SADR: Self-Supervised Graph Learning With Adaptive Denoising for Drug Repositioning.

Traditional drug development is often high-risk and time-consuming. A promising alternative is to reuse or relocate approved drugs. Recently, some methods based on graph representation learning have started to be used for drug repositioning. These models learn the low dimensional embeddings of drug and disease nodes from the drug-disease interaction network to predict the potential association between drugs and diseases. However, these methods have strict requirements for the dataset, and if the dataset is sparse, the performance of these methods will be severely affected. At the same time, these methods have poor robustness to noise in the dataset. In response to the above challenges, we propose a drug repositioning model based on self-supervised graph learning with adptive denoising, called SADR. SADR uses data augmentation and contrastive learning strategies to learn feature representations of nodes, which can effectively solve the problems caused by sparse datasets. SADR includes an adaptive denoising training (ADT) component that can effectively identify noisy data during the training process and remove the impact of noise on the model. We have conducted comprehensive experiments on three datasets and have achieved better prediction accuracy compared to multiple baseline models. At the same time, we propose the top 10 new predictive approved drugs for treating two diseases. This demonstrates the ability of our model to identify potential drug candidates for disease indications.

Tacrolimus and paclitaxel co-loaded O/O ointment without surfactant: Synergistic combinations for the treatment of psoriasis.

Psoriasis is an autoimmune disorder disease with abnormally activated T lymphocytes and thickening of the epidermis. The mechanism of the action of tacrolimus and paclitaxel are matched with the two only known pathogenesis of psoriasis. However, there has been no report on tacrolimus combined with paclitaxel in the treatment of psoriasis until now. The O/O ointment was prepared for the topical application to overcome poor solubility, poor skin penetration, and erratic absorption of the two drugs. A high-speed shearing method was adopted to prepare the ointment, in which propylene carbonate was used to solve tacrolimus and paclitaxel completely. The ointment showed excellent stability, slow release of the drugs, better retention in psoriatic skin, and good skin tolerance. The therapeutic efficacy of ointment was evaluated with imiquimod induced psoriatic model, and the level of expression of psoriatic biochemical markers was evaluated using the PASI score and immunohistochemistry. The cumulative PASI score was 10.8 for the imiquimod induced group, 7.8 for the tacrolimus ointment group, 8.3 for the paclitaxel ointment and 5.3 for the tacrolimus-paclitaxel (1:1) ointment group, respectively. Ointment group with tacrolimus and paclitaxel indicated a significant improvement in the phenotypic features of the psoriatic skin treated. Compared with the imiquimod group, tacrolimus-paclitaxel (1:1) ointment group was significantly reduced the level of IL-17. The results confirm that tacrolimus and paclitaxel co-loaded ointment can be an effective strategy for the treatment of psoriasis.

Generation of sub-100 fs electron pulses for time-resolved electron diffraction using a direct synchronization method.

To investigate photoinduced phenomena in various materials and molecules, ultrashort pulsed x-ray and electron sources with high brightness and high repetition rates are required. The x-ray and electron's typical and de Broglie wavelengths are shorter than lattice constants of materials and molecules. Therefore, photoinduced structural dynamics on the femtosecond to picosecond timescales can be directly observed in a diffraction manner by using these pulses. This research created a tabletop ultrashort pulsed electron diffraction setup that used a femtosecond laser and electron pulse compression cavity that was directly synchronized to the microwave master oscillator (∼3 GHz). A compressed electron pulse with a 1 kHz repetition rate contained 228 000 electrons. The electron pulse duration was estimated to be less than 100 fs at the sample position by using photoinduced immediate lattice changes in an ultrathin silicon film (50 nm). The newly developed time-resolved electron diffraction setup has a pulse duration that is comparable to femtosecond laser pulse widths (35-100 fs). The pulse duration, in particular, fits within the timescale of photoinduced phenomena in quantum materials. Our developed ultrafast time-resolved electron diffraction setup with a sub-100 fs temporal resolution would be a powerful tool in material science with a combination of optical pump-probe, time-resolved photoemission spectroscopic, and pulsed x-ray measurements.

Modulation of terahertz radiation from graphene surface plasmon polaritons via surface acoustic wave.

We present a theoretical study of terahertz (THz) radiation induced by surface plasmon polaritons (SPPs) on a graphene layer under modulation by a surface acoustic wave (SAW). In our gedanken experiment, SPPs are excited by an electron beam moving on a graphene layer situated on a piezoelectric MoS2 flake. Under modulation by the SAW field, charge carriers are periodically distributed over the MoS2 flake, and this causes periodically distributed permittivity. The periodic permittivity structure of the MoS2 flake folds the SPP dispersion curve back into the center of the first Brillouin zone, in a manner analogous to a crystal, leading to THz radiation emission with conservation of the wavevectors between the SPPs and the electromagnetic waves. Both the frequency and the intensity of the THz radiation are tuned by adjusting the chemical potential of the graphene layer, the MoS2 flake doping density, and the wavelength and period of the external SAW field. A maximum energy conversion efficiency as high as ninety percent was obtained from our model calculations. These results indicate an opportunity to develop highly tunable and integratable THz sources based on graphene devices.

