Optimization of Forged 42CrMo4 Steel Piston Pin Hole Profile Using Finite Element Method

The fatigue failure of the piston pin hole is considered as a key factor affecting the service life of engines. In this work, the piston pin hole profile was designed as tapered shape following a power law. By combining finite element analysis and hydraulic pulsating fatigue tests, the pin hole profile was optimized. It has been found that the maximum contact pressure on the pin hole surface was reduced by 16,7% with appropriate increasing the radius enlarging rate of the piston pin hole, the maximum tensile stress of the piston pin seat was reduced by 13,1%, and the piston pin seat fatigue safety factor was increased by 41,4%, the piston pin hole fatigue safety factor was increased by 15,9%. The piston pin hole’s hydraulic pulsating fatigue test results were found to be consistent with the FEA results. It could be concluded that appropriate increasing the radius enlarging rate of the pin hole could significantly weaken the fatigue wear of the pin hole, further improving its fatigue resistance

Shape memory polyurethane microcapsules with active deformation

From smart self-tightening sutures and expandable stents to morphing airplane wings, shape memory structures are increasingly present in our daily life. The lack of methods for synthesizing intricate structures from them on the micron and submicron level, however, is stopping the field from developing. In particular, the methods for the synthesis of shape memory polymers (SMPs) and structures at this scale and the effect of new geometries remain unexplored. Here, we describe the synthesis of shape memory polyurethane (PU) capsules accomplished by interfacial polymerization of emulsified droplets. The emulsified droplets contain the monomers for the hard segments, while the continuous aqueous phase contains the soft segments. A trifunctional chemical cross-linker for shape memory PU synthesis was utilized to eliminate creep and improve the recovery ratios of the final capsules. We observe an anomalous dependence of the recovery ratio with the amount of programmed strain compared to previous SMPs. We develop quantitative characterization methods and theory to show that when dealing with thin-shell objects, alternative parameters to quantify recovery ratios are needed. We show that while achieving 94-99% area recovery ratios, the linear capsule recovery ratios can be as low as 70%. This quantification method allows us to convert from observed linear aspect ratios in capsules to find out unrecovered area strain and stress. The hollow structure of the capsules grants high internal volume for some applications (e.g., drug delivery), which benefit from much higher loading of active ingredients than polymeric particles. The methods we developed for capsule synthesis and programming could be easily scaled up for larger volume applications

Using noble gases to trace groundwater evolution and assess helium accumulation in Weihe Basin, central China

The severe shortage of helium resources is an impending global problem. However, the helium accumulation processes and conditions favorable for helium enrichment in reservoirs remain poorly understood, which makes helium exploration challenging. Noble gases are good tracers of subsurface fluids provenance, migration and storage, as well as indicators of the nature and quantity of associated phases. In this study the variation of major gases and noble gases data in Weihe Basin provide us with an excellent opportunity to understand the groundwater evolution and helium accumulation processes. Twelve gas samples collected from wellheads of geothermal wells can be classified into three groups, in which Group A has high concentrations of N2 (58.57% - 91.66%) and He (0.32% - 2.94%); Group B has high contents of CH4 (52.94% and 69.50%) and low concentrations of He (0.057% and 0.062%); Group C has a high content of CH4 (71.70%) and He (2.11%). Helium isotopic ratios are predominantly radiogenic in origin and therefore crustally derived. Measured elemental ratios of noble gases are compared with multiple fractionation models for Group A and B samples, implying that open system heavy oil-water fractionation with excess heavy noble gases has occurred in the basin with Voil/Vwater ratios of 0.06-0.18. The amount of helium in Group A and B samples requires the release of all 4He produced in the crust since 0.30Ma-1.98Ma into the groundwater. The Group C sample requires an additional He flux from adjacent granitic bodies. The accumulation of helium and hydrocarbon in the Weihe Basin can be explained by a 4-stage process. Accumulation of commercially viable helium requires high He flux from source rocks, the existence of a free gas phase of major gas components (CH4 in most cases, N2 or CO2) and minimal major gas addition after formation of the free gas phase

