Loss of PDZK1 expression activates PI3K/AKT signaling via PTEN phosphorylation in gastric cancer

Phosphorylation of PTEN plays an important role in carcinogenesis and progression of gastric cancer. However, the underlying mechanism of PTEN phosphorylation regulation remains largely elusive. In the present study, PDZK1 was identified as a novel binding protein of PTEN by association of PTEN through its carboxyl terminus and PDZ domains of PDZK1. By direct interaction with PTEN, PDZK1 inhibited the phosphorylation of PTEN at S380/T382/T383 cluster and further enhanced the capacity of PTEN to suppress PI3K/AKT activation. PDZK1 suppressed gastric cancer cell proliferation by diminishing PI3K/AKT activation via inhibition of PTEN phosphorylation in vitro and in vivo. The expression of PDZK1 was frequently downregulated in gastric cancer specimens and correlated with progression and poor prognosis of gastric cancer patients. Downregulation of PDZK1 was associated with PTEN inactivation, AKT signaling and cell proliferation activation in clinical specimens. Thus, low levels of PDZK1 in gastric cancer specimens lead to increase proliferation of gastric cancer cells via phosphorylation of PTEN at the S380/T382/T383 cluster and constitutively activation of PI3K/AKT signaling, which results in poor prognosis of gastric cancer patients

Breast cancer-derived K172N, D301V mutations abolish Na+/H+ exchanger regulatory factor 1 inhibition of platelet-derived growth factor receptor signaling

AbstractNa+/H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein known to interact with a number of cancer-related proteins. nherf1 Mutations (K172N and D301V) were recently identified in breast cancer cells. To investigate the functional properties of NHERF1, wild-type and cancer-derived nherf1 mutations were stably expressed in SKMES-1 cells respectively. NHERF1-wt overexpression suppressed the cellular malignant phenotypes, including proliferation, migration, and invasion. nherf1 Mutations (K172N and D301V) caused complete or partial loss of NHERF1 functions by affecting the PTEN/NHERF1/PDGFRβ complex formation, inactivating NHERF1 inhibition of PDGF-induced AKT and ERK activation, and attenuating the tumor-suppressor effects of NHERF1-wt. These results further demonstrated the functional consequences of breast cancer-derived nherf1 mutations (K172N and D301V), and suggested the causal role of NHERF1 in tumor development and progression

Comparative analysis of the efficacies of probiotic supplementation and glucose-lowering drugs for the treatment of type 2 diabetes: A systematic review and meta-analysis

The aim of this systematic review and meta-analysis was to evaluate the effects of probiotics and glucose-lowering drugs (thiazolidinedione [TZD], glucagon-like pep-tide-1 receptor agonists [GLP-1 RA], dipeptidyl peptidase IV inhibitors, and sodium glucose co-transporter 2 inhibitors [SGLT-2i]) in patients with type 2 diabetes from randomized con-trolled trials (RCTs). The PubMed, Web of science, Embase, and Cochrane Library databases were searched on the treatment effects of probiotics and glucose-lowering drugs on glycemia, lipids, and blood pressure metabolism published between Jan 2015 and April 2021. We performed meta-analyses using the random-effects model. We included 25 RCTs (2,843 participants). Overall, GLP-1RA, SGLT-2i, and TZD significantly reduce fasting blood sugar (FBS) and glycated hemoglobin (HbA1c), whereas GLP-1 RA increased the risk of hypoglycaemia. Multispecies probiotics decrease FBS, total cholesterol (TC), and systolic and diastolic blood pressure (SBP, DBP). Moreover, subgroup analyses indicated that participants aged >55 years, BMI ≥30 kg/m2, longer duration of intervention, and subjects from Eastern countries, showed significantly higher reduction in FBS and HbA1c, TC, TG and SBP. This meta-analysis revealed that including multiple probiotic rather than glucose-lowering drugs might be more beneficial regarding T2D prevention who suffering from simultaneously hyperglycemia, hypercholesterolemia, and hypertension

Plastic bag as horizontal photobioreactor on rocking platform driven by water power for culture of alkalihalophilic cyanobacterium

Abstract Background Mixing in traditional algae culture system consumes intensive electricity. This should be replaced by nature force to reduce energy cost and, more importantly, to realize positive energy balance of algal biofuel production. This study aims to develop a horizontal photobioreactor, in which mixing can be provided with rocking movement driven by nature force. Results Simple boxes were used as small-scale horizontal photobioreactors on a rocking platform for culture of alkalihalophilic Euhalothece sp. ZM001. There was no CO2 gas bubbling since 1.0 M NaHCO3 supplied sufficient inorganic carbon in it. Effect of culture depth, rocking cycle, and light intensity to algal biomass production, pH change, and DO accumulation were investigated in this system. Biomass concentration of 2.73 g/L was achieved in culture with 2.5 cm depth, and maximum productivity of 17.06 g/m2/day was obtained in culture with 10 cm depth. k L a in PBR with different culture depths and rocking cycles was measured, and it was from 0.57 to 33.49 h−1, showing great variation. To test this system at large scale, a plastic bag with a surface area of 1 m2 was placed on a rocking platform driven by water power, and it resulted in a biomass concentration of 1.88 g/L. Conclusion These results proved feasibility of a novel photobioreactor system driven by nature force, as well as low cost of manufacturing, and easy scaling-up

