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GH3536 and GH4169 nickel-based superalloys are widely used in aerospace engines and other hot-end components. In this paper，GH3536 and GH4169 alloy samples were fabricated by optimizing the process parameters using selective laser melting（SLM），the defect characteristics and microstructure of two alloys，as well as the effects of different homogenization temperatures and holding times on microstructure evolution，average grain size，and properties of two alloys were studied. The defect characteristics and microstructure were investigated by OM，SEM，and EDS, et al. The Vickers hardness meter was used to test the alloy’s microhardness. The results indicate that the as-built GH3536 alloy exhibits more defects，including pores，cracks，and lack of fusion， while only pores are present in as-built GH4169 alloy. The melt pool of alloy is eliminated by homogenization treatment，and the grains grow into equiaxed grains. M23C6 are found to distribute within grain boundaries and grain interiors of GH3536 alloy，while NbC are found to distribute within grain boundaries and grain interiors of GH4169 alloy，and the amount of precipitates is significantly reduced with the increase of homogenization temperature. The average grain size of GH3536 alloy is increased by 106.8% from 48.5 μm at 1130 ℃/1 h to 100.9 μm at 1250 ℃/4 h . The grain size of GH4169 alloy is increased by 53.3% from 57 μm at 1080 ℃/1 h to 87.4 μm at 1200 ℃/4 h.The homogenization treatment of GH3536 alloy and GH4169 alloy results in a significant decrease in microhardness of the former，from 262HV to 180-190HV，while the latter shows a significant increase，from 313HV to 430-450HV.

Simple Summary: Inflammatory bowel disease (IBD) is characterized by mucous bloody stools, abdominal pain, and diarrhea. Once diagnosed with IBD, the patients often rely on medication for several years due to its incurability, and some may require surgical treatments. The pathogenesis of IBD is still unrevealed. It is believed to result from excessive immune and inflammatory responses to environmental factors in genetically susceptible individuals. The successful use of various biological agents (infliximab, adalimumab, and vitolizumab) has also confirmed the role of immune response in IBD. Mesenteric lymphatics penetrate the intestinal wall and form an immune complex with the intestine. Therefore, we aim to explore the role of mesenteric lymphatic immunity in IBD. We observed that the proportion of mesenteric lymphatic B (MLB) cells increased in IBD rats. The adoptive transfer of MLB cells aggravated IBD in the receipt rats, accompanied by changes in intestinal T cell number and function. Additionally, we identified the CXCR5-CXCL13 axis as being involved in inducting the migration of MLB cells to the intestine, indicating that MLB cells play important roles in IBD. The pathogenesis of inflammatory bowel disease (IBD) is still unknown. Mesenteric lymphatics (MLs), which are closely related to the intestine in both anatomy and physiology, have been suggested to be involved in IBD. In the present study, we aim to investigate the effects of ML immune cells on IBD and explore the potential associated mechanisms. Acute colitis was induced in rats using dextran sulfate sodium salt (DSS). Mesenteric lymphangiogenesis, ML stenosis, and dilation were observed, with an increased proportion of MLB cells in DSS-induced colitis rats. The adoptive transfer of B cells isolated from ML (MLB) was employed to investigate their effects on colitis. MLB cells derived from DSS-induced colitis rats exhibited a higher propensity to migrate to the intestine. The proportion of colonic T cells was altered, along with the aggravated colitis induced by the adoptive transfer of MLB cells derived from DSS-induced colitis rats. RNA sequencing revealed increased Cxcr5 expression in MLB cells from colitis rats, while real-time PCR indicated an upregulation of its ligand Cxcl13 in the colon of colitis rats. These findings suggest that MLB cells may migrate to the intestine and aggravate colitis. In summary, colonic T cells respond to MLB cells from colitis rats, and MLB cells aggravate DSS-induced colitis via the CXCR5–CXCL13 axis. [ABSTRACT FROM AUTHOR]

Leucine, a branched-chain amino acid that must be supplied in the daily diet, plays an important role in controlling protein synthesis and regulating cell metabolism in various cell types. In pancreatic [beta] cells, leucine acutely stimulates insulin secretion by serving as both metabofic fuel and allosteric activator of glutamate dehydrogenase to enhance glutaminolysis. Leucine has also been shown to regulate gene transcription and protein synthesis in pancreatic islet [beta] cells via both mTOR-dependent and -independent pathways at physiological concentrations. Long-term treatment with leucine has been shown to improve insulin secretory dysfunction of human diabetic islets via upregulation of certain key metabolic genes. In vivo, leucine administration improves glycemic control in humans and rodents with type 2 diabetes. This review summarizes and discusses the recent findings regarding the effects of leucine metabolism on pancreatic [beta]-cell function. doi: 10.1111/j.1753-4887.2010.00282.x

