Relationship between the angiotensin Ⅱ type 2 receptor polymorphism and antihypertensive effect of valartan/Hydrochlorothiazide

目的 探讨原发性高血压患者α-内收蛋白基因单核苷酸多态性与原发性高血压及复方缬沙坦治疗疗效的关系.方法 应用直接测序方法对80例原发性高血压、80例肾性高血压及40例正常人群α-内收蛋白基因进行单核苷酸多态性分析.结果 α-内收蛋白G/T基因型及等位基因在3组中分布无显著差异(P＞0.05);复方缬沙坦对原发性高血压TT和GT基因型患者用药后血压的下降幅度比较差异有统计学意义(P＜0.05).结论 复方缬沙坦对原发性高血压患者的降压作用可能与a-内收蛋白基因多态性有关.     

Reverse shape selectivity of hexane isomer in ligand inserted MOF-74

Separation of linear, mono-branched, and di-branched isomers is critically important in the petrochemical industry. In this computational study, we demonstrate that the ligand inserted Mg-MOF-74 structure leads to a reverse selectivity effect (i.e. phenomenon that preferentially allows larger species molecules to permeate in a gas mixture) of hexane isomers in the resulting material. Molecular dynamics simulations suggest that strong confinement of the di-branched hydrocarbons in the small pores lead to reverse selectivity. Over a magnitude difference in diffusivity between linear alkanes and their di-branched isomers was observed, clearly showing the steric effects imposed by the pore structure.

The ligand inserted Mg-MOF-74 structure leads to a reverse selectivity effect (i.e. phenomenon that preferentially allows larger species molecules to permeate in a gas mixture) of hexane isomers in the resulting material.

