Mathematical modeling of intracellular calcium in presence of receptor: a homeostatic model for endothelial cell

Biomechanics and Modeling in Mechanobiology - Calcium is a ubiquitous molecule and second messenger that regulates many cellular functions ranging from exocytosis to cell proliferation at different...     

EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation

Bladder cancer is a highly heterogeneous and aggressive malignancy with a poor prognosis. EGF/EGFR activation causes the detachment of SHC-binding protein 1 (SHCBP1) from SHC adapter protein 1 (SHC1), which subsequently translocates into the nucleus and promotes cancer development via multiple signaling pathways. However, the role of the EGF-SHCBP1 axis in bladder cancer progression remains unexplored. Herein, we report that SHCBP1 is upregulated in bladder cancer tissues and cells, with cytoplasmic or nuclear localization. Released SHCBP1 responds to EGF stimulation by translocating into the nucleus following Ser273 phosphorylation. Depletion of SHCBP1 reduces EGF-induced cell migration and invasiveness of bladder cancer cells. Mechanistically, SHCBP1 binds to RACGAP1 via its N-terminal domain of amino acids 1 ~ 428, and this interaction is enhanced following EGF treatment. Furthermore, SHCBP1 facilitates cell migration by inhibiting RACGAP-mediated GTP-RAC1 inactivation, whose activity is indispensable for cell movement. Collectively, we demonstrate that the EGF-SHCBP1-RACGAP1-RAC1 axis acts as a novel regulatory mechanism of bladder cancer progression, which offers a new clinical therapeutic strategy to combat bladder cancer.Subject terms: Bladder cancer, RHO signalling     

The hybrid enzymes from alpha-aspartyl dipeptidase and L-aspartase

With combinative functionalities as well as the improved activity and stability, the novel hybrid enzymes (HEs) from the heterogeneous enzymes of alpha-aspartyl dipeptidase (PepE, monomer) and l-aspartase (l-AspA, tetramer) were constructed successfully by gene random deletion strategy. The wild-type hybrid enzyme (WHE) and the evolved hybrid enzyme (EHE) were selected, respectively, upon the phenotype and the enzyme activity. The relative activity of the WHE tested was about 110% of the wild-type PepE and 26% of the wild-type l-AspA, whilst the activity of EHE was about 340% of the PepE and 87% of the l-AspA. In comparison to its individual wild-type enzymes, the EHE exhibited an improved thermostability, when examined at the enzyme concentration of 10(-7)mol/L, but the WHE showed a reduced thermostability. The activity of the EHE was about 3-fold compared to that of the WHE. The current results give a good example that the hybridization of enzymes could be attained between the monomer and multimer enzymes. In addition, they also indicate that construction hybrid enzyme from evolved enzymes is feasible.     

乌鲁木齐河源区高寒冰缘植被的生态特征研究

对乌鲁木齐河源区高寒冰缘植被进行了调查和生态环境分析。研究了高寒冰缘植物对寒区环境在形态结构和繁殖方式等方面的适应特征及其生态对策,在该区域垂直带谱中,植被包括了两个垂直带;高山草甸和高山垫状植被。主要植物群系有：苔草群系、蒿草群系、早熟禾群系、四蕊山莓草系、高山红景天群系、族生柔籽草群系、珠芽蓼群系等７个,共包括２７类植物群（群丛）此外,在高山流石堆上具有有牌演替早期阶段的高山植物群聚。决定该区     

Inverted U-Shaped Relationship between Central Venous Pressure and Intra-Abdominal Pressure in the Early Phase of Severe Acute Pancreatitis: A Retrospective Study

Objective

Many studies have indicated that intra-abdominal pressure (IAP) is positively correlated with central venous pressure (CVP) in severe cases. However, although elevated IAP is common in patients with severe acute pancreatitis (SAP), its relationship with CVP remains unclear. Our study aimed to investigate the association of IAP with CVP in early-phase SAP patients.

Methods

In total, 116 SAP patients were included in this retrospective study. On the first day of hospitalization, blood samples were collected for biochemical examination and cytokine concentration monitoring. Additionally, a urinary catheter and right subclavian vein catheter were inserted for IAP and CVP measurement, respectively. Other routine clinical data were also recorded.

Results

Within 24 hours after hospitalization, CVP fluctuated and increased with increasing IAP up to 15.7 mmHg (P = 0.054) but decreased with increasing IAP when the IAP was > 15.7 mmHg (P < 0.001). After adjusting for abdominal perfusion pressure (APP) and mean arterial pressure (MAP), a similar distribution was observed. An inverted U-shaped trend between IAP and CVP was also present in the groups classified according to the patient’s sex, local complications, ascites, and serum amylase levels.

