The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC-Q-TOF/MS

Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation

Reducing the gap between streaming and non-streaming Transducer-based ASR by adaptive two-stage knowledge distillation

Transducer is one of the mainstream frameworks for streaming speech recognition. There is a performance gap between the streaming and non-streaming transducer models due to limited context. To reduce this gap, an effective way is to ensure that their hidden and output distributions are consistent, which can be achieved by hierarchical knowledge distillation. However, it is difficult to ensure the distribution consistency simultaneously because the learning of the output distribution depends on the hidden one. In this paper, we propose an adaptive two-stage knowledge distillation method consisting of hidden layer learning and output layer learning. In the former stage, we learn hidden representation with full context by applying mean square error loss function. In the latter stage, we design a power transformation based adaptive smoothness method to learn stable output distribution. It achieved 19\% relative reduction in word error rate, and a faster response for the first token compared with the original streaming model in LibriSpeech corpus

N‑Linked Glycosylation Prevents Deamidation of Glycopeptide and Glycoprotein

Deamidation has been recognized as a common spontaneous pathway of protein degradation and a prevalent concern in the pharmaceutical industry; deamidation caused the reduction of protein/peptide drug efficacy and shelf life in several cases. More importantly, deamidation of physiological proteins is related to several human diseases and considered a timer for the diseases. N-linked glycosylation has a variety of significant biological functions, and it interestingly occurs right on the deamidation site-asparagine. It has been perceived that N-glycosylation could prevent deamidation, but experimental support is still lacking for clearly understanding the role of N-glycosylation on deamidation. Our results presented that deamidation is prevented by naturally occurring N-linked glycosylation. Glycopeptides and corresponding nonglycosylated peptides were used to compare their deamidation rates. All the nonglycosylated peptides have different half-lives ranging from one to 20 days, for the corresponding glycosylated peptides; all the results showed that the deamidation reaction was significantly reduced by the introduction of N-linked glycosylation. A glycoprotein, RNase B, also showed a significantly elongated deamidation half-life compared to nonglycosylated protein RNase A. At last, N-linked glycosylation on INGAP-P, a therapeutic peptide, increased the deamidation half-life of INGAP-P as well as its therapeutic potency

Beta

Our team designed this game based on the theme word Traffic. The main reason about this is that Traffic could be an easy theme to create game. It is a simple game, but we actually met lots of difficulties during the process. The final project actually has huge differences with what I thought. For example, at the beginning, to best express the theme word we chose, we decided to use elements like little cars and a highway to construct it. In our game, players just need to use arrow keys to control. In my mind, the motion of our little red car should be regular. There are 4 lanes in the highway. When player press left or right bottom, the red car should only move one lane and also the same distance. We tried to let it move like 50 on the X coordination, but it’s seems stupid when the car moves and has some conflict with other settings. Therefore, we finally changed to the way that move as much as players want. There are some other kind of vehicles like police cars and some other color ones as well, these are what players need to avoid in our game. We used to put them on arranged places on a long highway which used to provide extent playable time. The difficulty change will increase or decrease those arranged cars. However, I thought that’s boring if someone want to play it again, so we changed the background to a loop and randomly create vehicles on highway. Difficulties will increase with time goes on and reach a maximum. Also, we used to have an end point on the highway, we removed it when we decided to loop the background. Under this circumstance, there is no winning condition and no way to win this game. We just set a limit life and a score based on time. In other words, players need to do their best to survive on this highway. When we tested the game, I found our game is more playable then the initial goal. The red car used to be only allowed to drive on 4 lanes, but now I can control it avoid other vehicles with a very close distance. Also, sometimes it seems surrounded by other vehicles, but they will destroy themselves by collisions. These elements make our game more playable. Xuqi and Kaisen usually say our game looks like drive on highway 17, but I don’t agree with them. Highway 17 is dangerous because of its winding topography, but in our game is dangerous because of those rude vehicles. We set those 3 different vehicles with three different speed. When two of them collide with each other, both will be destroyed and explosive. We hope people will know how dangerous it is when driving rude. We played lots of examples in construct 3 and see how it works to make our game better and innovative. The initial long highway is a typical example. We didn’t know how to make a highway at the beginning until we played the game Glokar. It uses several repeated backgrounds to make the playable time long enough. So we make our game just like it, but unfortunately we found this method is not suitable for our game. All of those games are awesome whatever on graph or entertainment. We try to learn how to make a game through their eventsheets, but some of them are too difficult to understand and some function are not free. In this case, we asked Tas and try to make our idea possible in our own way. For example, we want to make our car be unbeatable after one collision and flash. We made our car unable to touch and disappear a while and appear a while to create a flash scene. However, suddenly we found that there is a flash function, then we had to modify it. Finally, we successfully make a playable endless which brings more possibility to players. We overcome some difficulties and avoid some difficulties. We set random vehicles, which could give the game more possibilities like survive from besiege after enemies collide with others. We create a loop background to make the game have long enough play time. We give the red car a smooth control to give player chance to find gap to avoid their surround. I believe all of these elements could make our game innovative. Although there were so many problem and difficulties, we believe we did our best to create a good playable game.   Xuqi and I made lots of changes in our game on July 26, when Kaisen is on flight back to China, so there maybe some differences between his statement and our game