Simulation study of a high‐performance brain PET system with dodecahedral geometry

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145295/1/mp12996_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145295/2/mp12996.pd

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

<p>Abstract</p> <p>Background</p> <p>Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN) are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN.</p> <p>Methods</p> <p>Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw) with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD₅₀) was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw) was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters.</p> <p>Results</p> <p>After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group.</p> <p>Conclusions</p> <p>The results revealed that the LD₅₀of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the nanoparticles are considered low toxic according to the toxicity categories of chemicals. Moreover, HCO-SLN significantly decreased the toxicity of tilmicosin. Normal clinic dosage of Til-HCO-SLN is safe as evaluated by acute toxicity.</p

An in vitro model of fibrosis using crosslinked native extracellular matrix-derived hydrogels to modulate biomechanics without changing composition

Extracellular matrix (ECM) is a dynamic network of proteins, proteoglycans and glycosaminoglycans, providing structure to the tissue and biochemical and biomechanical instructions to the resident cells. In fibrosis, the composition and the organization of the ECM are altered, and these changes influence cellular behaviour. Biochemical (i. e. protein composition) and biomechanical changes in ECM take place simultaneously in vivo. Investigating these changes individually in vitro to examine their (patho)physiological effects has been difficult. In this study, we generated an in vitro model to reflect the altered mechanics of a fibrotic microenvironment through applying fibre crosslinking via ruthenium/sodium persulfate crosslinking on native lung ECM-derived hydrogels. Crosslinking of the hydrogels without changing the biochemical composition of the ECM resulted in increased stiffness and decreased viscoelastic stress relaxation. The altered stress relaxation behaviour was explained using a generalized Maxwell model. Fibre analysis of the hydrogels showed that crosslinked hydrogels had a higher percentage of matrix with a high density and a shorter average fibre length. Fibroblasts seeded on ruthenium-crosslinked lung ECM-derived hydrogels showed myofibroblastic differentiation with a loss of spindle-like morphology together with greater α-smooth muscle actin (α-SMA) expression, increased nuclear area and circularity without any decrease in the viability, compared with the fibroblasts seeded on the native lung-derived ECM hydrogels. In summary, ruthenium crosslinking of native ECM-derived hydrogels provides an exciting opportunity to alter the biomechanical properties of the ECM-derived hydrogels while maintaining the protein composition of the ECM to study the influence of mechanics during fibrotic lung diseases. STATEMENT OF SIGNIFICANCE: Fibrotic lung disease is characterized by changes in composition and excessive deposition of extracellular matrix (ECM). ECM fibre structure also changes due to crosslinking, which results in mechanical changes. Separating the changes in composition and mechanical properties has been difficult to date. In this study, we developed an in vitro model that allows alteration of the mechanical changes alone by applying fibre crosslinking in native lung ECM-derived hydrogels. Characterisations of the crosslinked hydrogels indicated the model mimicked mechanical properties of fibrotic lung tissue and reflected altered fibre organisation. This ECM-based fibrosis model provides a method to preserve the native protein composition while altering the mechanical properties providing an important tool not only for lung but also other organ fibrosis

Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites

BackgroundLingguizhugan decoction is a traditional Chinese medicine prescription that has been used to improve non-alcoholic fatty liver disease and its progressive form, non-alcoholic steatohepatitis (NASH). However, the anti-NASH effects and underlying mechanisms of Lingguizhugan decoction remain unclear.MethodsMale Sprague-Dawley rats were fed a methionine- and choline-deficient (MCD) diet to induce NASH, and then given Lingguizhugan decoction orally for four weeks. NASH indexes were evaluated by histopathological analysis and biochemical parameters including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver triglycerides (TG), etc. Fecal samples of rats were subjected to profile the changes of gut microbiota and metabolites using 16S rRNA sequencing and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS). Bioinformatics was used to identify Lingguizhugan decoction reversed candidates, and Spearman’s correlation analysis was performed to uncover the relationship among gut microbiota, fecal metabolites, and NASH indexes.ResultsFour-week Lingguizhugan decoction treatment ameliorated MCD diet-induced NASH features, as evidenced by improved hepatic steatosis and inflammation, as well as decreased serum AST and ALT levels. Besides, Lingguizhugan decoction partially restored the changes in gut microbial community composition in NASH rats. Meanwhile, the relative abundance of 26 genera was significantly changed in NASH rats, and 11 genera (such as odoribacter, Ruminococcus_1, Ruminococcaceae_UCG-004, etc.) were identified as significantly reversed by Lingguizhugan decoction. Additionally, a total of 99 metabolites were significantly altered in NASH rats, and 57 metabolites (such as TDCA, Glutamic acid, Isocaproic acid, etc.) enriched in different pathways were reversed by Lingguizhugan decoction. Furthermore, Spearman’s correlation analyses revealed that most of the 57 metabolites were significantly correlated with 11 genera and NASH indexes.ConclusionLingguizhugan decoction may exert protective effects on NASH partially by modulating gut microbiota and correlated metabolites

Effects of Astragalus Polysaccharides on Associated Immune Cells and Cytokines in Immunosuppressive Dogs

AbstractThe aim of this study was to determine the effects of Astragalus Polysaccharide (APS) on associated Immunity Cells and Cytokines in the immunosuppressive dogs and its dose-effect correlation. One hundred two-month-old male Chinese Countryside Dogs were randomly assigned to five groups: Control group (CG), immunosuppressive group (IG), APS low dose group (50mg/kg, LDG), APS median dose group (100mg/kg, MDG), and APS high dose group (200mg/kg, HDG), each group with twenty animals. After successfully established the dexamethasone-induced immunosuppressive models, with intravenous administer the CG and IG groups were daily dosed with saline, and the other three groups were daily dosed with APS for 7 days. On day 4 and 11 venous blood samples were collected and analyzed to determine the percentages of peripheral blood ANAE+ T lymphocytes, CD4+, CD8+ cells and CD4+/CD8+ ratio; the phagocytic index and percentage of the peritoneal macrophages; and the contents of INF-γ and IL-2. After 7 days administration, the measured parameters as described above in three treated groups increased significantly (P<0.05). Our findings show that the dosage of 200mg/kg APS can significantly enhance the cellular immune level of the immunosuppressive dogs. This study has provided evidence and basis for Astragalus polysaccharides development as companion animal health products as well as for its clinical application

Differential roles for lysyl oxidase (like), family members in chronic obstructive pulmonary disease; from gene and protein expression to function:from gene and protein expression to function

Chronic obstructive pulmonary disease (COPD) is characterized by long-term airflow obstruction with cigarette smoke as a key risk factor. Extracellular matrix (ECM) alterations in COPD may lead to small airway wall fibrosis. Altered collagen cross-linking, potentially mediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1-4), orchestrates disturbed ECM homeostasis. In this study, we investigated the effects of smoking status and presence and severity of COPD on LOs gene and protein expression in the airways and the impact of LOs inhibition on airway contraction in an ex vivo mouse model. We used gene expression data from bronchial brushings, airway smooth muscle (ASM) cells in vitro and immunohistochemistry in lung tissue to assess smoke- and COPD-associated differences in LOs gene and protein expression in the small airways. We found higher LOX expression in current- compared to ex-smokers and higher LOXL1 expression in COPD compared to non-COPD patients. LOX and LOXL2 expression were upregulated in COPD ASM cells treated with cigarette smoke extract. LOXL1 and LOXL2 protein levels were higher in small airways from current- compared to non-smokers. In COPD patients, higher LOXL1 and lower LOX protein levels were observed, but no differences for LOXL2, LOXL3, and LOXL4 protein were detected in small airways. Inhibiting LOs activity increased airway contraction in murine lung slices. COPD-associated changes in LOs, in particular LOX and LOXL1, may be related to smoking and contribute to impaired airway function, providing potential novel targets for preventing or treating small airways changes in COPD