Responses of Karenia mikimotoi to allelochemical linoleic acid: Growth inhibition, photosynthetic damage, oxidative stress and cell apoptosis

Linoleic acid (LA), a potentially algae-inhibiting chemical released by macroalgae, has been shown to hinder the growth of numerous bloom-forming species. The allelopathic effects of LA (varying from 100 μg/L to 900 μg/L) on harmful microalgae K. mikimotoi were examined using population growth dynamics and physiological levels of K. mikimotoi. LA (>500 μg/L) strongly inhibited algal growth with most cells halted at the S and G2 phases and an evident drop in photosynthetic pigments (chlorophyll a (chl a), chlorophyll c (chl c) and carotenoids). Furthermore, chlorophyll fluorescence parameters such as Fv/Fm, PI, ETo/RC showed a declining trend whereas ABS/RC, DIo/RC, TRo/RC showed an increasing trend with increasing LA exposure concentrations. The level of intracellular reactive oxygen species (ROS) was considerably higher, indicating that LA promoted oxidative stress in K. mikimotoi. Excessive ROS promoted apoptosis in K. mikimotoi, which was noted by increased activity of caspase-3, caspase-9, and flow cytometry (FCM) data. Furthermore, N-acetylcysteine (NAC) and N-Acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO) lowered the apoptotic rates of the LA-treated algal cells, indicating that the aforementioned inhibitors delayed K. mikimotoi apoptosis under LA treatment. To summarize, cell cycle arrest of K. mikimotoi is less sensitive to ROS, but the overproduction of ROS generated by LA activated caspase-3 and caspase-9, which further promoted the apoptosis of K. mikimotoi. This research showed that LA might have great potential and application prospects in controlling the outbreak of harmful algae

Analysis of Leakage Current of HfO2/TaOx-Based 3-D Vertical Resistive Random Access Memory Array

Three-dimensional vertical resistive random access memory (VRRAM) is proposed as a promising candidate for increasing resistive memory storage density, but the performance evaluation mechanism of 3-D VRRAM arrays is still not mature enough. The previous approach to evaluating the performance of 3-D VRRAM was based on the write and read margin. However, the leakage current (LC) of the 3-D VRRAM array is a concern as well. Excess leakage currents not only reduce the read/write tolerance and liability of the memory cell but also increase the power consumption of the entire array. In this article, a 3-D circuit HSPICE simulation is used to analyze the impact of the array size and operation voltage on the leakage current in the 3-D VRRAM architecture. The simulation results show that rapidly increasing leakage currents significantly affect the size of 3-D layers. A high read voltage is profitable for enhancing the read margin. However, the leakage current also increases. Alleviating this conflict requires a trade-off when setting the input voltage. A method to improve the array read/write efficiency is proposed by analyzing the influence of the multi-bit operations on the overall leakage current. Finally, this paper explores different methods to reduce the leakage current in the 3-D VRRAM array. The leakage current model proposed in this paper provides an efficient performance prediction solution for the initial design of 3-D VRRAM arrays

Novel harmine derivatives as potent acetylcholinesterase and amyloid beta aggregation dual inhibitors for management of Alzheimer’s disease

AbstractIn this study, a series of potential ligands for the treatment of AD were synthesised and characterised as novel harmine derivatives modified at position 9 with benzyl piperazinyl. In vitro studies revealed that the majority of the derivatives exhibited moderate to potent inhibition against hAChE and Aβ1 − 42 aggregation. Notably, compounds 13 and 17d displayed potent drug − likeness and ADMET properties, demonstrating remarkable inhibitory activities towards AChE (IC50 = 58.76 nM and 89.38 nM, respectively) as well as Aβ aggregation (IC50 = 9.31 μM and 13.82 μM, respectively). More importantly, compounds 13 and 17d showed exceptional neuroprotective effects against Aβ1 − 42−induced SH − SY5Y damage, while maintaining low toxicity in SH − SY5Y cells. Further exploration of the mechanism through kinetic studies and molecular modelling confirmed that compound 13 could interact with both the CAS and the PAS of AChE. These findings suggested that harmine derivatives hold great potential as dual − targeted candidates for treating AD