Targeting colorectal cancer with Herba Patriniae and Coix seed:Network pharmacology,molecular docking,and in vitro validation

BACKGROUND Herba Patriniae and Coix seed(HC)constitute a widely utilized drug combination in the clinical management of colorectal cancer(CRC)that is known for its diuretic,anti-inflammatory,and swelling-reducing properties.Although its efficacy has been demonstrated in a clinical setting,the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated.AIM To identify the active,CRC-targeting components of HC and to elucidate the mechanisms of action involved.METHODS Active HC components were identified and screened using databases.Targets for each component were predicted.CRC-related targets were obtained from human gene databases.Interaction targets between HC and CRC were identified.A“drug-ingredient-target”network was created to identify the core components and targets involved.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were conducted to elucidate the key pathways involved.Molecular docking between core targets and key components was executed.In vitro experiments validated core monomers.RESULTS Nineteen active components of HC were identified,with acacetin as the primary active compound.The predictive analysis identified 454 targets of the active compounds in HC.Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets,including 30 core targets.GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway.Molecular docking showed that acacetin exhibited an optimal interaction with AKT1,identifying PI3K,AKT,and P53 as key genes likely targeted by HC during CRC treatment.Acacetin inhibited HT-29 cell proliferation and migration,as well as promoted apoptosis,in vitro.Western blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-PI3K,p-Akt,and survivin,which likely contributed to CRC apoptosis.CONCLUSION Acacetin,the principal active compound in the HC pair,inhibited the proliferation and migration of HT-29 cells and promoted apoptosis through the PI3K/Akt/p53 signaling pathway.

A reinvestigation of low molecular weight components in SOA produced by cyclohexene ozonolysis

The ozonolysis of cyclohexene is an important model system for understanding the more complex reaction of O_3 with monoterpenes; however, many previous studies have come to qualitatively different conclusions about the composition of the secondary organic aerosol(SOA)formed in this system. In the present study, the composition of the SOA produced by cyclohexene ozonolysis in the absence of seed aerosols has been investigated online and off-line using synchrotron-based thermal desorption/tunable vacuum ultraviolet photoionization time-of-flight aerosol mass spectrometry(TD-VUV-TOF-PIAMS) in conjunction with a custom-built smog chamber. On the basis of the molecular ions observed by mass spectrometry at 11.5 e V, it was found that dicarboxylic acids, dialdehydes, and cyclic anhydrides are the predominant low molecular weight components in the particle phase. The results also indicated that TD-VUV-TOF-PIAMS coupled with filter sampling is a potentially useful tool for the investigation of SOA composition both in the field and in the laboratory.

Photoionization and Dissociation Study of 2-Methyl-2-propen-1-ol:Experimental and Theoretical Insights

The photoionization and dissociation of 2-methyl-2-propen-1-ol(MPO)have been investigated by using molecular beam experimental apparatus with tunable vacuum ultraviolet synchrotron radiation in the photon energy region of 8.0-15.5 eV.The photoionization efficiency(PIE)curves for molecule ion and fragment ions:C4H8O^+,C4H7O^+,C3H5O^+,C4H7^+,C4H6^+,C4H5^+,C2H4O^+,C2H3O+,C3H6^+,C3H5^+,C3H3^+,CH3O^+,CHO^+have been measured,and the ionization energy(IE)and the appearance energies(AEs)of the fragment ions have been obtained.The stable species and the first order saddle points have been calculated on the CCSD(T)/cc-pvTZ//B3LYP/6-31+G(d,p)level.With combination of theoretical and experimental results,the dissociative photoionization pathways of 2-methyl-2-propen-1-ol are proposed.Hydrogen migrations within the molecule are the dominant processes in most of the fragmentation pathways of MPO.

Experimental and Theoretical Study on Dissociative Photoionization of Cyclopentanone

The dissociative photoionization of cyclopentanone was investigated by means of a reflectron time-of-flight mass spectrometer(RTOF-MS)with tunable vacuum ultraviolet synchrotron radiation in the photon energy range of 9.0~15.5 eV.The photoionization efficiency(PIE)curves for molecular ion and fragment ions were measured.The ionization energy of cyclopentanone was determined to be 9.230.03 eV.Fragment ions from the dissociative photoionization of cyclopentanone were identified as C5H7O+,C4H5O+,C4H8+/C3H4O+,C3H3O+,C4H6+,C2H4O+,C3H6+,C3H5+,C3H4+,C3H3+,C2H5+and C2H4+.With the aid of the ab initio calculations at theωB97X-D/6-31+G(d,p)level of theory,the dissociative mechanisms of C5H8O+are proposed.Ring opening and hydrogen migrations are the predominant processes in most of the fragmentation pathways of cyclopentanone.

