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Necroptosis is a form of regulated cell death that has been implicated in multiple diseases. TNF-induced necroptosis is regulated by necrosomes, complexes consisting of RIPK1, RIPK3 and MLKL. In this study, by screening of a small-compound library, we identified dozens of compounds that inhibited TNF-induced necroptosis. According to the mechanisms by which they inhibited necroptosis, these compounds were classified into different groups. We then identified Ibrutinib as an inhibitor of RIPK3 and found that Quizartinib protected against the TNF-induced systemic inflammatory response syndrome in mice by inhibiting the activation of RIPK1. Altogether, our work revealed dozens of necroptosis inhibitors, suggesting new potential approaches for treating necroptosis-related diseases. Screening a library of compounds identifies several inhibitors of TNF-induced necroptosis, including Ibrutinib as an inhibitor of RIPK3 and Quizartinib as an indirect RIPK1 kinase activity inhibitor. [ABSTRACT FROM AUTHOR]

The crosslinking mechanism of glyoxal and asparagine was analyzed, and the relationship between the mechanism and practical performances of soy protein-based adhesives was also discussed. It is shown that when pH=1 and 3, glyoxal reacted with asparagine in the form of major cyclic ether compounds. When pH =5, glyoxal reacted with asparagine in two structural forms of sodium glycollate and cyclic ether compounds. However, amidogens of asparagine were easy to develop protonation under acid conditions. Supplemented by the instability of cyclic ether compounds, the reaction activity and reaction degree between glyoxal and asparagine were relatively small. Under alkaline conditions, glyoxal mainly reacted with asparagine in the form of sodium glycollate. With the increase of pH, the polycondensation was more sufficient and the produced polycondensation products were more stable. The reaction mechanism between glyoxal and asparagine had strong correspondence to the practical performances of the adhesives. Glyoxal solution could develop crosslinking reactions with soy protein under both acid and alkaline conditions. Bonding strength and water resistance of the prepared soy protein-based adhesives were increased significantly. When pH>7, glyoxal had relatively high reaction activity and reaction intensity with soy protein, and the prepared adhesives had high crosslinking density and cohesion strength, showing relatively high bonding strength, water resistance and thermal stability. [ABSTRACT FROM AUTHOR]

A new protein wood adhesive was studied with Camellia oleifera protein. Formaldehyde and N-(2)-L-Ala-L-Gln (LAG) were used as the model compounds of amino resins and Camellia oleifera protein, aiming to provide scientific foundations for the improvement and applications of Camellia oleifera protein adhesive by the reaction of model compounds. The experimental results demonstrate that, under alkaline conditions, formaldehyde is easier to react with Camellia oleifera protein by quicker reaction and lower curing temperature. Under acid conditions, amino hydroxymethylated structure of aliphatic series from LAG is difficult to form stable reactive intermediates and further polycondensation. Hydroxymethylation of end acylamino and peptide bond amino from LAG is relatively weak. Under alkaline conditions, the free aliphatic amino and acylamino of LAG both can make hydroxymethylation reaction with formaldehyde. In the polycondensation, hydroxymethyl amide is the initial structure and the reactive intermediate is produced by E1cb reaction of hydroxymethyl amide. Methylene bridge bonds and methylene ether bonds are structures of the polycondensation products, which are competing reactions. The former is mainly formed by the reaction between alkaline reactive intermediate and amino of aliphatic series, and the latter is produced by the reaction of reactive intermediate and amino of hydroxymethyl aliphatic series with hydroxymethyl amide. [ABSTRACT FROM AUTHOR]

Polyethylene glycol (PEG) was used as the modifying agent of cold-setting melamine–urea–formaldehyde (MUF) resin adhesive in this work. Effects of the amount of PEG on the flexibility of MUF resin, and its bonding properties, as well as water resistance were studied. Then, the flexibility improvement mechanism was also discussed in this paper. Results showed that: (1) the strength and flexibility of MUF resin were greatly improved by PEG. With a PEG addition lower than 0.72% on the total amount of MUF resin, PEG exerted simultaneous reinforcing and flexibility improvement on MUF resin. (2) Both dry and wet shear strength of MUF resin increased with the addition of PEG, reaching the maximum values with 1.80% PEG on the total amount of MUF. (3) The DSC and TG results showed that thermal stability of MUF is degraded with the addition of PEG. (4) SEM results indicated that the addition of PEG was beneficial to the flexibility of MUF resin. The larger the addition amount of PEG, the better the flexibility improvement. [ABSTRACT FROM AUTHOR]