FAM3A is a recently identified mitochondrial protein that stimulates pancreatic-duodenal homeobox 1 (PDX1) and insulin expressions by promoting ATP release in islet β cells. In this study, the role of intracellular ATP in FAM3A-induced PDX1 expression in pancreatic β cells was further examined. Acute FAM3A inhibition using siRNA transfection in mouse pancreatic islets significantly reduced PDX1 expression, impaired insulin secretion, and caused glucose intolerance in normal mice. In vitro , FAM3A overexpression elevated both intracellular and extracellular ATP contents and promoted PDX1 expression and insulin secretion. FAM3A-induced increase in cellular calcium (Ca2+) levels, PDX1 expression, and insulin secretion, while these were significantly repressed by inhibitors of P2 receptors or the L-type Ca2+ channels. FAM3A-induced PDX1 expression was abolished by a calmodulin inhibitor. Likewise, FAM3A-induced β-cell proliferation was also inhibited by a P2 receptor inhibitor and an L-type Ca2+ channels inhibitor. Both intracellular and extracellular ATP contributed to FAM3A-induced PDX1 expression, insulin secretion, and proliferation of pancreatic β cells. [ABSTRACT FROM AUTHOR]

FAM3B, also known as PANcreatic DERived factor (PANDER), promotes gluconeogenesis and lipogenesis in hepatocytes. However, the underlying mechanism(s) still remains largely unclear. This study determined the mechanism of PANDER‐induced FOXO1 activation in hepatocytes. In mouse livers and cultured hepatocytes, PANDER protein is located in both the cytoplasm and nucleus. Nuclear PANDER distribution was increased in the livers of obese mice. In cultured mouse and human hepatocytes, PANDER was co‐localized with FOXO1 in the nucleus. PANDER directly interacted with FOXO1 in mouse and human hepatocytes. PANDER overexpression enhanced PANDER‐FOXO1 interaction, and detained FOXO1 in the nucleus upon insulin stimulation in hepatocytes. With the increase in PANDER‐FOXO1 interaction, PANDER overexpression upregulated the expression of gluconeogenic genes and promoted gluconeogenesis in both human and mouse hepatocytes. Luciferase reporter assays further revealed that PANDER augmented the transcriptional activity of FOXO1 on gluconeogenic genes. Moreover, PANDER overexpression also interfered the binding of AS1842856, a specific FOXO1 inhibitor, with FOXO1, and impaired its inhibitory effects on gluconeogenic gene expression and gluconeogenesis in hepatocytes. siRNA mediated‐silencing of FOXO1 inhibited PANDER‐promoted gluconeogenic gene expression and glucose production in hepatocytes. In conclusion, PANDER protein is abundantly present in the nucleus, where it functions as a new co‐activator of FOXO1 to induce gluconeogenic gene expression in hepatocytes. [ABSTRACT FROM AUTHOR]

The incidence and mortality rate of cancer has been quickly increasing in the past decades. At present, cancer has become the leading cause of death worldwide. Most of the cancers cannot be effectively diagnosed at the early stage. Although there are multiple therapeutic treatments, including surgery, radiotherapy, chemotherapy, and targeted drugs, their effectiveness is still limited. The overall survival rate of malignant cancers is still low. It is necessary to further study the mechanisms for malignant cancers, and explore new biomarkers and targets that are more sensitive and effective for early diagnosis, treatment, and prognosis of cancers than traditional biomarkers and methods. Long non-coding RNAs (lncRNAs) are a class of RNA transcripts with a length greater than 200 nucleotides. Generally, lncRNAs are not capable of encoding proteins or peptides. LncRNAs exert diverse biological functions by regulating gene expressions and functions at transcriptional, translational, and post-translational levels. In the past decade, it has been demonstrated that the dysregulated lncRNA profile is widely involved in the pathogenesis of many diseases, including cancer, metabolic disorders, and cardiovascular diseases. In particular, lncRNAs have been revealed to play an important role in tumor growth and metastasis. Many lncRNAs have been shown to be potential biomarkers and targets for the diagnosis and treatment of cancers. This review aims to briefly discuss the latest findings regarding the roles and mechanisms of some important lncRNAs in the pathogenesis of certain malignant cancers, including lung, breast, liver, and colorectal cancers, as well as hematological malignancies and neuroblastoma. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is characterized by altered intestinal microbiota and intestinal immune disorder. Here we investigated the role of mesenteric lymph node (MLN) CD4 + T lymphocytes in NAFLD. In high fat diet (HFD)-fed mice, the percentage ratios of Th1 to Th2 cells and Th17 to Treg cells were imbalanced in MLNs. Co-culture assays showed MLN CD4 + T lymphocytes from HFD-fed mice tended to migrate to the liver and promoted hepatic inflammation. Adoptive transfer of MLN CD4 + T lymphocytes from NAFLD mice to HFD-fed mice resulted in higher transaminase, worse hepatic inflammation and lipid accumulation. Antibiotics and probiotics were administrated to regulate intestinal microbiota, and the restoration of MLN Th1/Th2 and Th17/Treg cells in alleviated NAFLD were found. In summary, MLNs CD4 + T subtype cells may involve in NAFLD, and the restoration of MLN CD4 + T subtype cells ratio by regulating intestinal bacteria could be the new strategies., (Copyright © 2019. Published by Elsevier Inc.)

