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The requirement of improving efficiency and performance leads to the continuous development of furnaces and burners. For this purpose, it is necessary to establish a model suitable for industrial production and adjust it according to industrial demand. In this paper, a comprehensive numerical model is developed to characterize the combustion, heat transfer, and slab heating in an indirect reheating furnace with pulse combustion. To realize the pulse combustion process, a pulse control approach based on a user-defined function (UDF) was proposed to control the radiant tube burner state. Indirect heat transfer in the furnace was realized by coupling the radiant tubes and the furnace as a whole. In a simulation with the eddy dissipation concept (EDC) model, results from the four-step mechanism were in close accordance with those of the GRI 3.0 mechanism, and both mechanisms could describe the combustion process in detail. However, the calculation time of the EDC model with the four-step mechanism was reduced significantly. Thus, the EDC model with the four-step mechanism was selected as the ideal combustion model used for further simulation research. Through experimental validation, the simulation results of the developed model using the EDC model with the four-step mechanism showed a good agreement with the experimental results. Additionally, with this model, the effects of oxygen-enriched combustion with 74 vol % N2 and 26 vol % O2 in the oxidizer and inlet-change case with a fuel inlet and a primary air inlet on the performance of an indirect reheating furnace with pulse combustion were specially studied. The maximum flame temperature and the average temperature of the furnace atmosphere increased from 2046 to 2175 K and from 1241 to 1279 K for increased oxygen concentration, respectively. Compared with air-fuel combustion, the discharging slab temperature reached a growth of 2.9% in oxygen-enriched combustion. After changing the inlet boundary of the radiant tube burners, since the excessive combustion in the burner's combustion chamber was avoided and the full combustion of fuel in the radiant tubes was promoted, the flame intensity in the radiant tubes was enhanced and the maximum flame temperature reached 2196 K. At the same time, the mole fraction of CO at the outlet became smaller and the slab temperature in all zones of the furnace increased by more than 3.5%. This study showed that higher efficiency of an indirect reheating furnace with pulse combustion can be achieved by oxygen-enriched combustion and changing the inlet boundary of the burners.

Fermentation using Corynebacterium glutamicum is an important method for the industrial production of amino acids. However, conventional fermentation processes using C. glutamicum are susceptible to microbial contamination and therefore require equipment sterilization or antibiotic dosing. To establish a more robust fermentation process, l-lysine-producing C. glutamicum was engineered to efficiently utilize xenobiotic phosphite (Pt) by optimizing the expression of Pt dehydrogenase in the exeR genome locus. This ability provided C. glutamicum with a competitive advantage over common contaminating microbes when grown on media containing Pt as a phosphorus source instead of phosphate. As a result, the engineered strain could produce 41.00 g/L l-lysine under nonsterile conditions during batch fermentation for 60 h, whereas the original strain required 72 h to produce 40.78 g/L l-lysine under sterile conditions. Therefore, the recombinant strain can efficiently produce l-lysine under nonsterilized conditions with unaffected production efficiency. Although this anticontamination strategy has been previously reported for other species, this is the first time it has been demonstrated in C. glutamicum; these findings should aid in the further development of cost-efficient amino acid fermentation processes.

[Image: see text] Osteoarthritis (OA) treatment is a highly unmet medical need. Development of a disease-modifying OA drug (DMOAD) is challenging with no approved drugs on the market. Inhibition of ADATMS-4/5 is a promising OA therapeutics to target cartilage degradation and potentially can reduce joint pain and restore its normal function. Starting from the reported ADAMTS-5 inhibitor GLPG1972, we applied a scaffold hopping strategy to generate a novel isoindoline amide scaffold. Representative compound 18 showed high potency in ADATMS-4/5 inhibition, as well as good selectivity over a panel of other metalloproteases. In addition, compound 18 exhibited excellent druglike properties and showed better pharmacokinetic (PK) profiles than GLPG1972 cross-species. Compound 18 demonstrated dose-dependent efficacy in two in vivo rat osteoarthritis models.

