Sphingosine kinase 1 regulates HMGB1 translocation by directly interacting with calcium/calmodulin protein kinase II-δ in sepsis-associated liver injury

Previously, we confirmed that sphingosine kinase 1 (SphK1) inhibition improves sepsis-associated liver injury. High-mobility group box 1 (HMGB1) translocation participates in the development of acute liver failure. However, little information is available on the association between SphK1 and HMGB1 translocation during sepsis-associated liver injury. In the present study, we aimed to explore the effect of SphK1 inhibition on HMGB1 translocation and the underlying mechanism during sepsis-associated liver injury. Primary Kupffer cells and hepatocytes were isolated from SD rats. The rat model of sepsis-associated liver damage was induced by intraperitoneal injection with lipopolysaccharide (LPS). We confirmed that Kupffer cells were the cells primarily secreting HMGB1 in the liver after LPS stimulation. LPS-mediated HMGB1 expression, intracellular translocation, and acetylation were dramatically decreased by SphK1 inhibition. Nuclear histone deacetyltransferase 4 (HDAC4) translocation and E1A-associated protein p300 (p300) expression regulating the acetylation of HMGB1 were also suppressed by SphK1 inhibition. HDAC4 intracellular translocation has been reported to be controlled by the phosphorylation of HDAC4. The phosphorylation of HDAC4 is modulated by CaMKII-δ. However, these changes were completely blocked by SphK1 inhibition. Additionally, by performing coimmunoprecipitation and pull-down assays, we revealed that SphK1 can directly interact with CaMKII-δ. The colocalization of SphK1 and CaMKII-δ was verified in human liver tissues with sepsis-associated liver injury. In conclusion, SphK1 inhibition diminishes HMGB1 intracellular translocation in sepsis-associated liver injury. The mechanism is associated with the direct interaction of SphK1 and CaMKII-δ.Subject terms: Hepatotoxicity, Sepsis     

互花米草、狐米草和大绳草茎秆的比较解剖观察

互花米草、狐米草和大绳草的表皮均由长细胞、短细胞(栓质细胞和硅质细胞)、盐腺和气孔器组成。它们成纵行交互排列。盐腺的结构与大米草相似,但三个种的盐腺和气孔器的数目不同,尤其以大绳草最多。它们的内部结构是由气道、不同大小的维管束、基本组织以及厚壁组织组成。然而,维管束的数目及厚壁组织的发育各不相同。狐米草和大绳草有高度木质化的厚壁组织细胞,而互花米草的厚壁组织木质化较弱。大绳草的维管束多于其他两种。     

Improved predictive test for MEN2, using flanking dinucleotide repeats and RFLPs.

Gene(s) for the autosomal dominant endocrine cancer syndromes, multiple endocrine neoplasia type 2A (MEN2A), multiple endocrine neoplasia type 2B (MEN2B), and familial medullary thyroid carcinoma (MTC1) all map to the pericentromeric region of chromosome 10. Predictive testing for the inheritance of mutant alleles in individuals at risk for these disorders has been limited by the availability of highly informative and closely linked flanking markers. We describe the development of eight new markers, including two PCR-based dinucleotide repeat polymorphisms and six RFLPs that flank the disease loci. One of the dinucleotide repeat markers (sJRH-1) derives from the RBP3 locus on 10q11.2 and has a PIC of .88. The other dinucleotide repeat (sTCL-1) defines a new locus, D10S176, that maps by in situ hybridization to 10p11.2 and has a PIC of .68. We have constructed a new genetic linkage map of the pericentromeric region of chromosome 10, on the basis of 13 polymorphisms at six loci, which places the MEN2A locus between the dinucleotide repeat markers, with odds of 5,750:1 over the next most likely position. Using this set of markers, predictive genetic testing of 130 at-risk individuals from six families segregating MEN2A revealed that 95% were jointly informative with flanking markers, representing a significant improvement in genetic testing capabilities.     

Taxonomy, biology and abundance of icefishes, or noodlefishes (Salangidae), in the Yellow River estuary of the Bohai Sea, China

Four species of icefishes were sampled in the Yellow River estuary of the Bohai Sea from April 1984 to April 1985 and from February 1988 to June 1989. Morphological analysis showed that they belonged to three subfamilies of Salangidae: one species from Protosalangicae, Protosalanx chinensis ; two species from Salanginae, Salanx ariakensis and Salanx prognathus ; and one species, Neosalanx andersoni , from Salangichthyinae, a new subfamily. External morphological characteristics, population composition, growth, maturity, food habits, longevity, fecundity, abundance and distribution of these icefishes are described. Based on these analyses, a clear outline of taxonomy, zoogeography aod biology of icefishes in the Yellow River estuary of the Bohai Sea was established.     

