Here, we report the hypoxia-responsive ionizable liposomes to deliver small interference RNA (siRNA) anticancer drugs, which can selectively enhance cellular uptake of the siRNA under hypoxic and low-pH conditions to cure glioma. For this purpose, malate dehydrogenase lipid molecules were synthesized, which contain nitroimidazole groups that impart hypoxia sensitivity and specificity as hydrophobic tails, and tertiary amines as hydrophilic head groups. These malate dehydrogenase molecules, together with DSPE-PEG2000 and cholesterol, were self-assembled into O′
1
,O
1
-(3-(dimethylamino)propane-1,2-diyl) 16-bis(2-(2-methyl-5-nitro-1
H
-imidazol-1-yl)ethyl) di(hexadecanedioate) liposomes (MLP) to encapsulate siRNA through electrostatic interaction. Our study showed that the MLP could deliver polo-like kinase 1 siRNA (siPLK1) into glioma cells and effectively enhance the cellular uptake of MLP/siPLK1 because of increased positive charges induced by hypoxia and low pH. Moreover, MLP/siPLK1 was shown to be very effective in inhibiting the growth of glioma cells both in vitro and in vivo. Therefore, the MLP is a promising siRNA delivery system for tumor therapy.
We present a novel multi-task convolutional neural network called Multi-task SonoEyeNet (M-SEN) that learns to generate clinically relevant visual attention maps using sonographer gaze tracking data on input ultrasound (US) video frames so as to assist standardized abdominal circumference (AC) plane detection. Our architecture consists of a generator and a discriminator, which are trained in an adversarial scheme. The generator learns sonographer attention on a given US video frame to predict the frame label (standardized AC plane / background). The discriminator further fine-tunes the predicted attention map by encouraging it to mimick the ground-truth sonographer attention map. The novel model expands the potential clinical usefulness of a previous model by eliminating the requirement of input gaze tracking data during inference without compromising its plane detection performance (Precision: 96.8, Recall: 96.2, F-1 score: 96.5).
Abiotic stresses such as water deficit, salt, and heat are major environmental factors that negatively affect plant growth, development, and productivity. Previous studies showed that overexpression of the Arabidopsis vacuolar H
+
-pyrophosphatase gene
AVP1
increases salt and water deficit stress tolerance and overexpression of the rice SUMO E3 ligase gene
OsSIZ1
improves heat and water deficit stress tolerance in transgenic plants. In this report, the effects of co-overexpression of
AVP1
and
OsSIZ1
in Arabidopsis on abiotic stress tolerance were studied. It was found that
AVP1/OsSIZ1
co-overexpressing plants performed significantly better than
AVP1
-overexpressing plants and
OsSIZ1
-overexpressing plants, and produced 100% more seed than wild-type plants under single stress or multiple stress conditions. The increased stress tolerance in
AVP1/OsSIZ1
co-overexpressing plants was substantially larger than the increased stress tolerance in
AVP1
-overexpressing plants and
OsSIZ1
-overexpressing plants under every abiotic stress condition tested. This research provides the proof-of-concept that crop yields might be substantially improved using this approach.
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