Inhibitors of Phosphatidylinositol 3′-Kinases Promote Mitotic Cell Death in HeLa Cells

The phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in many biological processes, including cell cycle progression, cell growth, survival, actin rearrangement and migration, and intracellular vesicular transport. However, the involvement of the PI3K pathway in the regulation of mitotic cell death remains unclear. In this study, we treated HeLa cells with the PI3K inhibitors, 3-methyladenine (3-MA, as well as a widely used autophagy inhibitor) and wortmannin to examine their effects on cell fates using live cell imaging. Treatment with 3-MA decreased cell viability in a time- and dose-dependent manner and was associated with caspase-3 activation. Interestingly, 3-MA-induced cell death was not affected by RNA interference-mediated knockdown (KD) of beclin1 (an essential protein for autophagy) in HeLa cells, or by deletion of atg5 (an essential autophagy gene) in mouse embryonic fibroblasts (MEFs). These data indicate that cell death induced by 3-MA occurs independently of its ability to inhibit autophagy. The results from live cell imaging studies showed that the inhibition of PI3Ks increased the occurrence of lagging chromosomes and cell cycle arrest and cell death in prometaphase. Furthermore, PI3K inhibitors promoted nocodazole-induced mitotic cell death and reduced mitotic slippage. Overexpression of Akt (the downstream target of PI3K) antagonized PI3K inhibitor-induced mitotic cell death and promoted nocodazole-induced mitotic slippage. These results suggest a novel role for the PI3K pathway in regulating mitotic progression and preventing mitotic cell death and provide justification for the use of PI3K inhibitors in combination with anti-mitotic drugs to combat cancer

An integrated framework for multi-state driver monitoring using heterogeneous loss and attention-based feature decoupling

Multi-state driver monitoring is a key technique in building human-centric intelligent driving systems. This paper presents an integrated visual-based multi-state driver monitoring framework that incorporates head rotation, gaze, blinking, and yawning. To solve the challenge of head pose and gaze estimation, this paper proposes a unified network architecture that tackles these estimations as soft classification tasks. A feature decoupling module was developed to decouple the extracted features from different axis domains. Furthermore, a cascade cross-entropy was designed to restrict large deviations during the training phase, which was combined with the other features to form a heterogeneous loss function. In addition, gaze consistency was used to optimize its estimation, which also informed the model architecture design of the gaze estimation task. Finally, the proposed method was verified on several widely used benchmark datasets. Comprehensive experiments were conducted to evaluate the proposed method and the experimental results showed that the proposed method could achieve a state-of-the-art performance compared to other methods

Three-dimensional modeling and simulation of muscle tissue puncture process

Needle biopsy is an essential part of modern clinical medicine. The puncture accuracy and sampling success rate of puncture surgery can be effectively improved through virtual surgery. There are few three-dimensional puncture (3D) models, which have little significance for surgical guidance under complicated conditions and restrict the development of virtual surgery. In this paper, a 3D simulation of the muscle tissue puncture process is studied. Firstly, the mechanical properties of muscle tissue are measured. The Mooney-Rivlin (M-R) model is selected by considering the fitting accuracy and calculation speed. Subsequently, an accurate 3D dynamic puncture model is established. The failure criterion is used to define the breaking characteristics of the muscle, and the bilinear cohesion model defines the breaking process. Experiments with different puncture speeds are carried out through the built in vitro puncture platform. The experimental results are compared with the simulation results. The experimental and simulated reaction force curves are highly consistent, which verifies the accuracy of the model. Finally, the model under different parameters is studied. The simulation results of varying puncture depths and puncture speeds are analyzed. The 3D puncture model can provide more accurate model support for virtual surgery and help improve the success rate of puncture surgery

Performance Analysis of an integrated Semi-TransparentThin Film PV Vacuum Insulated Glazing

TNottingham University, Department of his paper is intended to design and develop a thermal model of an integrated semitransparent thin-film PV vacuum glazing with four layers of glass called PV VG-4L. Correspondence to: Hasila Jarimi, The design of the glazing involves integration between a thin-film PV glazing with a double vacuum glazing both manufactured independently , and an additional layer of selfcleaning coated glass. For the mathematical model, the energy balance equations were derived for the thin-film PV glass, the glass panes of the vacuum glazing and the edges of the internal and external glass surfaces facing indoors and outdoors respectively . The model was numerically solved in MATLAB. To evaluate the performance of the PV VG-4L, the prototype was manufactured and investigated at lab-scale and also under real conditions. At lab-scale, experiments were conducted at steady-state conditions using a TEC driven calibrated hot box at Sustainable Energy Research Lab, University of Nottingham, UK. Meanwhile, outdoors, the prototype was tested at a research house at the University of Nottingham, UK. The developed model was then validated against the experimental results by direct comparison on the trend of the experimental and theoretical curves obtained, and also by conducting error analysis using root mean squared percentage deviation RMSPD method. When tested using the calibrated hot box, by following closely the ISO 12567 standards, the average measured total U-value is 0.6 W/m2K. From the analysis, the computed RMSPD value for the glazing surface temperature and the U-value are 4.75 % and 0.96% respectively. The RMPSD computed for the glazing surface temperatures, electrical power generated under real conditions and U-value are 2.58 %, 1.4% and 6.86 % respectively. The theoretical and experimental results are concluded to be in good agreement. The thermal and electrical performance of a building retrofitted with and without PV VG-4L was examined and discussed. At building efficiency level, the PV VG-4L not only can produce power, but it also has high insulating properties. The promising U-value implies that the glazing’s range of potential applications can be improved depending on the energy needs and applications, which includes its use in BIPV solar façades PV curtain walling for commercial buildings, greenhouses, skylights and conservatorie