Fertilization and male fertility in the rotifer Brachionus calyciflorus in the presence of three environmental endocrines.

Many studies investigated the effects of environmental endocrine disruptors with the rotifer Brachionus calyciflorus. However, they focused on the reproductive behavior of rotifers, especially male-female fertilization, as a parameter in ecotoxicological and endocrine studies. In the present study, we used two environmental hormones (progesterone and testosterone) and one nonsteroidal antiandrogen (flutamide) at five different concentrations (0.5, 1, 2, 4, and 6 mg/L) to study the reproductive behavioral parameters of male rotifers. The average swimming speed of male rotifers in the blank group was 1.14 ±â€¯0.43 mm/s. After exposure for 1 h, testosterone improved the swimming speed of males, with the greatest effect at a concentration of 2-4 mg/L, whereas flutamide and progesterone inhibited the swimming speed. Copulatory behavior experiments showed that, compared with the control group, the recognition ability of males was improved by testosterone at 1, 2, and 3 h (P < 0.05). After 4, 5, and 6 h, progesterone substantially suppressed the mating recognition ability of males, where the density of each group was extremely low at 6 h. Flutamide had a similar effect on the mating recognition ability of male rotifers as that of progesterone. The male fertilization rate in B. calyciflorus increased significantly under testosterone exposure at different concentrations (P < 0.05), with the highest level at 2 mg/L (male fertility rate = 48.61 ±â€¯3.18%). The fertilization rate of male rotifers was suppressed by both progesterone and flutamide (P < 0.05), and higher drug concentrations had stronger suppressive effects.

Combined effects of microcystin and nitrite on the growth, lipid peroxidation, and antioxidant responses of the freshwater rotifer Brachionus calyciflorus.

Toxicants released during the degradation of cyanobacterial blooms, such as microcystin-LR (MC-LR) and nitrite (NO2-N), affect the growth of aquatic organisms. The freshwater rotifer Brachionus calyciflorus was exposed to solutions with different combined concentrations of MC-LR (0, 10, 50, 100, and 200µgL-1) and NO2-N (0, 2, 4, 6, and 8mgL-1) to assess the combined effects of MC-LR and NO2-N on life cycle parameters and oxidative stress. Single solutions of MC-LR 200µgL-1 and NO2-N 8mgL-1 were toxic to rotifers. MC-LR combined with NO2-N decreased population growth rate (r), survival, and reproduction, but increased reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) contents (p<0.01). Superoxide dismutase (SOD) and catalase (CAT) activities and mRNA expression levels of MnSOD, CuZnSOD, and CAT significantly decreased under high concentrations of MC-LR or NO2-N (p<0.05). ROS levels had negative correlations with antioxidant enzyme activities and expression levels of antioxidant genes (p<0.01). MC-LR and NO2-N had interactive effects on r, reproduction, ROS levels, MDA content, SOD activity, and expression levels of MnSOD and CAT (p<0.05). By contrast, these effects were antagonistic on survival, CAT activity, GSH content, and expression level of CuZnSOD (p>0.05). Results showed that cyanobacterial metabolites act synergistically and antagonistically to cause toxicity to B. calyciflorus. ROS-mediated toxicity was considered the mechanism by which MC-LR and NO2-N induce damage.

Effects of testosterone and flutamide on reproduction in Brachionus calyciflorus.

The effects of testosterone and flutamide on reproduction in Brachionus calyciflorus were studied. Asexual reproduction in B. calyciflorus was not affected by testosterone at different concentrations of flutamide. Flutamide in combination with 0, 25, 50, or 75 µg L-1 testosterone had a significant effect on mixis rate. The combination of 5 µg L-1 flutamide with 25 µg L-1 or 50 µg L-1 testosterone resulted in a mixis rate that was 2.2× lower than that with flutamide alone. Fertilization rate was significantly decreased by 7.5 µg L-1 flutamide in combination with 25, 50, or 75 µg L-1 testosterone. The number of resting eggs produced per mictic female was significantly lower at all concentrations of testosterone. A low concentration of flutamide in combination with testosterone resulted in antagonism, increasing the number of resting eggs produced. However, when testosterone was combined with a higher concentration of flutamide, resting egg production declined. Therefore, long-term exposure to either testosterone, flutamide, or a combination of these two compounds may significantly reduce resting egg production in rotifers. This implies that resting egg production is affected differently by hormone pathways.