Correlation of c-fos and p16 expression in oral squamous cell carcinoma with cell cycle and cell invasion

Objective:To study the correlation of c-fos and p16 expression in oral squamous cell carcinoma with cell cycle and cell invasion.Methods: Patients with oral squamous cell carcinoma who underwent surgical resection in Zaozhuang Mining Group Central Hospital between June 2014 and March 2017 were selected as OSCC group of the research, and patients who received impacted tooth extraction and provided normal gingival mucosa tissue in the Zaozhuang Mining Group Central Hospital during the same period were selected as the control group. The lesion tissue and normal tissue were obtained from OSCC group and control group respectively to determine the expression of c-fos, p16, cell cycle molecules and cell invasion molecules.Results: c-fos mRNA expression in lesion tissue of OSCC group was significantly higher than that of control group, p16 mRNA expression was significantly lower than that of control group, and the c-fos mRNA expression was negatively correlated with p16 mRNA expression;Chk1 and Chk2 mRNA expression in lesion tissue of OSCC group were significantly lower than those of control group whereas NEK2, CyclinD1, MALAT1, Periostin,β-catenin and Vimentin mRNA expression were significantly higher than those of control group;Chk1 and Chk2 mRNA expression in OSCC lesion tissue with high c-fos expression were significantly lower than those in OSCC lesion tissue with low c-fos expression whereas NEK2, CyclinD1, MALAT1, Periostin,β-catenin and Vimentin mRNA expression were significantly higher than those in OSCC lesion tissue with low c-fos expression.Conclusion:The high expression of c-fos and the low expression of p16 in oral squamous cell carcinoma can accelerate cell cycle and promote cell invasion.

Inductively Coupled Plasma Mass Spectrometry as a Reference Method to Evaluate Serum Calcium Measurement Bias and the Commutability of Processed Materials during Routine Measurements

Background： Measuring total serum calcium is important for the diagnosis of diseases. Currently, results from commercial kits for calcium measurement are variable. Generally, the performance of serum calcium measurements is monitored by external quality assessment （EQA） or proficiency testing schemes. However, the commutability of the EQA samples and calibrators is often unknown, which limits the effectiveness of EQA schemes. The aim of this study was to evaluate the bias of serum calcium measurements and the commutability of processed materials. Methods： Inductively coupled plasma mass spectrometry was applied as a comparative method, and 14 routine methods were chosen as test methods. Forty-eight serum samples from individual patients and 25 processed materials were quantified. A scatter plot was generated from patient samples, and 95% prediction intervals were calculated to evaluate the commutability of the processed materials and measurement bias at three concentration levels was used to determine the accuracy of routine assays. Results： All assays showed high precision （total coefficient of variation [CV] 〈2.26%） and correlation coefficients （r 〉 0.99）. For all assays, the mean bias for the 48 patient samples ranged from 0.13 mmol/L to 0.00 mmol/L （-5.61 0.01%）, and the ranges for the three concentrations were 0.10-0.04 mmoUL （-5.71-2.35%）, -0.14-0.01 mmol/L （-5.80-0.30%）, and -0.19-0.04 mmol/L （-6.24-1.22%）. The EQA samples, calibrators, and animal sera exhibited matrix effects in some assays; human serum pools were commutable in all assays; certificate reference materials were commutable in most assays, and only GBW09152 exhibited a matrix effect in one assay： and aqueous reference materials exhibited matrix effects in most assays. Conclusions： Biases for most assays were within the acceptable range, although the accuracy of some assays needs improvement. Human serum pools prepared from patient samples were commutable, and the other tested materials exhibited a matrix effect.

基于涡量输运方程的离心泵空化涡动力学特性数值研究

空化是影响离心泵等水力机械安全运行的关键因素。为研究空化发生时离心泵内涡动力学特性,该文以一单级单吸离心泵为研究对象,基于修正的SST k-ω湍流模型结合Zwart空化模型进行空化流动数值模拟,并利用外特性试验结果验证了数值计算的准确性。结果表明:随着空化数的降低,泵内依次发生空化初生、轻度空化和不稳定空化;严重空化时,流道内空化尾部产生旋涡结构,涡动力学分析显示此处为高涡量区;不同方向上的涡拉伸项与涡扩张项对叶轮内涡量的生成起主要作用,斜压扭矩项在汽液交界面对涡量的生成具有重要贡献,科氏力项对涡量的影响最小。