Objectives
Coronavirus disease 2019 (COVID‐19) is rapidly spreading worldwide. Lianhua Qingwen capsule (LQC) has shown therapeutic effects in patients with COVID‐19. This study is aimed to discover ...its molecular mechanism and provide potential drug targets.
Materials and Methods
An LQC target and COVID‐19–related gene set was established using the Traditional Chinese Medicine Systems Pharmacology database and seven disease‐gene databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein‐protein interaction (PPI) network were performed to discover the potential mechanism. Molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein.
Results
A gene set of 65 genes was generated. We then constructed a compound‐target network that contained 234 nodes of active compounds and 916 edges of compound‐target pairs. The GO and KEGG indicated that LQC can act by regulating immune response, apoptosis and virus infection. PPI network and subnetworks identified nine hub genes. The molecular docking was conducted on the most significant gene Akt1, which is involved in lung injury, lung fibrogenesis and virus infection. Six active compounds of LQC can enter the active pocket of Akt1, namely beta‐carotene, kaempferol, luteolin, naringenin, quercetin and wogonin, thereby exerting potential therapeutic effects in COVID‐19.
Conclusions
The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of LQC. Akt1 is a promising drug target to reduce tissue damage and help eliminate virus infection.
A Lianhua Qingwen capsule (LQC) target and COVID‐19 related gene set is established to construct compound‐target pharmacology network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicate the regulating effect of LQC on apoptosis, antivirus, immune defense, and inflammatory response. Protein‐protein interaction network and critical subnetworks are constructed to identify hub gene target. The most significant gene, Akt 1, is selected to perform molecular docking with active compounds of LQC. Six compounds are finally recognized as potential anti‐COVID‐19 agents.
Peptide drug development has made great progress in the last decade thanks to new production, modification, and analytic technologies. Peptides have been produced and modified using both chemical and ...biological methods, together with novel design and delivery strategies, which have helped to overcome the inherent drawbacks of peptides and have allowed the continued advancement of this field. A wide variety of natural and modified peptides have been obtained and studied, covering multiple therapeutic areas. This review summarizes the efforts and achievements in peptide drug discovery, production, and modification, and their current applications. We also discuss the value and challenges associated with future developments in therapeutic peptides.
Abstract
While general relativity predicts only two tensor modes for gravitational-wave (GW) polarization, general metric theories of gravity allow for up to four additional modes, including two ...vector and two scalar modes. Observing the polarization modes of GWs could provide a direct test of the modified gravity. The stochastic GW background (SGWB), which can be detected by space-based laser-interferometric detectors at design sensitivity, will provide an opportunity to directly measure alternative polarization. In this paper, we investigate the performance of the LISA-TianQin network for detecting alternative polarizations of stochastic backgrounds, and propose a method to separate different polarization modes. First, we generalize the small antenna approximation to compute the overlap reduction functions for the SGWB with arbitrary polarization, which is suitable for any time-delay interferometry combination. Then we analyze the detection capability of LISA-TianQin for the SGWB with different polarizations. Based on the orbital characteristics of LISA-TianQin, we propose a method to distinguish different polarization modes from their mixed data. Finally, simulation tests are performed to verify the effectiveness of the method. The results of the simulations demonstrate that LISA-TianQin, when employing our proposed method, has the ability to differentiate between various polarization modes, with a specific emphasis on the ability to distinguish between the breathing and longitudinal modes.
Previous studies report that miR-1-3p, a member of the microRNA-1 family (miR-1), and functions as a tumor suppressor in several different cancers. However, little is known regarding the biological ...role and intrinsic regulatory mechanisms of miR-1-3p in prostate cancer (PCa).
In this study, the expression levels of miR-1-3p were first examined in PCa cell lines and tumor tissues by RT-qPCR and bioinformatics. The in vitro and in vivo functional effect of miR-1-3p was examined further. A luciferase reporter assay was conducted to confirm target associations.
We found that miR-1-3p was significantly downregulated in advanced PCa tissues and cell lines. Low miR-1-3p levels were strongly associated with aggressive clinicopathological features and poor prognosis in PCa patients. Ectopic expression of miR-1-3p in 22RV1 and LncaP cells was sufficient to prevent tumor cell growth and cell cycle progression in vitro and in vivo. Further mechanistic studies revealed that miR-1-3p could directly target the mRNA 3'- untranslated region (3'- UTR) of two central cell cycle genes, E2F5 and PFTK1, and could suppress their mRNA and protein expression. In addition, knockdown of E2F5 and PFTK1 mimicked the tumor-suppressive effects of miR-1-3p overexpression on PCa progression. Conversely, concomitant knockdown of miR-1-3p and E2F5 and PFTK1 substantially reversed the inhibitory effects of either E2F5 or PFTK1 silencing alone.
These data highlight an important role for miR-1-3p in the regulation of proliferation and cell cycle in the molecular etiology of PCa and indicate the potential for miR-1-3p in applications furthering PCa prognostics and therapeutics.
