Biological solubility is one of the important basic parameters in the development process of poorly soluble drugs,but the current measurement methods are mainly based on a large number of experiments,which are time-consuming and cost-intensive.There is still a lack of effective theoretical models to accurately describe and predict the biological solubility of drugs to reduce costs.Therefore,in this study,osaprazole and irbesartan were selected as model drugs,and their solubility in solutions containing surfactants and biorelevant media was measured experimentally.By calculating the parameters of each component using the perturbed-chain statistical associating fluid theory(PC-SAFT)model,combined with pH-dependent and micellar solubilization models,the thermodynamic phase behavior of the two drugs was successfully modeled,and the predicted results were in good agreement with the experimental values.These results demonstrate that the model combination used provides important basic parameters and theoretical guidance for the development and screening of poorly soluble drugs and related formulations.
The kinetics of hydrogen oxidation reaction(HOR)declines with orders of magnitude when the electrolyte varies from acid to base.Therefore,unveiling the mechanism of pH-dependent HOR and narrowing the acid-base kinetic gap are indispensable and challenging.Here,the HOR behaviors of palladium phosphides and their counterpart(PdP_2/C,Pd_5P_2/C,Pd_3P/C,and Pd/C)in the whole pH region(from pH 1 to 13)are explored.Unexpectedly,there are non-monotonous relationships between their HOR kinetics and varied pHs,showing distinct inflection-point behaviors(inflection points and acid-base kinetic gaps).We find the inflection-point behaviors can be explained by the discrepant role of pH-dependent hydroxyl binding energy(OHBE)and hydrogen binding energy(HBE)induced HOR kinetics under the entire pH range.We further reveal that the strengthened OHBE is responsible for the earlier appearance of the inflection point and much narrower acid-base kinetic gap.These findings are conducive to understanding the mechanism of the pH-targeted HOR process,and provide a new strategy for rational designing advanced HOR electrocatalysts under alkaline electrolyte.
The normal operation of lysosome, mitochondria, Golgi apparatus and endoplasmic reticulum plays a significant role in maintaining cell homeostasis. Reflecting the state and function of lysosomes, viscosity is a pivotal parameter to assess the stability of microenvironment. Herein, based on TICT mechanism,a new NIR pH-dependent fluorescent probe DCIC with push-pull electronic moiety was synthesized to identify the lysosomes viscosity. In viscous media, DCIC was highly sensitive to viscosity, fluorescence intensity increased by 180 times as viscosity increased from 1.0 cp to 438.4 cp. In addition, DCIC have high localization ability for lysosome, mitochondria, Golgi apparatus, and endoplasmic reticulum and can monitor lysosomal viscosity fluctuations with laser confocal microscopy.
The initial pitting corrosion behavior triggered by inclusions in S420 low alloy steel in acidic artificial seawater(ASW)and weak-alkaline ASW was characterized.The geometric data of the corrosion pits formed in the ASW with different pH were calculated.The pH of the ASW has an obvious influence on the pit shape.The pits in acidic ASW exhibit a funnel shape,while those in weak-alkaline ASW present a cone shape with a larger pit volume.The reason for the difference in the morphology and size of the corrosion pits induced by inclusion is that it is easier to trigger micro-galvanic corrosion in different structures and different areas of the pits in the acidic environment.
Heng MaZhong-xue WangYue LiuYue-xiang WangTeng-fei WangQing-pu ZhangZhong-yu Cui
酞菁铁(FePc)是一种很有应用潜力的氧还原反应(ORR)非贵金属催化剂.FePc基催化材料的ORR活性通常在碱性条件下远远好于在酸性条件下的性能,但这种pH对其ORR活性影响的机理还不清楚.本文制备了全氟酞菁铁(FePcF_(16))与多壁碳纳米管(MWCNT)的复合材料FePcF_(16)/MWCNT,并在pH 1、4、7、10和13的电解液中评估了它的ORR活性.其中,在pH 13条件下,FePcF_(16)/MWCNT表现出优异的ORR性能,起始电位(E_(onset))和半波电位(E_(1/2))分别为1.011 V vs.RHE和0.875 V vs.RHE;随着pH的减小,ORR性能显著降低,pH 1时,E_(onset)和E_(1/2)分别降低为0.280 Vvs.RHE和0.185 V vs.RHE,表明FePcF_(16)/MWCNT的电化学活性在不同pH条件下具有显著差异.吸收光谱滴定实验和密度泛函理论计算证明FePcF_(16)在不同的pH条件下具有不同的电子结构,从而造成其ORR活性的pH依赖性.这项工作有利于提升对FePc基催化材料ORR电催化性能的认识,并为进一步设计相应的高性能催化材料提供了理论和实验基础.
Gamma-aminobutyric acid(GABA)is a natural non-protein functio nal amino acid,which has potential for fermentation industrial production by Lactobacillus brevis.This work investigated the batch fermentation process and developed a kinetic model based on substrate restrictive model established by experimental data from L25(5~6)orthogonal experiments.In this study,the OD600 value of fermentation broth was fixed to constant after reaching its maximum because the microorganism death showed no effect on the enzyme activity of glutamate decarboxylase(GAD).As pH is one of the key parameters in fermentation process,a pH-dependent kinetic model based on radial basis function was developed to enhance the practicality of the model.Furthermore,as to decrease the deviations between the simulated curves and the experimental data,the rolling correction strategy with OD600 values that was measured in real-time was introduced into this work to modify the model.Finally,the accu racy of the rolling corrected and pH-dependent model was validated by good fitness between the simulated curves and data of the initial batch fermentation(pH 5.2).As a result,this pH-dependent kinetic model revealed that the optimal pH for biomass growth is 5.6-5.7 and for GABA production is about 5,respectively.Therefore,the developed model is practical and convenient for the instruction of GABA fermentation production,and it has instructive significance for the industrial scale.
Min WuJuanjuan DingZhaofeng ZhangShengping YouWei QiRongxin SuZhimin He
mproving the eficacy of melanoma treatment remains an important global challenge.Here,we combined chemotherapy with protein tyrosine phosphatase nonreceptor type 2(Ptpn2)based immunotherapy in an effort to address this challenge.Shorthairpin RNA(shRNA)targeting Ptpn2 was coencapsulated with doxorubicin(DOX)in the cell membrane of MI macrophages(MIHD@RPR).The prepared nanoparticles(NPs)were effectively phagocytosed by B16F10 cells and MI macrophages,but not by MOmacrophages.Hence,NPevasion from the reticuloendothelial system(RES)was improved and NPenrichment in tumor sites increased.MIHD@RPR can directly kill tumor cells and stimulate immunogenic cell death(ICD)by DOX and downregulate Ptpn2.It can promote Ml macrophage polarization and dendritic cell maturation and increase the proportion of CD8+T cells.MIHD@RPR killed and inhibited the growth of primary melanoma and lung metastatic tumor celis without harming the surrounding tssue.These findings establish MIHD@RPR as a safe multifunctional nanoparticle capable of effectively combining chemotherapy and gene immunotherapies against melanoma.