Beta

Our team designed this game based on the theme word Traffic. The main reason about this is that Traffic could be an easy theme to create game. It is a simple game, but we actually met lots of difficulties during the process. The final project actually has huge differences with what I thought. For example, at the beginning, to best express the theme word we chose, we decided to use elements like little cars and a highway to construct it. In our game, players just need to use arrow keys to control. In my mind, the motion of our little red car should be regular. There are 4 lanes in the highway. When player press left or right bottom, the red car should only move one lane and also the same distance. We tried to let it move like 50 on the X coordination, but it’s seems stupid when the car moves and has some conflict with other settings. Therefore, we finally changed to the way that move as much as players want. There are some other kind of vehicles like police cars and some other color ones as well, these are what players need to avoid in our game. We used to put them on arranged places on a long highway which used to provide extent playable time. The difficulty change will increase or decrease those arranged cars. However, I thought that’s boring if someone want to play it again, so we changed the background to a loop and randomly create vehicles on highway. Difficulties will increase with time goes on and reach a maximum. Also, we used to have an end point on the highway, we removed it when we decided to loop the background. Under this circumstance, there is no winning condition and no way to win this game. We just set a limit life and a score based on time. In other words, players need to do their best to survive on this highway. When we tested the game, I found our game is more playable then the initial goal. The red car used to be only allowed to drive on 4 lanes, but now I can control it avoid other vehicles with a very close distance. Also, sometimes it seems surrounded by other vehicles, but they will destroy themselves by collisions. These elements make our game more playable. Xuqi and Kaisen usually say our game looks like drive on highway 17, but I don’t agree with them. Highway 17 is dangerous because of its winding topography, but in our game is dangerous because of those rude vehicles. We set those 3 different vehicles with three different speed. When two of them collide with each other, both will be destroyed and explosive. We hope people will know how dangerous it is when driving rude. We played lots of examples in construct 3 and see how it works to make our game better and innovative. The initial long highway is a typical example. We didn’t know how to make a highway at the beginning until we played the game Glokar. It uses several repeated backgrounds to make the playable time long enough. So we make our game just like it, but unfortunately we found this method is not suitable for our game. All of those games are awesome whatever on graph or entertainment. We try to learn how to make a game through their eventsheets, but some of them are too difficult to understand and some function are not free. In this case, we asked Tas and try to make our idea possible in our own way. For example, we want to make our car be unbeatable after one collision and flash. We made our car unable to touch and disappear a while and appear a while to create a flash scene. However, suddenly we found that there is a flash function, then we had to modify it. Finally, we successfully make a playable endless which brings more possibility to players. We overcome some difficulties and avoid some difficulties. We set random vehicles, which could give the game more possibilities like survive from besiege after enemies collide with others. We create a loop background to make the game have long enough play time. We give the red car a smooth control to give player chance to find gap to avoid their surround. I believe all of these elements could make our game innovative. Although there were so many problem and difficulties, we believe we did our best to create a good playable game.   Xuqi and I made lots of changes in our game on July 26, when Kaisen is on flight back to China, so there maybe some differences between his statement and our game