The performance of a bismuth oxychloride (BiOCl)-based quartz crystal microbalance (QCM) humidity sensor was studied using an oscillating circuit method. The BiOCl powder was prepared by a hydrolysis method. Scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy were used to characterize the BiOCl sample. Its humidity-sensing property was analyzed by combining it with a QCM at room temperature (25 °C). Experimental results indicated that the BiOCl-based QCM sensor showed good humidity characteristics from 11.3 to 97.3%, such as good logarithmic frequency response to humidity levels (R2 = 0.994), fast response time (5.2 s)/recovery time (4.5 s), good reversibility, stability, repeatability, and low humidity hysteresis. In addition, the response to human nose breaths showed excellent practicability. Finally, the humidity sensing mechanism of the BiOCl-based QCM humidity sensor was discussed in detail. This work demonstrates that BiOCl is a promising candidate material for humidity detection.

In this research article, we reported a self-assembly approach to prepare a copper polyphosphate kinase 2 hybrid nanoflower and established a cofactor ADP regeneration system from AMP using the nanoflower. First, the structure of the hybrid nanoflower was confirmed by scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy, which indicated the successful loading of the enzyme in the hybrid nanoflower. Moreover, compared to the free enzyme, the hybrid nanoflower exhibited a better performance in ADP production and possessed wider catalytic pH and temperature ranges as well as improved storage stability. The hybrid nanoflower also exhibited well reusability, preserving 71.7% of initial activity after being used for ten cycles. In addition, the phosphorylation of glucose was conducted by utilizing ADP-dependent glucokinase coupled with the ADP regeneration system, in which the hybrid nanoflower was used for regenerating ADP from AMP. It was observed that the ADP regeneration system operated effectively at a very small amount of AMP. Thus, the hybrid nanoflower had great application potential in industrial catalytic processes that were coupled with ADP-dependent enzymes.

Human genetic evidence has identified the voltage-gated sodium channel Na

Chloramination of drinking waters has been associated with N-nitrosodimethylamine (NDMA) formation as a disinfection byproduct. NDMA is classified as a probable carcinogen and thus its formation during chloramination has recently become the focus of considerable research interest. In this study, the formation mechanisms of NDMA from ranitidine and trimethylamine (TMA), as models of tertiary amines, during chloramination were investigated by using density functional theory (DFT). A new four-step formation pathway of NDMA was proposed involving nucleophilic substitution by chloramine, oxidation, and dehydration followed by nitrosation. The results suggested that nitrosation reaction is the rate-limiting step and determines the NDMA yield for tertiary amines. When 45 other tertiary amines were examined, the proposed mechanism was found to be more applicable to aromatic tertiary amines, and there may be still some additional factors or pathways that need to be considered for aliphatic tertiary amines. The heterolytic ONN(Me)2-R(+) bond dissociation energy to release NDMA and carbocation R(+) was found to be a criterion for evaluating the reactivity of aromatic tertiary amines. A structure-activity study indicates that tertiary amines with benzyl, aromatic heterocyclic ring, and diene-substituted methenyl adjacent to the DMA moiety are potentially significant NDMA precursors. The findings of this study are helpful for understanding NDMA formation mechanism and predicting NDMA yield of a precursor.

Human genetic evidence has identified the voltage-gated sodium channel NaV1.7 as an attractive target for the treatment of pain. We initially identified naphthalene sulfonamide 3 as a potent and selective inhibitor of NaV1.7. Optimization to reduce biliary clearance by balancing hydrophilicity and hydrophobicity (Log D) while maintaining NaV1.7 potency led to the identification of quinazoline 16 (AM-2099). Compound 16 demonstrated a favorable pharmacokinetic profile in rat and dog and demonstrated dose-dependent reduction of histamine-induced scratching bouts in a mouse behavioral model following oral dosing.