In the petrochemical industry, separation of the hexane isomers is an important process that removes impurities for fuel purification and the isolation of mixtures for applied further reaction.^1,2 The sieving of n-hexane and its branched isomers is particularly interesting research because of the varying octane numbers in the isomers affecting the gasoline production,^3–5 and as such, it is imperative to facilitate separation of these isomers. Unfortunately, this separation is particularly challenging due to the similar polarizabilities and chemical inertness of the molecules, leading one to resort to highly energy expensive distillation processes.^1,6The presently used methods such as molecular sieving using zeolites and the conventional distillation processes still include mixtures of the isomers that lowers the overall octane number^7,8 compared to the pure di-branched molecule composition. To discover the adsorbent materials that can completely separate the isomers into their individual components, many researchers have investigated adsorbent materials with an appropriate pore size and shape.^9–12 Recently, metal–organic frameworks (MOFs) have attracted great deal of attention from the researchers due to their potential applications in gas separations,^13–20 CO₂ capture,^21,22 catalysis,^23–26 water harvesting^27–29 and several other applications.^30–32 MOFs are crystalline microporous materials composed of inorganic metal nodes and organic linkers^33–35 and via combining various metal clusters and organic linkers, MOFs can be tuned specifically to ideal shapes and pore chemical environment for targeted gas separations.^36–38 This tunability allows one to potentially design MOFs that are ideal for hexane isomers. Bárcia et al.³⁹ firstly used MOFs called Zn(BDC)(DABCO)_0.5 (MOF-1) to separate hexane isomers, although this MOF showed low adsorption capacities. Also, Herm et al.¹² synthesized a MOF named Fe₂(BDP)₃ (BDP²⁻ = 1,4-benzenedipyrazolate), which contain triangular pore channels that can discriminate hexane isomers better than the commercial standard. More recently, Lv et al.⁴⁰ demonstrated that [Fe₃(μ3-O)(COO)₆] and 2,2-bis(4-carboxyphenyl)-hexafluoropropane (6FDCA) have strong capability to separate n-hexane from its branched isomers on the basis of a kinetically controlled molecular sieve separation.Overall, conventional wisdom dictates that one would seek to design materials whose pore limiting diameter can separate the molecules of interest within the mixture. With that being said, there have been few observances where the ordering based on kinetic diameters is reversed (in what is called reverse selectivity).⁴¹ Previous study by Bárcia et al.⁴² used the concept of “length entropy” to describe the adsorption and separation behavior in UiO-66(Zr). They showed that UiO-66(Zr) preferentially adsorb branched alkanes over their linear isomer, in what they called “reverse selectivity”. Moreover, Pan et al.⁴³ described the unusual reverse selective separation of n-butane from normal hydrocarbons above C₄ in a fluorinated MOF with 1D channels. Additionally, reverse selectivity has also been mentioned in recent works with IRMOF-8 (ref. 44) and UiO-66@SiO₂ (ref. 45) with regards to linear and iso-alkane separation.In our previous computational work, we designed the ligand inserted MOF frameworks using the ligand insertion strategy. Using computational analysis, these structures showed increase in the working capacity of CO₂ under humid flue gas conditions,²² utility as a catalyst for enhanced ethane oxidation²⁵ and potential usage in water harvesting material.²⁹ In the current work, the dpt ligand inserted Mg-MOF-74 structures with 1-D channel was used to examine the reverse selectivity of hexane isomer and separation properties by considering mixtures of n-hexane and its branched isomers (2,2-dimethylbutane, 2,3-dimethylbutane, 2-methylpentane and 3-methylpentane). In the context of the hexane isomer separation, the inserted ligand finely tuned the shape and the size of the pores within the MOF such that branched isomer can reverse selectively pass through the MOF channel.Optimization of the MOFs and the hexane isomer binding energy calculations were conducted using the first-principles calculations through the density functional theory (DFT) as implemented by the plane-wave pseudopotential approach in Quantum Espresso.⁴⁶ The second version of a van der Waals dispersion-corrected density functional (vdW-DF2)⁴⁷ was used to describe the dispersion interactions. Ultrasoft pseudopotentials were used for GGA and vdW-DF2 calculations. A 2 × 2 × 2 k-point mesh was used for the Brillouin zone sampling in the reciprocal space. The kinetic energy and charge density planewave cutoff were set to 30 Ry and 240 Ry, respectively.All molecular dynamics simulations were carried out using the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) program.⁴⁸ In the simulations, the MOF structures are set to be fixed with the dpt ligand and the hexane isomers considered to be flexible, incorporating all intramolecular motions such as bond vibrations, bond angle bending, and torsional motions. All non-bonded interactions between the atoms were calculated using the Lennard-Jones (LJ) potential. Adsorbate–adsorbate and adsorbate–MOF interactions were truncated at 14 Å and at 12.8 Å with analytical tail-corrections applied for interactions beyond this cutoff distance, respectively. The LJ parameters for the atoms of the MOF were taken from the UFF⁴⁹ and The TraPPE force field were employed to model the inter- and intramolecular interactions of the hexane isomers as previous studies reported that these models accurately model the adsorption and diffusion properties of alkanes⁵⁰ and nHEX⁵¹ in the MOFs. Initially, all systems were equilibrated for 2 ns in an NVT ensemble, and afterwards, another 10 ns of simulation was performed in the NVT ensemble during which the equilibrated phase space trajectories were stored at every 10 ps. These trajectories were then used to analyze the diffusion behavior of the hexane isomers with the diffusion coefficients calculated from the mean square displacements (MSD) of the molecules using the Einstein''s relation.The ligand insertion strategy within the MOF-74 structure can be used to reconfigure the pore space to enhance the separation performance. To demonstrate this, a size-matching regulated ligand (2,4-di(4-pyridinyl)-1,3,5-triazine (dpt)) was inserted as shown in Fig. 1(a).Open in a separate windowFig. 1Illustration of pore space partitioned Mg-MOF-74 using ligands 2,4-di(4-pyridinyl)-1,3,5-triazine. (a) Viewed along z axis and (b) side view of the channels showing the cylindrical channel.The insertion of 2,4-di(4-pyridinyl)-1,3,5-triazine (dpt) ligands into the hexagonal channels of Mg-MOF-74 was demonstrated in our previous theoretical study on catalyst for ethane oxidation.²⁵ In the previous work, the computed DFT binding energy of the dpt ligand was −198.3 kJ mol⁻¹ in the Mg-MOF-74 structures, providing evidence that the ligands would stay intact and not wash away, post synthesis. The dpt ligands were inserted such that the distance between the two dpt ligands is 8.3 Å along the channel direction in the z-axis (Fig. 1(b)). In the alkane separations, configurational and length entropy effects may act in a completely different manner. These effects plays a bigger role for separating linear and branched alkanes in materials such as AFI⁵² and MOF-74 that have cylindrical channels. Hence, it is important to consider both the maximum diameter (i.e. molecular length)⁵³ of the molecules as well as kinetic diameter. As can be seen from 53,54