Genome-Wide Transcriptome Analysis Reveals the Comprehensive Response of Two Susceptible Poplar Sections to Marssonina brunnea Infection

Marssonina leaf spot disease of poplar (MLDP), caused by the hemibiotrophic pathogen Marssonina brunnea, frequently results in damage to many poplar species. In nature, two formae speciales of M. brunnea exist that are susceptible to different poplar subgenera. Marssonina brunnea f. sp. monogermtubi infects poplar hosts from Populus sect. Aigeiros (Aig), while M. brunnea f. sp. multigermtubi always infects poplar hosts from Populus sect. Leuce Duby (Leu). Based on the fungal penetration structures, a comprehensive transcriptomic approach was used to investigate the gene expression patterns of these two poplar subgenera at three crucial infection stages. MLDP significantly altered the expression patterns of many genes involved in mitogen activated protein kinase (MAPKs) and calcium signaling, transcription factors, primary and secondary metabolism, and other processes in both poplar subgenera. However, major differences in gene expression were also observed between the two poplar subgenera. Aig was most responsive at the initial infection stage, while Leu largely interacted with M. brunnea at the necrotrophic phase. Furthermore, the differentially expressed genes (DEGs) involved in pathways related to biotic stress also differed substantially between the two poplar subgenera. Further analysis indicated that the genes involved in cell wall metabolism and phenylpropanoid metabolism were differentially expressed in the progression of the disease. By examining the expression patterns of genes related to the defense against disease, we found that several genes annotated with causing hypersensitive cell death were upregulated at the necrotrophic phase of MLDP, inferring that plant immune response potentially happened at this infection stage. The present research elucidated the potential molecular differences between the two susceptible interaction systems in MLDP and provided novel insight into the temporal regulation of genes during the susceptible response. To the best of our knowledge, this study also constitutes the first to reveal the molecular mechanisms of poplar in response to the transition of hemibiotrophic fungal pathogens from the biotrophic phase to the necrotrophic phase

Development of standard fuel models in boreal forests of Northeast China through calibration and validation.

Understanding the fire prediction capabilities of fuel models is vital to forest fire management. Various fuel models have been developed in the Great Xing'an Mountains in Northeast China. However, the performances of these fuel models have not been tested for historical occurrences of wildfires. Consequently, the applicability of these models requires further investigation. Thus, this paper aims to develop standard fuel models. Seven vegetation types were combined into three fuel models according to potential fire behaviors which were clustered using Euclidean distance algorithms. Fuel model parameter sensitivity was analyzed by the Morris screening method. Results showed that the fuel model parameters 1-hour time-lag loading, dead heat content, live heat content, 1-hour time-lag SAV(Surface Area-to-Volume), live shrub SAV, and fuel bed depth have high sensitivity. Two main sensitive fuel parameters: 1-hour time-lag loading and fuel bed depth, were determined as adjustment parameters because of their high spatio-temporal variability. The FARSITE model was then used to test the fire prediction capabilities of the combined fuel models (uncalibrated fuel models). FARSITE was shown to yield an unrealistic prediction of the historical fire. However, the calibrated fuel models significantly improved the capabilities of the fuel models to predict the actual fire with an accuracy of 89%. Validation results also showed that the model can estimate the actual fires with an accuracy exceeding 56% by using the calibrated fuel models. Therefore, these fuel models can be efficiently used to calculate fire behaviors, which can be helpful in forest fire management

Implementation of Fully Self-Aligned Homojunction Double-Gate a-IGZO TFTs

A simple method of fabricating fully self-aligned double-gate (SADG) homojunction a-IGZO TFTs is proposed and experimentally demonstrated for the first time. The self-alignment between the bottom-and top-gates is realized with one backside-illuminated photolithographic step; and that between the source/drain regions and the two gates is formed by both argon plasma treatment and hydrogen doping. The resulting overlap between the gate and source/drain regions is about 0.3 m. Excellent symmetry between bidirectional transfer characteristics in the fabricated SADG TFTs is observed. Moreover, the dynamic threshold voltage operation is well demonstrated, and the driving capability, electrical stress effects under tied and separate gate biases are investigated

Descriptions of the five historical fire patches.

<p>Descriptions of the five historical fire patches.</p

Calibration results of fire size between uncalibrated and calibrated fuel models.

<p>Calibration results of fire size between uncalibrated and calibrated fuel models.</p