oocyte meiosis.

HDAC8 is a class I histone deacetylase that functions in a variety of biological processes through its non-histone substrates. However, its roles during oocyte meiosis remain elusive. Here, we document that HDAC8 localizes at spindle poles and positively participates in the regulation of microtubule organization and spindle assembly in mouse oocytes. Depletion of HDAC8 by siRNA-based gene silencing results in various spindle defects and chromosome misalignment during oocyte meiotic maturation, accompanied by impaired kinetochore-microtubule attachments. Consequently, a higher incidence of aneuploidy is generated in HDAC8-depleted MII eggs. In addition, inhibition of HDAC8 activity with its selective inhibitor PCI-34051 phenocopies the spindle/chromosome defects resulting from HDAC8 depletion by siRNA injection. Finally, we find that HDAC8 is required for the correct localization of ϕ-tubulin to spindle poles. Collectively, these data reveal that HDAC8 plays a significant role in regulating spindle assembly and thus ensuring the euploidy in mouse eggs.

[Management of secondary nasolabial deformities after bilateral cleft lip repair].

OBJECTIVE: To evaluate the method to correct the seconary nasolabial deformities after the surgical treatment in the patients with bilateral cleft lip. METHODS: From January 2000 to June 2003, forty patients with secondary deformities following repair of bilateral cleft lip were treated with a combined treatment procedures. AU of the forty cases underwent the following preoperative treatments: alveolar bone graft in 28 cases, preoperative orthodontics in 22 cases, prosthodontics in 20 cases and orthognathic surgery or distraction osteogenesis treatment in 20 cases, respectively. In order to improve the enlongation of nasal column, reconstruction of Cupid's bow, philtrum and correction procedures, continuous incision was made from the vermilion in median of the upper lip, the scar edge, the bilateral sides of the nasal column to the inner side of the nose, even extending the bilateral incision to nasolabial groove and nostril fundus. RESULTS: Forty patients were got the follow-ups for 3 months to 3.5 years and the satisfactory rate reached 95%. CONCLUSION: It is natural to emphasize the setting up of odontomaxillary frame and then utilize the surgical procedure to correct the secondary nasolabial parenchyma deformities. The method could be feasible and reliable for the correction of the secondary nasolabial parenchyma deformities after bilateral cleft lip repair.