护肝布祖热颗粒通过EGFR/Ras/PI3K/AKT信号通路改善免疫性肝损伤:一项网络药理学研究和实验验证

护肝布祖热颗粒是维吾尔族传统的护肝方。作者在先前的一项研究中通过调节免疫平衡和抑制IRF1/JNK信号诱导的细胞凋亡,探讨了HBG抗免疫性肝损伤(ILI)的机制。但不是所有的机制都得到了探讨。本研究通过体内实验及网络药理学进一步研究了HBG降低小鼠刀豆球蛋白A(ConA)诱导的ILI的机制。首先,TCMSP、PharmMapper和GeneCards数据库确定了HBG治疗ILI的活性化合物和关键靶点。通过网络药理学和分子对接对确定的关键靶点和相关信号通路进行筛选。ConA诱导的小鼠ILI模型探讨了HBG对抗ILI的疗效和机制;蛋白质印迹分析检测关键蛋白的表达水平;网络药理学鉴定了16个化合物和53个靶标。成分-靶向通路(C-T-P)网络和分子对接表明,EGFR、HRAS、AKT1和PIK3R1是HBG对抗ILI的关键靶点。此外,分子对接显示,前八种活性化合物的对接得分高于阈值。与ConA组相比,HBG显著上调p-EGFR、Ras、p-AKT、p-PI3K、p-BAD和Bcl-2的表达,并下调Bax、裂解caspase 9和3的蛋白水平。HBG通过EGFR/Ras/PI3K/AKT信号通路抑制细胞凋亡,从而减轻ILI。

Simultaneous removal of Pb and MTBE by mixed zeolites in fixed-bed column tests

The co-contamination of metals and organic pollutants,such as Pb and methyl tert-butyl ether(MTBE),in groundwater,has become a common and major phenomenon in many contaminated sites.This study evaluated the feasibility of their simultaneous removal with permeable reactive barrier(PRB)packed with mixed zeolites(clinoptilolite and ZSM-5)using fixed-bed column tests and breakthrough curve modeling.The effect of grain size on the permeability of PRB and removal efficacy was also assessed by granular and power clinoptilolite.The replacement of granular clinoptilolite by powder clinoptilolite largely reduced the breakthrough time but increased the saturation time nearly fourfold.The column adsorption capacity of clinoptilolite powders almost tripled that of clinoptilolite granules(130.6mg/g versus 45.3 mg/g)due to higher specific surface areas.The minimum thickness and corresponding longevity of PRB were calculated as 7.12 cm and 321.5 min when 5%of granular clinoptilolite was mixed with 5%ZSM-5 and 90%sand as mixed PRB reactive media compared with 10.86 cm and 1230.2 min for the application of powder clinoptilolite.This study is expected to provide theoretical support and guidance for the practical application of mixed adsorbents in PRBs.

Identification of pollution sources in rivers using a hydrodynamic diffusion wave model and improved Bayesian-Markov chain Monte Carlo algorithm

Water quality restoration in rivers requires identification of the locations and discharges of pollution sources,and a reliable mathematical model to accomplish this identification is essential.In this paper,an innovative framework is presented to inversely estimate pollution sources for both accident preparedness and normal management of the allowable pollutant discharge.The proposed model integrates the concepts of the hydrodynamic diffusion wave equation and an improved Bayesian-Markov chain Monte Carlo method(MCMC).The methodological framework is tested using a designed case of a sudden wastewater spill incident(i.e.,source location,flow rate,and starting and ending times of the discharge)and a real case of multiple sewage inputs into a river(i.e.,locations and daily flows of sewage sources).The proposed modeling based on the improved Bayesian-MCMC method can effectively solve high-dimensional search and optimization problems according to known river water levels at pre-set monitoring sites.It can adequately provide accurate source estimation parameters using only one simulation through exploration of the full parameter space.In comparison,the inverse models based on the popular random walk Metropolis(RWM)algorithm and microbial genetic algorithm(MGA)do not produce reliable estimates for the two scenarios even after multiple simulation runs,and they fall into locally optimal solutions.Since much more water level data are available than water quality data,the proposed approach also provides a cost-effective solution for identifying pollution sources in rivers with the support of high-frequency water level data,especially for rivers receiving significant sewage discharges.

Performance evaluation on the pollution control against wet weather overflow based on on-site coagulation/flocculation in terminal drainage pipes

The pollution caused by wet weather overflow in urban drainage systems is a main factor causing blackening an odorization of urban rivers.The conventional overflow treatment based on coagulation/flocculation in terminal drainage systems requires relatively large space and long retention time demand that makes it not applicable in crowded urban drainage systems or under heavy rains.On-site coagulation/flocculation in terminal drainage pipes was proposed in this study which was aimed to transfer the coagulation/flocculation process to the inside of pipes at the terminal drainage system to save space and reduce the retention time of the coagulation/flocculation process.The optimized dose of chemicals was studied first which was 80 mg/L of coagulant and 0.8 mg/L of flocculant.Settling for only 5 min can remove most of the pollutants at 406.5 m of transmission distance.In addition,the relation of wet weather overflow rate and concentration of pollution load on the on-site coagulation/flocculation process was investigated,which indicated that high removal of pollutant was gained at a large range of flow velocity and pollutant concentration.Finally,the study confirmed electric neutralization,bridging,and net capture as the major mechanisms in this process,and further optimization was proposed.The proposed process can reduce much turbidity,chemical oxygen demand,and total phosphorous,but hardly remove soluble ammonia and organics.This work provides scientific guidance to address wet weather overflow in terminal drainage pipes.