Visceral adipose tissue (VAT) is related to nonalcoholic fatty liver disease (NAFLD). However, the role of mesenteric adipose tissue (MAT), part of the VAT, in NAFLD is unclear. In the present study, we monitored the liver and four depots of the VAT in high-fat diet (HFD)-feeding mice at multiple time points (4, 8, and 12 wk). The MAT had become inflamed by the eighth week of HFD feeding, earlier than other depots of VAT. Furthermore, MAT removal after 8 wk of HFD resulted in more severe steatosis and more foci of inflammation infiltration, as well as higher NAFLD activity scores. Consistent with these findings, the mRNA expression of proinflammatory cytokines and lipid anabolism genes was increased in the livers of inflamed MAT-removal mice. MAT removal also injured the intestinal barrier and promoted intestinal inflammation. The bacterial load translocated to the liver and circulating levels of lipopolysaccharide were also evaluated in inflamed MAT-removal mice. In a coculture experiment involving adipocytes and intestinal epithelial cells, mRNA expression of zonula occludens-1 (ZO-1), and occludin in CT-26 cells was upregulated and permeability of monolayer Caco-2 cells was elevated under stimulation from adipocytes or inflamed adipocytes. Taken together, these results demonstrated that MAT removal damaged the intestinal barrier and aggravated NAFLD and that MAT inflammation may be a compensatory response to protect the liver by maintaining the intestinal barrier. NEW & NOTEWORTHY The mesenteric adipose tissue (MAT) lies between the gut and liver and plays a critical role in hepatic metabolic diseases. In the present study, we found that the MAT was prone to inflammation in high-fat diet-fed mice. Removal of the inflamed MAT resulted in more hepatic inflammation, lipid accumulation, and decreased glucose tolerance. Furthermore, we showed that the MAT contributed to intestinal barrier integrity, thus clarifying why MAT removal aggravated nonalcoholic fatty liver disease.

Objective: To investigate the role of myosin light chain kinase (MLCK) in intestinal barrier function in a mouse model with nonalcoholic steatohepatitis (NASH)., Methods: The C57BL/6 mice were randomly divided into five groups including control group, nonalcoholic fatty liver (NAFL) group, NAFL administrated with MLCK inhibitor ML-7 group, nonalcoholic steatohepatitis (NASH) group, NASH administrated with ML-7 group. Plasma ALT and AST were tested. The degree of liver steatosis was assessed by hematoxylin-eosin staining on liver tissue sections.Intestinal mucosal tight junction was observed by electron microscope. The expression of MLCK on intestinal mucosa was detected by immunohistochemistry staining. The level of lipopolysaccharide (LPS) in portal vein was determined by enzyme linked immune sorbent assay (ELISA). The protein and mRNA expression of inflammatory cytokines in liver tissue were tested using ELISA and real-time PCR., Results: MLCK expression in intestinal mucosa was increased in NASH group compared with control group (P<0.01). The tight junctions of intestinal barrier were disrupted in NASH group and intercellular space was larger than control group [(26.60 ± 1.20) nm vs (14.90 ± 0.33) nm, P<0.05], which were improved after ML-7 administration [(14.9 0 ± 0.67) nm]. The LPS in portal vein was higher in NASH group than control group [(7.260 ± 3.184) U/L vs (2.962 ± 0.845) U/L, P<0.05], suggesting that the permeability of intestinal barrier was impaired, however the level of LPS was reduced by ML-7 [(3.772 ± 1.033) U/L, P<0.05]. ALT and AST in plasma, TNFα and IL-6 in liver tissue, the mRNA levels of TNFα and NF-κB in liver tissue were all elevated in NASH group compared with control group (all P<0.05), which were reduced by MLCK inhibitor ML-7., Conclusion: Epithelia MLCK probably plays a role in intestinal barrier impairment, which is critical to the pathogenesis of NASH.