Two types of urea–formaldehyde (UF) resin adhesives were synthesized with standard formaldehyde solution with 37% concentration and concentrated formaldehyde solution with 45% concentration. For 37% formaldehyde, 10% methanol was used as an inhibitor. For 45% formaldehyde, no more methanol was added. The chemical structure and changes during the resin preparation were analyzed. The performance of particleboards prepared with these resins was evaluated. The results indicated that the main difference between the concentrated formaldehyde and the standard formaldehyde was the higher content of methanol in the latter. Methanol affected the reaction during the preparation of UF resins and the final performance of the resins. Samples of the UF resin with standard formaldehyde taken at different stages during its preparation showed different contents of methylol groups, methylene ether bonds, uron structure, methylene bonds, and other groups compared to the resin prepared from concentrated formaldehyde. The performance concerning water resistance, mechanical performance, and formaldehyde emission of the particleboards prepared with the UF resin with concentrated formaldehyde was better than that with the resin with standard formaldehyde. [ABSTRACT FROM AUTHOR]

Epoxy resin (EPR) was used to crosslink with Camellia oleifera Abel. protein to prepare wood adhesive, and the bonding performance and curing characteristics of which were mainly investigated, and the synthesis mechanism was also discussed by using model compounds. The experimental results show that EPR can significantly improve the bonding performance of Camellia oleifera Abel. protein-based adhesive, and the maximum of which reaches 0.72 MPa satisfies the strength requirement of Type II plywood in GB/T 17657-2013. After alkali treatment, the protein can more easily crosslink with EPR at low curing temperature, and the adhesive has high degree of crystallinity of curing products, high degree of crosslinking reaction, and high bonding strength. The reaction mechanism of EPR-modified Camellia oleifera Abel. protein adhesive can be divided into resinification phase and curing phase. [ABSTRACT FROM AUTHOR]

Broussonetiapapyrifera leaf protein was used as a biomass feedstock to prepare wood adhesives, and the influence of cutting modes (cutting frequencies and cutting heights) on leaf protein content and reactivity was studied in this paper. Bonding performance of Broussonetiapapyrifera leaf protein-based adhesives were evaluated by shear strength of plywood. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetry (TG), and scanning electron microscope (SEM) were used to analyze them. The results indicated that: (1) the leaf protein content gradually increased as the cutting height increased, but it presented a decreasing trend as the cutting frequency increased. When the cutting frequency is two times per year and the cutting height is 30 cm, this leaf protein-based adhesive exhibited the best bonding strength with 0.75 MPa. (2) Cutting frequency and cutting height have no significant correlations to the reactivity of leaf protein with the crosslinker. (3) DSC and FTIR indicated that both leaf protein content and reactivity appeared to exert an influence on the bonding properties of the protein adhesives, and the latter is more pronounced. (4) TG and SEM analyses indicated that under different cutting modes, leaf protein content, especially protein reactivity, had a great effect on the thermal properties of the adhesives. (5) Contact angle analysis showed that Broussonetiapapyrifera leaf protein-based adhesives had good wettability on wood surfaces. Under different cutting modes with the difference of leaf protein content and reactivity, the crosslinking degree of the adhesives with crosslinker and compactness of the cured adhesives were different and thus affect their bonding strength and water resistance. [ABSTRACT FROM AUTHOR]