Conclusions

CVP and IAP have an inverted U-shaped relationship, with a peak at an IAP of 15.7 mmHg in the early phase of SAP. After this peak, CVP decreases as IAP increases. These results have crucial implications for clinical fluid resuscitation in SAP patients. In particular, because one CVP value might be correlated with different IAP values in patients with the same CVP, the volume of fluid needed might be different.     

Novel Oxaliplatin Derivatives with 1‐(Substituted Benzyl)azetidine‐3,3‐dicarboxylate Anions. Synthesis,Cytotoxicity, and Interaction with DNA

A series of oxaliplatin derivatives with (1R,2R)‐N¹‐alkyl‐1,2‐cyclohexane‐1,2‐diamine (alkyl=Bu or ⁱPr) as carrier ligands and 1‐(methoxy‐ or methyl‐substituted benzyl)azetidine‐3,3‐dicarboxylate anions as leaving groups were synthesized and spectrally characterized. Generally, Complexes 10 – 15 with an ⁱPr substituent at N(1) showed higher activities in vitro than carboplatin against MCF‐7 human breast carcinoma and A549 human non‐small‐cell lung cell lines, although they were less potent than oxaliplatin. The typical complex 14 exhibited cytotoxicity superior to that of carboplatin and comparable to that of oxaliplatin against two selected tumor cell lines. Additionally, agarose gel electrophoresis was applied to investigate the DNA‐cleavage ability of complex 14 , which demonstrated that it has a different mode of DNA distortion from that of oxaliplatin.     

Taxonomic description of Pseudomonas rhizovicinus sp. nov., isolated from the rhizosphere of a desert shrub Haloxylon ammodendron

A Gram-negative aerobic bacterium, strain M30-35 ^T, was isolated from the rhizosphere of Haloxylon ammodendron in Tengger desert, Gansu province, northwest China. Our previous research indicated that strain M30-35 ^T can promote the growth of ryegrass (Lolium perenne L.). In this study, strain M30-35 ^T was subjected to a polyphasic taxonomic study. Phylogenetic analysis of the 16S rRNA gene and two other housekeeping genes (gyrB, rpoD) showed that strain M30-35 ^T is a member of Pseudomonas anguilliseptica group. The average nucleotide identity (ANI) scores for strains KMM 3042 ^T and FR1439^T were 76.5% and 83.7%, respectively, and DNA-DNA hybridization (DDH) were 21.6% and 26.6%, respectively, and the rates were less than the threshold range for species determination. The dominant cellular fatty acids of strain M30-35 ^T were C_16:0 (22.7%), summed feature 3 (C_16:1ω7c and/or C_16:1ω6c; 18.5%), summed feature 8 (C_18:1ω7c and/or C_18:1ω6c; 23.1%). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phospholipid and aminophospholipid and the predominant respiratory quinone was ubiquinone (Q9). On the basis of above data, it can be concluded that strain M30-35 ^T represents a novel species in the genus Pseudomonas, for which the name Pseudomonas rhizovicinus sp. nov. is proposed. The type strain is M30-35 ^T (=?MCCC 1K03247^T?=?KCTC 52664 ^T).

     

Melatonin inhibiting the survival of human gastric cancer cells under ER stress involving autophagy and Ras-Raf-MAPK signalling

Melatonin exhibits antitumour activities in the treatment of many human cancers. In the present study, we aimed to improve the therapeutic potential of melatonin in gastric cancer. Our results confirmed that melatonin dose-dependently suppressed the proliferation and necrosis, and increased G0/G1 phase arrest, apoptosis, autophagy and endoplasmic reticulum (ER) stress. The Ras-Raf-MAPK signalling pathway was activated in cells after melatonin treatment. RNA-seq was performed and GSEA analysis further confirmed that many down-regulated genes in melatonin-treated cells were associated with proliferation. However, GSEA analysis also indicated that many pathways related to metastasis were increased after melatonin treatment. Subsequently, combinatorial treatment was conducted to further investigate the therapeutic outcomes of melatonin. A combination of melatonin and thapsigargin increased the apoptotic rate and G0/G1 cell cycle arrest when compared to treatment with melatonin alone. Melatonin in combination with thapsigargin triggered the increased expression of Bip, LC3-II, phospho-Erk1/2 and phospho-p38 MAPK. In addition, STF-083010, an IRE1a inhibitor, further exacerbated the decrease in survival rate induced by combinatorial treatment with melatonin and thapsigargin. Collectively, melatonin was effective in gastric cancer treatment by modifying ER stress.