The configuration entropy was manipulated by introducing atoms with unique properties using the high throughput calculations, and five new disilicates with ideal properties which have lower thermal ...conductivity and controllable thermal expansion coefficient were obtained through composition design. From a microstructural perspective, the inclusion of atoms with larger ionic radius differences (reaching a 4.11 % contrast with Yb2Si2O7) can cause sever lattice shrinkage (9.49 % compared to single-component disilicates), which leads to lower thermal conductivity and a change in the thermal expansion coefficient. At 1200 °C, the thermal expansion coefficient of the five high-entropy disilicates ranged from 4.57 × 10-6 K−1 to 4.84 × 10-6 K−1, and the minimum thermal conductivity was only 1.14 W/m·K. Additionally, the local charge disorder facilitates the transfer of electrons around Si-O to Sc, which reduces the covalent bond strength of Si-O and regulates the thermal expansion coefficient. This phenomenon has been proved in the five non-equimolar high-entropy disilicates with different contents of Sc, effectively regulating the thermal expansion coefficient in 4.08 × 10-6 K−1 to 5.04 × 10-6 K−1. This study presents a novel method for controlling the thermal properties of disilicates and expands the possibilities for selecting thermal protective coating materials for ultra-high temperature SiC-based ceramic composites.
Collective motion of chiral particles in complex noise environments is investigated based on the Vicsek model. In the model, we added chirality, along with complex noise, affecting particles ...clustering motion. Particles can only avoid noise interference in a specific channel, and this consideration is more realistic due to the complexity of the environment. Via simulations, we find that the channel proportion,
p
, critically influences chiral particle synchronization. Specifically, we observe a disorder-order transition at critical
p
c
, only when
p
>
p
c
, the system can achieve global synchronization. Combined with our definition of spatial distribution parameter and observation of the model, the reason is that particles begin to escape from the noise region under the influence of complex noise. In addition, the value of
p
c
increases linearly with velocity, while it decreases monotonically with the increase in chirality and interaction radius. Interestingly, an appropriate noise amplitude minimizes
p
c
. Our findings may inspire novel strategies to manipulate self-propelled particles of distinct chirality to achieve desired spatial migration and global synchronization.
Graphical abstract
Objectives
Thyroid carcinoma (TC) represents a malignant neoplasm affecting the thyroid. Current treatment strategies include the removal of part of the thyroid; however, this approach is associated ...with a significant risk of developing hypothyroidism. In order to adequately understand the expression profiles of TNRC6C‐AS1 and STK4 and their potential functions in TC, an investigation into their involvement with Hippo signalling pathway and the mechanism by which they influence TC apoptosis and autophagy were conducted.
Methods
A microarray analysis was performed to screen differentially expressed lncRNAs associated with TC. TC cells were employed to evaluate the role of TNRC6C‐AS1 by over‐expression or silencing means. The interaction of TNRC6C‐AS1 with methylation of STK4 promoter was evaluated to elucidate its ability to elicit autophagy, proliferation and apoptosis.
Results
TNRC6C‐AS1 was up‐regulated while STK4 was down‐regulated, where methylation level was elevated. STK4 was verified as a target gene of TNRC6C‐AS1, which was enriched by methyltransferase. Methyltransferase’s binding to STK4 increased expression of its promoter. Over‐expressed TNRC6C‐AS1 inhibited STK4 by promoting STK4 methylation and reducing the total protein levels of MST1 and LATS1/2. The phosphorylation of YAP1 phosphorylation was decreased, which resulted in the promotion of SW579 cell proliferation and tumorigenicity.
Conclusion
Based on our observations, we subsequently confirmed the anti‐proliferative, pro‐apoptotic and pro‐autophagy capabilities of TNRC6C‐AS1 through STK4 methylation via the Hippo signalling pathway in TC.
Currently, it is still a significant challenge to simultaneously boost various reactions by one electrocatalyst with high activity, excellent durability, as well as low cost. Herein, hybrid ...trifunctional electrocatalysts are explored via a facile one‐pot strategy toward an efficient oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER). The catalysts are rationally designed to be composed by FeCo nanoparticles encapsuled in graphitic carbon films, Co2P nanoparticles, and N,P‐codoped carbon nanofiber networks. The FeCo nanoparticles and the synergistic effect from Co2P and FeCo nanoparticles make the dominant contributions to the ORR, OER, and HER activities, respectively. Their bifunctional activity parameter (∆E) for ORR and OER is low to 0.77 V, which is much smaller than those of most nonprecious metal catalysts ever reported, and comparable with state‐of‐the‐art Pt/C and RuO2 (0.78 V). Accordingly, the as‐assembled Zn–air battery exhibits a high power density of 154 mW cm−2 with a low charge–discharge voltage gap of 0.83 V (at 10 mA cm−2) and excellent stability. The as‐constructed overall water‐splitting cell achieves a current density of 10 mA cm−2 (at 1.68 V), which is comparable to the best reported trifunctional catalysts.
Trifunctional electrocatalysts based on FeCo/Co2P hybrid nanoparticles are reported, which have excellent activities and stabilities toward the oxygen reduction reaction, oxygen evolution reaction, and hydrogen evolution reaction. The as‐assembled Zn–air battery exhibits charge–discharge voltage gap of 0.83 V at 10 mA cm−2, and an as‐constructed overall water‐splitting cell achieves a current density of 10 mA cm−2 at 1.68 V.
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