No abstract

Hyperglycemia is an important factor for chemoresistance of hepatocellular carcinoma patients with diabetes to therapeutics. In the present study, a series of selenadiazole derivatives have been rationally designed, synthesized, and found be able to antagonize drug resistance in HepG2 cells to doxorubicin (DOX) under simulated diabetes conditions. Hyperglycemia could promote the cell proliferation through upregulation of ERK and AKT phosphorylation. However, the synthetic selenadiazole derivatives effectively potentiated the cellular uptake of DOX and enhanced the antiproliferative activity of DOX on HepG2 cells by induction of apoptosis, via regulation of ROS-mediated AMPK activation, inhibition of mTORC1, and an increase in DNA damage. The selenadiazole derivatives that possess an increased lipophilicity could enhance the cellular uptake and anticancer efficacy of DOX. Taken together, this study provides a rational design strategy of selenadiazole derivatives to overcome hyperglycemia-induced drug resistance.

Due to use of different parametric models for establishing species sensitivity distributions (SSDs), comparison of water quality criteria (WQC) for metals of the same group or period in the periodic table is uncertain and results can be biased. To address this inadequacy, a new probabilistic model, based on non-parametric kernel density estimation was developed and optimal bandwidths and testing methods are proposed. Zinc (Zn), cadmium (Cd), and mercury (Hg) of group IIB of the periodic table are widespread in aquatic environments, mostly at small concentrations, but can exert detrimental effects on aquatic life and human health. With these metals as target compounds, the non-parametric kernel density estimation method and several conventional parametric density estimation methods were used to derive acute WQC of metals for protection of aquatic species in China that were compared and contrasted with WQC for other jurisdictions. HC5 values for protection of different types of species were derived for three metals by use of non-parametric kernel density estimation. The newly developed probabilistic model was superior to conventional parametric density estimations for constructing SSDs and for deriving WQC for these metals. HC5 values for the three metals were inversely proportional to atomic number, which means that the heavier atoms were more potent toxicants. The proposed method provides a novel alternative approach for developing SSDs that could have wide application prospects in deriving WQC and use in assessment of risks to ecosystems.

Movement of different strains in Drosophila melanogaster was continuously observed by using computer interfacing techniques and was analyzed by permutation entropy (PE) after exposure to toxic chemicals, toluene (0.1 mg/m3) and formaldehyde (0.01 mg/m3). The PE values based on one-dimensional time series position (vertical) data were variable according to internal constraint (i.e. strains) and accordingly increased in response to external constraint (i.e. chemicals) by reflecting diversity in movement patterns from both normal and intoxicated states. Cross-correlation function revealed temporal associations between the PE values and between the component movement patterns in different chemicals and strains through the period of intoxication. The entropy based on the order of position data could be a useful means for complexity measure in behavioral changes and for monitoring the impact of stressors in environment.

Video tracking based biological early warning system achieved a great progress with advanced computer vision and machine learning methods. Ability of video tracking of multiple biological organisms has been largely improved in recent years. Video based behavioral monitoring has become a common tool for acquiring quantified behavioral data for aquatic risk assessment. Investigation of behavioral responses under chemical and environmental stress has been boosted by rapidly developed machine learning and artificial intelligence. In this paper, we introduce the fundamental of video tracking and present the pioneer works in precise tracking of a group of individuals in 2D and 3D space. Technical and practical issues suffered in video tracking are explained. Subsequently, the toxic analysis based on fish behavioral data is summarized. Frequently used computational methods and machine learning are explained with their applications in aquatic toxicity detection and abnormal pattern analysis. Finally, advantages of recent developed deep learning approach in toxic prediction are presented.