Fuel Characteristics and Removal of AAEMs in Hydrochars Derived from Sewage Sludge and Corn Straw.

Co-hydrothermal carbonization (Co-HTC) of sewage sludge (SS) and corn straw (CS) for fuel preparation is a waste treatment method that reduces the pre-treatment cost of solid waste and biomass fuel. Based on the response surface methodology (RSM), a test was designed to prepare SS and CS hydrochars using a hydrothermal high-pressure reactor. The test examined the higher heating value (HHV) and the concentrations of alkali metals and alkaline earth metals (AAEMs) and Cl. The HHV of SS-hydrochar decreased with an increase in reaction temperature, but that of CS-hydrochar increased. The yield of CS-hydrochar was at 26.74−61.26%, substantially lower than that of SS-hydrochar. Co-hydrochar has the advantages of HHV and an acceptable yield. The HHV of co-hydrochar was 9215.51−12,083.2 kJ/kg, representing an increase of 12.6−47.6% over single component hydrochar, while the yield of co-hydrochar was 41.46−72.81%. In addition, the stabilities of AAEM and Cl in the co-hydrochar were Mg > Ca > K > Na > Cl. SS and CS had a synergistic effect on dechlorination efficiency (DE), which had a negative effect on the removal efficiency (RE) of Ca and Na. The optimal hydrocharization conditions were a temperature of approximately 246.14 °C, a residence time of approximately 90 min, and a mixing ratio of SS−CS of approximately 57.18%. The results offer a way to utilize SS and CS by Co-HTC and convert them into low-chlorine and low-alkali fuel, thus pushing the improvement of this promising waste-to-energy technology.

Reductive Activity and Mechanism of Hypoxia- Targeted AGT Inhibitors: An Experimental and Theoretical Investigation.

O6-alkylguanine-DNA alkyltransferase (AGT) is the main cause of tumor cell resistance to DNA-alkylating agents, so it is valuable to design tumor-targeted AGT inhibitors with hypoxia activation. Based on the existing benchmark inhibitor O6-benzylguanine (O6-BG), four derivatives with hypoxia-reduced potential and their corresponding reduction products were synthesized. A reductase system consisting of glucose/glucose oxidase, xanthine/xanthine oxidase, and catalase were constructed, and the reduction products of the hypoxia-activated prodrugs under normoxic and hypoxic conditions were determined by high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The results showed that the reduction products produced under hypoxic conditions were significantly higher than that under normoxic condition. The amount of the reduction product yielded from ANBP (2-nitro-6-(3-amino) benzyloxypurine) under hypoxic conditions was the highest, followed by AMNBP (2-nitro-6-(3-aminomethyl)benzyloxypurine), 2-NBP (2-nitro-6-benzyloxypurine), and 3-NBG (O6-(3-nitro)benzylguanine). It should be noted that although the levels of the reduction products of 2-NBP and 3-NBG were lower than those of ANBP and AMNBP, their maximal hypoxic/normoxic ratios were higher than those of the other two prodrugs. Meanwhile, we also investigated the single electron reduction mechanism of the hypoxia-activated prodrugs using density functional theory (DFT) calculations. As a result, the reduction of the nitro group to the nitroso was proven to be a rate-limiting step. Moreover, the 2-nitro group of purine ring was more ready to be reduced than the 3-nitro group of benzyl. The energy barriers of the rate-limiting steps were 34-37 kcal/mol. The interactions between these prodrugs and nitroreductase were explored via molecular docking study, and ANBP was observed to have the highest affinity to nitroreductase, followed by AMNBP, 2-NBP, and 3-NBG. Interestingly, the theoretical results were generally in a good agreement with the experimental results. Finally, molecular docking and molecular dynamics simulations were performed to predict the AGT-inhibitory activity of the four prodrugs and their reduction products. In summary, simultaneous consideration of reduction potential and hypoxic selectivity is necessary to ensure that such prodrugs have good hypoxic tumor targeting. This study provides insights into the hypoxia-activated mechanism of nitro-substituted prodrugs as AGT inhibitors, which may contribute to reasonable design and development of novel tumor-targeted AGT inhibitors.

A Generic Sure Independence Screening Procedure.

Extracting important features from ultra-high dimensional data is one of the primary tasks in statistical learning, information theory, precision medicine and biological discovery. Many of the sure independent screening methods developed to meet these needs are suitable for special models under some assumptions. With the availability of more data types and possible models, a model-free generic screening procedure with fewer and less restrictive assumptions is desirable. In this paper, we propose a generic nonparametric sure independence screening procedure, called BCor-SIS, on the basis of a recently developed universal dependence measure: Ball correlation. We show that the proposed procedure has strong screening consistency even when the dimensionality is an exponential order of the sample size without imposing sub-exponential moment assumptions on the data. We investigate the flexibility of this procedure by considering three commonly encountered challenging settings in biological discovery or precision medicine: iterative BCor-SIS, interaction pursuit, and survival outcomes. We use simulation studies and real data analyses to illustrate the versatility and practicability of our BCor-SIS method.