Analysis of the relationship between the gut microbiota enterotypes and colorectal adenoma

IntroductionThe essence of enterotypes is to stratify the entire human gut microbiota, and dysregulation of gut microbiota is closely related to the development of colorectal adenoma. Enterotypes may therefore be a useful target for the prevention of colorectal adenoma. However, the relationship between gut microbiota and colorectal adenoma has not been fully elucidated. In this study, we aimed to analyze the differences in gut microbiome composition between adenoma and control populations.MethodsWe recruited 31 patients with colorectal adenoma and 71 non-adenoma controls. Patient demographics, risk factors, fecal samples from each subject were collected and metagenomic sequencing was performed. LEfSe analysis was used to reveal differences in intestinal microbiome composition. Multiple logistic regression analysis was used to determine the association between enterotypes and colorectal adenoma.ResultsThe results showed that Prevotella enterotype (enterotype 4) is only present in adenoma group. Logistic regression analysis showed that Prevotella enterotype was an independent risk factor for colorectal adenoma.DiscussionThe Prevotella enterotype may increase the occurrence of colorectal adenoma through inflammatory association and interference with glucose and lipid metabolism in human body. In conclusion, the differences we observed between different enterotypes add a new potential factor to the development of colorectal adenoma

Magnetically-targetable outer-membrane vesicles for sonodynamic eradication of antibiotic-tolerant bacteria in bacterial meningitis

Treatment of acute bacterial meningitis is difficult due to the impermeability of the blood-brain barrier, greatly limiting the antibiotic concentrations that can be achieved in the brain. Escherichia coli grown in presence of iron-oxide magnetic nanoparticles secrete large amounts of magnetic outer-membrane vesicles (OMVs) in order to remove excess Fe from their cytoplasm. OMVs are fully biomimetic nanocarriers, but can be inflammatory. Here, non-inflammatory magnetic OMVs were prepared from an E. coli strain in which the synthesis of inflammatory lipid A acyltransferase was inhibited using CRISPR/Cas9 mediated gene knockout. OMVs were loaded with ceftriaxone (CRO) and meso-tetra-(4-carboxyphenyl)porphine (TCPP) and magnetically driven across the blood-brain barrier for sonodynamic treatment of bacterial meningitis. ROS-generation upon ultrasound application of CRO- and TCPP-loaded OMVs yielded similar ROS-generation as by TCPP in solution. In vitro, ROS-generation by CRO- and TCPP-loaded OMVs upon ultrasound application operated synergistically with CRO to kill a hard-to-kill, CRO-tolerant E. coli strain. In a mouse model of CRO-tolerant E. coli meningitis, CRO- and TCPP-loaded OMVs improved survival rates and clinical behavioral scores of infected mice after magnetic targeting and ultrasound application. Recurrence did not occur for at least two weeks after arresting treatment.</p

Effects of four types of natural bait on water quality, feeding, growth, and antioxidant enzyme activity of Monopterus albus in a recirculating aquaculture system

Monopterus albus is one of China’s renowned and superior aquaculture species, with its seedlings mainly sourced from wild capture. One of the bottlenecks in M. albus aquaculture is the high mortality rate and low feeding initiation rate from stocking wild fry to the initiation of feeding. In production, trash fish is commonly used to wean M. albus juveniles onto feeding. In this study, we introduced three other natural feeds, earthworms (EW), yellow mealworms (YMW), and fly maggots (FM), with frozen trash fish (TF) serving as the control group, to evaluate the effects of these four natural feeds on the survival rate, feeding initiation, antioxidant enzymes activity, and body composition of M. albus juveniles under recirculating water aquaculture conditions. The experiment comprised four treatments, each with three replicates. Each replicate consisted of stocking 150 M. albus juveniles weighing 10.02 ± 0.89 g in size, raised for 5 weeks. The survival rate of the YMW group was 73.33%–85.33%, which was significantly higher than that of the other three bait groups (p &lt; 0.05). The four bait groups showed no significant differences in final body weight and specific growth rate (SGR) (p &gt; 0.05). The EW group showed the highest final body weight, with an average SGR of 2.73, whereas the YMW group had an average SGR of 1.87. The average daily feeding amount was significantly higher in EW and YMW groups than in the other two groups (p &lt; 0.05). The percentage of feeding amount to fish weight in the EW group reached 7.3% in the fifth week. After 5 weeks of cultivation, NO2−-N content was significantly higher in the waters of the TF and EW groups than in the waters of the FM and YMW groups (p &lt; 0.05), there was no significant difference in TAN content among the treatment groups (p &gt; 0.05). Liver malondialdehyde content was significantly higher in the TF group than in the other bait groups (p &lt; 0.05). GSH-Px activity was significantly higher in the EW group than in the FM group and YMW group. No significant differences in SOD and CAT activity and T-AOC were observed among the bait groups (p &gt; 0.05). The increase in crude protein content was significantly higher in the TF group than in the FM group, but the increase in crude ash content was significantly lower in the TFgroup. In conclusion, Tenebrio molitor could potentially serve as one of the alternative feeds during the initial stages of M. albus juveniles stocking