训练与β－内啡肽对急性运动反应关系的研究

用放射免疫法测定训练和非训练大鼠运动前、运动到５０％耐力时间（Ｔ１／２）和衰竭时丘脑下部和血浆β－内啡肽（β－ＥＰ）的含量,探索了训练与β－ＥＰ对急性运动反应的关系。结果表明：训练组大鼠丘脑下部β－ＥＰ含量在运动到Ｔ１／２和衰竭时分别较安静时提高了４％和１５％;对照组大鼠在Ｔ１／２时,β－ＥＰ的变化趋势同训练组,以后随运动生理负荷的增强而迅速降低,衰竭时较Ｔ１／２时降低了２６％,较训练组降低了３２％（Ｐ＜０．０５）。训练组大鼠血浆β－ＥＰ含量随运动开始迅速上升,Ｔ１／２时较运动前增加了５．７倍（Ｐ＜０．０１）,以后上升的幅度减小;非训练组大鼠血浆β－ＥＰ也随运动开始迅速提高（Ｐ＜０．０１）,Ｔ１／２后趋于稳定,在Ｔ１／２和衰竭时分别比训练组低２２％和２６％。表明非训练组大鼠丘脑下部β－Ｅｐ对急性运动呈明显的双相变化,训练提高了大鼠丘脑下部和血浆β－ＥＰ对衰竭运动的反应。     

津白_3侏儒小鼠垂体前叶生长激素细胞的免疫细胞化学研究

津白_３侏儒小鼠（ｄＷ~ｔ）是１９８２年从津白_３纯系小鼠（ＴＡ_３）中发现,进而培育成侏的变种。本实验应用免疫细胞化学技术,对ｄｗ￣ｔ小鼠垂体前叶生长激素（ＧＨ）细胞进行观察,并根据体视学原理进行定量分析,以探讨ｄｗ~ｔ小鼠是否存在垂体发育缺陷。实验结果显示,ｄｗ~ｔ小鼠ＧＨ细胞的体积密度（Ｖｖ）和数密度（Ｎｖ）值均低于正常对照组,Ｐ＜０．０１～０．００１。表明ｄｗ~ｔ小鼠由于垂体前叶ＧＨ细胞数量减少,导致ＧＨ分泌不足,从而形成侏儒。     

Reduced Application of Nitrogen Fertilizer Affects the Carbon Metabolism of Leaves and Maintains the Number of Flowers in Coreopsis tinctoria

This study examined the effects of nitrogen (N) fertilizer reduction on the carbon (C) metabolism and yield of Coreopsis tinctoria. A two-year (2020–2021) hydroponic experiment was conducted in accordance with a randomized complete group design with five N levels [0.875 mM Ca(NO₃)₂ (N1), 1.750 mM Ca(NO₃)₂ (N2), 3.500 mM Ca(NO₃)₂ (N3), 7.000 mM Ca(NO₃)₂ (N4), and 14.000 mM Ca(NO₃)₂ (N5)] and three replications. The results showed that low N significantly affected the functional leaf weight, C metabolism, and flower bud (or flower) numbers of C. tinctoria at harvest. Lower-N levels, especially those of the N2 treatment, significantly increased Rubisco, sucrose synthase (SS), sucrose phosphate synthase (SPS), soluble acid invertase (SAI), glucose 6-phosphate dehydrogenase (G6PDH), and 6-phosphogluconate dehydrogenase (6PGDH) activity and maintained the flower number of C. tinctoria. In addition, the balance of carbohydrates (sucrose, starch, glucose, and fructose) and ATP contents was more efficiently maintained under relatively low-N levels. These findings might suggest that reduced application of N fertilizer affects the C metabolism of leaves and maintains the number of flowers in Coreopsis tinctoria. Applying relatively low-N fertilizer levels is also a promising cultivation strategy for C. tinctoria.

     

Retraction Note: miR-195-5p/NOTCH2-mediated EMT modulates IL-4 secretion in colorectal cancer to affect M2-like TAM polarization

Background

Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising.

Methods

Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes.

Results

An integrated diagnostic model called “Combined method” was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.