To guide the preparation of soy protein-based adhesives, the reaction between protein and formaldehyde as a possible cross-linker was studied in this paper under different pHs. To simplify the investigations, dipeptide N-(2)-l-alanyl-l-glutamine (AG) was used as a model compound for protein. Based on the analysis of the results of ESI-MS and 13C-NMR of the reaction products between AG and formaldehyde prepared under different pHs, it was found that the pH has strong effects on these reactions. Under strong acid conditions, such as pH 1–3, the methylolation reaction mainly occurred at the aliphatic amino groups of AG. However, it was very difficult for the resulted methylolated AG to be further condensed. Under weak acid conditions, such as pH 5, both the methylolation reaction between amido groups and formaldehyde and the further condensation reaction were possible. However, the condensation reaction was still rather weak under these conditions. At alkaline conditions, the methylolation reaction occurred between all of the three types of amino groups of AG and formaldehyde with both methylene bonds and methylene–ether bonds present in the system. Methylene bonds were mainly from the reaction between AG methylols and amido groups and aliphatic amino groups of AG. Ether bridges were formed between two methylolated AG mainly from amido groups. [ABSTRACT FROM AUTHOR]

Introduction: Laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy is gaining popularity as a treatment for choledochal cyst (CDC) in children. However, the learning curve for this challenging laparoscopic procedure has not been addressed. The aim of this study is to determine the characteristics of the learning curve of this procedure. This may guide the training in institutions currently not using this technique.Methods: A prospectively collected database comprising all medical records of the first 104 consecutive patients undergoing laparoscopic CDC excision and Roux-en-Y hepaticojejunostomy performed by one surgeon was studied. Multifactorial linear/logistic regression analysis was performed to identify patient-, surgeon-, and procedure-related factors associated with operating times, rates of adverse event, and length of postoperative stay.Results: Cumulative sum analysis demonstrated a learning curve for laparoscopic choledochal cyst excision of 37 cases. Comparing the early with the late experiences (37 vs. 67 cases), the surgeon-specific outcomes significantly improved in terms of operating times (352 vs. 240 min; P < 0.001), postoperative complication rate (13.5 vs. 1.5 %; P = 0.02), and the length of hospital stay (9.4 vs. 7.8 days; P = 0.01). After multivariate analyses, independent predictors of operating times included the completion of the learning curve (CLC) (OR 0.68, 95 % CI 0.63-0.73) and adhesion score (ORmiddle 1.25, 95 % CI 1.08-1.45; ORhigh 1.40, 95 % CI 1.20-1.62; compared with the low score); significant predictors of perioperative adverse outcomes were CLC (OR 0.07, 95 % CI 0.02-0.34) and comorbidities prior to the surgery (OR 30.65, 95 % CI 1.71-549.63). The independent predictors of length of postoperative stay included CLC, preoperative comorbidities, and perioperative adverse events.Conclusions: CLC for laparoscopic choledochal cyst excision is 37 cases. After CLC, not only the operative time is reduced, the complications, adverse results, and the length of hospital stay all decreased significantly. The learning curve can be used as the basis for performance guiding the training. [ABSTRACT FROM AUTHOR]

The competitive formation of the methylene and methylene ether bridges in the urea-formaldehyde reaction in alkaline solution was investigated by using C NMR and quantum chemistry calculations. Despite that the classical theory states that the condensations of methylolureas only form methylene ether bridges at alkaline pH, the competing formation of methylene bridges was observed in this study. The NMR spectra show that the methylene ether bridges are exclusively formed under conditions of 80 and 90 °C with F/U = 2/1. At 80 °C with F/U = 1/1, the linear methylene bridge (-NH-CH-NH-) began to compete with ether bridges, but it was minor. At 90 °C with F/U = 1/1, the methylene bridges were found to be much more competitive. The theoretically calculated energy barriers for the formation of different types of methylene ether bridges are lower than those for methylene bridges by 12-26 kJ/mol. The steric hindrance was proposed to be another important effect that suppresses the condensations between di- and tri-methylolureas to form the branched methylene bridges [-(HOCH)N-CH-NH- or -(HOCH)N-CH-N(CHOH)-]. However, the reaction between a free amino group -NH and a methylol group -CHOH was proposed to encounter no steric hindrance. Hence, once the higher temperature and lower F/U ratio were guaranteed, the competitive formation of linear methylene bridges was observed. [ABSTRACT FROM AUTHOR]