Oxidation of Cefalexin by Permanganate: Reaction Kinetics, Mechanism, and Residual Antibacterial Activity

The oxidation of cefalexin (CFX), a commonly used cephalosporin antibiotic, was investigated by permanganate (PM) in water. Apparent second-order rate constant of the reaction between CFX and PM was determined to be 12.71 ± (1.62) M−1·s−1 at neutral pH. Lower pH was favorable for the oxidation of CFX by PM. The presence of Cl− and HCO3− could enhance PM-induced oxidation of CFX, whereas HA had negligible effect on CFX oxidation by PM. PM-induced oxidation of CFX was also significant in the real wastewater matrix. After addition of bisulfite (BS), PM-induced oxidation was significantly accelerated owing to the generation of Mn(III) reactive species. Product analysis indicated oxidation of CFX to three products, with two stereoisomeric sulfoxide products and one di-ketone product. The thioether sulfur and double bond on the six-membered ring were the reactive sites towards PM oxidation. Antibacterial activity assessment indicated that the activity of CFX solution was significantly reduced after PM oxidation

Cu-Mediated Sulfonyl Radical-Enabled 5-<i>exo-trig</i> Cyclization of Alkenyl Aldehydes: Access to Sulfonylmethyl 1<i>H</i>‑Indenes

An efficient method for the construction of sulfonylmethyl 1<i>H</i>-indenes via Cu­(I)-mediated sulfonyl radical-enabled 5-<i>exo-trig</i> cyclization of alkenyl aldehydes has been developed for the first time. Mechanistic studies indicated that a radical addition–cyclization–elimination (RACE) process might be involved. The reaction features a relatively broad substrate scope, good annulation efficiency, and varying functional group tolerance

Biocompatible Shape Memory Blend for Self-Expandable Stents with Potential Biomedical Applications

Biocompatible poly­(propylene carbonate) (PPC)/polycaprolactone (PCL) shape memory blends were fabricated using melt blending. The shape memory performance of these blends was found to depend remarkably on their components. On addition of 25 vol % PCL, one blend (PL-25) achieved an optimal shape-fixing ratio (<i>R</i>_f) and -recovery ratio (<i>R</i>_r). Specifically, its <i>R</i>_r considerably increased by 24.1 and 50.0% compared with those of pure PPC and PCL, respectively, because of the restricted irreversible deformation of the amorphous chains cross-linked by tiny crystals. After undergoing three thermomechanical cycles, <i>R</i>_f and <i>R</i>_r reached 97.0%. The PL-25 blend was further melt-processed into a stent, which showed a fast response and self-expansion at 37 °C. These results, along with those obtained from evaluating the material’s blood compatibility, in vitro degradation and drug release behavior, demonstrated the great potential of PL-25 for biomedical applications

Visible-Light-Promoted α‑C(sp³)–H Amination of Ethers with Azoles and Amides

A visible-light-induced highly efficient C(sp3)–H amination of ethers with amides and azoles has been presented under mild conditions via a nitrogen- and carbon-centered radical coupling process. This protocol successfully utilizes 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and tert-butyl nitrite (TBN) as cocatalysts to deliver the aminated products of ethers under aerobic conditions. Notably, the developed reaction features the corresponding products in good yields (up to 93%) with a wide substrate scope. The mechanistic study indicates that C–N bond formation proceeds via a direct radical cross-coupling process. Preliminary biological activity analysis indicates that the resulting products have good and selective inhibitory activity on osteosarcoma (OS) cell lines and are promising for use as hits for drug discovery