Optimisation of Selective Laser Melted Ti6Al4V Functionally Graded Lattice Structures Accounting for Structural Safety.

This paper presents a new framework for lightweight optimisation of functionally graded lattice structures (FGLSs) with a particular focus on enhancing and guaranteeing structural safety through three main contributions. Firstly, a design strategy of adding fillets to the joints of body-centred cubic (BCC) type lattice cells was proposed to improve the effective yield stress of the lattices. Secondly, effective properties of lattice metamaterials were experimentally characterised by conducting quasi-static uniaxial compression tests on selective laser melted specimens of both Ti6Al4V BCC and filleted BCC (BCC-F) lattices with different relative densities. Thirdly, a yield stress constraint for optimising FGLSs was developed based on surrogate models quantifying the relationships between the relative density and the effective properties of BCC and BCC-F lattices developed using experimental results assisted by numerical homogenisation. This framework was tested with two case studies. Results showed that structural safety with respect to avoiding yield failure of the optimised FGLSs can be ensured and the introduction of fillets can effectively improve the strength-to-weight ratio of the optimised FGLSs composed of BCC type lattices. The BCC-F FGLS achieved 14.5% improvement in weight reduction compared with BCC FGLS for the Messerschmitt-Bölkow-Blohm beam optimisation case study.

[Intervention effect of lipoxygen receptor agonist BML-111 on acute liver injury in rats and its mechanism].

Objective: To investigate the effect and mechanism of lipoxygen on acute liver injury. Methods: Twenty-four SD rats were randomly divided into 4 groups (n=6): normal control group: subcutaneous injection of olive oil at a dose of 1.8 ml/kg; model group: subcutaneous injection of 40% carbon tetrachloride(CCL4)oil (olive oil as a solvent) at a dose of 3 ml/kg; BML-111 treatment group: Lipoxin receptor agonist BML-111 was injected subcutaneously at a dose of 1 mg/kg, and treated in the same model group after 30 minutes; BOC-2 blocker group: Lipoxin receptor blocker BOC-2 was injected subcutaneously at a dose of 50 µg/kg. After 30 minutes, the treatment was the same as BML-111 group. HE staining was used to observe the pathological changes of liver tissues to judge the liver injury. Serological detection was used to determine the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST); The myeloperoxidase (MPO) activity in rat liver tissue was detected by kit method; the contents of of angiotensin converting enzyme (ACE) , Angiotensin converting enzyme 2 (ACE2), angiotensin II (AngII) and angiotensin 1-7 (Ang- (1-7)) were detected by ELISA. Western Blot was used to detect the protein contents of Ang II and Ang- (1-7) in liver tissue. Results: The treatment group had less liver damage than the model group and the blocker group; BML-111 decreased the levels of ACE and AngII in serum of rats with CCL4 injury (P＜0.01) and increased the levels of ACE2 and Ang- (1 in serum -7) content (P＜0.01). BML-111 increased the content of Ang- (1-7) in liver tissue and decreased the content of AngII in CCL4 injured rat tissue. Conclusion: The results showed that the intervention effect and mechanism of lipoxygen receptor agonist BML-111 on acute liver injury in rats may be related to the regulation of AngII and Ang-(1-7).

BML-111, a lipoxin receptor agonist, protects against acute injury via regulating the renin angiotensin-aldosterone system.

BACKGROUND: The renin angiotensin-aldosterone system (RAAS) and lipoxins (LXs) have similar roles in many processes. We previously reported that BML-111, a Lipoxin receptor agonist, inhibited chronic injury hepatic fibrosis by regulating RAAS, but whether LXs are involved in BML-111-mediated protection from acute injury is unclear still. METHODS: We established models of acute liver/lung injury and confirmed them with histopathology and myeloperoxidase (MPO) measurements. BML-111, a lipoxin receptor agonist, was applied to mimic the effects of LXs. The contents and activities of angiotensin converting enzyme(ACE) and angiotensinconverting enzyme 2 (ACE2) were measured through ELISA and activity assay kits respectively. Angiotensin II (AngII), angiotensin-(1-7) (Ang-1-7), AngII type 1 receptor (AT1R), and Mas receptor were quantified with ELISA and Western blot. RESULTS: Models of acute injury were established successfully and BML-111 protected LPS-induced acute lung injury and LPS/D-GalN-induced acute liver injury. BML-111 repressed the activity of ACE, but increased the activity of ACE2. BML-111 decreased the expression levels of ACE, AngII, and AT1R, meanwhile increased the levels of ACE2, Ang-(1-7), and Mas. Furthermore, BOC-2, an inhibitor of lipoxin receptor, reversed all the effects. CONCLUSION: BML-111 could protect against acute injury via regulation RAAS.

BML-111 equilibrated ACE-AngII-AT1R and ACE2-Ang-(1-7)-Mas axis to protect hepatic fibrosis in rats.

BACKGROUND: It was recently reported Lipoxins (LXs) had protective effects on fibrous diseases, and renin-angiotensin-aldosterone system (RAAS) had played vital and bidirectional roles in hepatic fibrosis. In this paper, a hepatic fibrosis model, induced by carbon tetrachloride (CCL4) in rats, was used to observe the relations between RAAS and LXs, as well as to further explore the alternative anti-fibrosis mechanisms of LXs. METHODS: The model was evaluated by morphological observations and biochemical assays. The activities and contents of angiotensin converting enzyme (ACE) and angiotensin converting enzyme 2 (ACE2) were examined through assay kits and ELISA. The expression levels of angiotensinII (AngII), Angiotensin II type 1 receptor (AT1R), angiotensin-(1-7) (Ang-1-7), and Mas were all measured using real time PCR, ELISA, and Western blot. RESULTS: The model was established successfully and BML-111 significantly ameliorated CCL4-induced hepatic fibrosis, including reduction inflammation injury, decrease extracellular matrix deposition, and improvement hepatic functions. Furthermore, BML-111 could obviously decrease not only the activities of ACE but also the expression levels of ACE, AngII,and AT1R, which were induced by CCL4. On the other hand, BML-111 could markedly increase the activities of ACE2, besides the expression levels of ACE2, Ang-(1-7) and Mas. More importantly, BOC-2, a lipoxin A4 receptor blocker, could reverse all these phenomena. CONCLUSIONS: Equilibrating ACE-AngII-AT1R axis and ACE2-Ang-(1-7)-Mas axis mediated the protective effect of BML-111 on hepatic fibrosis in rats.