Hepatocarcinogenic potential of the glucocorticoid antagonist RU486 in B6C3F1 mice: effect on apoptosis,expression of oncogenes and the tumor suppressor gene <Emphasis Type="Italic">p</Emphasis> 53

Background

Glucocorticoids inhibit hepatocellular proliferation and modulate the expression of oncogenes and tumor suppressor genes via mechanisms involving the glucocorticoid receptor. Glucocorticoids also produce a receptor-mediated inhibitory effect on both basal and hormone-stimulated expression of a newly discovered family of molecules important for shutting off cytokine action. We therefore hypothesized that inhibiting glucocorticoid receptors may disturb hepatocellular growth and apoptosis. Consequently, we investigated the effect of RU486, a potent antagonist of the glucocorticoid receptor, on basal levels of hepatocellular proliferation and apoptosis in male B6C3F1 mice. Furthermore, we evaluated the effect of this compound on cellular genes involved in the regulation of these important processes.

Results

Data show that treatment of male B6F3C1 mice with RU486 (2 mg/kg/d, ip) for 7 days dramatically inhibited liver cell proliferation by about 45% and programmed hepatocellular death by approximately 66%. RU 486 also significantly increased hepatic expression of the oncogenes mdm2 and JunB, while reducing that of the tumor suppressor gene p53.

Conclusion

Exposure to RU486 may ultimately enhance the susceptibility of the liver to cancer risk by diminishing its ability to purge itself of pre-cancerous cells via apoptosis. This effect may be mediated through increases in the hepatic expression of the oncogene mdm2, coupled with decreases in that of the tumor suppressor gene p53. The decrease in hepatocellular proliferation caused by RU 486 may be related to effects other than its anti-glucocorticoid activity.

     

Massive lingual teratoma in a neonate

Teratoma of the tongue is a rare entity. We present a male newborn with massive lingual teratoma and cleft palate, which surprisingly did not cause immediate airway obstruction. This case illustrates a huge mass in the oral cavity, which was missed on antenatal ultrasonography because it did not present with polyhydramnios. The mass was excised under general anaesthesia. Histopathologically, it consisted of all three layers of embryonic elements with predominantly glial tissue. Postoperatively, the patient developed hypoglossal nerve palsy, and no recurrence was detected after four years.     

超声微泡介导野生型p53基因转染Y79细胞的实验研究

目的研究超声微泡介导wtp53（wild type p53）基因转染视网膜母细胞瘤（Y79）细胞的效率及作用效果。方法以一定能量的超声介导wtp53转染Y79细胞,分为（1）质粒＋微泡＋超声照射组;（2）质粒＋脂质体组;（3）质粒＋超声照射组;（4）空白对照组。RT-PCR检测wtp53mRNA,流式细胞仪检测细胞凋亡率。结果超声微泡介导的wtp53基因对Y79细胞的转染效率明显高于其他实验组,检测到的细胞凋亡率也明显高于其他组。结论超声微泡可达到高效的基因转染目的,wtp53对Y79细胞有明显抑制生长的作用。     

Detection of mesenteric ischemia by means of endoscopic visible light spectroscopy after luminal feeding

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64 Multidetector CT angiography in preoperative evaluation of hepatic artery

Purpose

To evaluate the role of 64 multidetector CT angiography in preoperative evaluation of hepatic artery in candidates who underwent hepatic resection.

Materials and methods

Sixty-seven patients underwent triphasic CT scan using 64 multidetector CT scanner. They were 33 with hepatocellular carcinoma, 21 with solitary metastases, seven potential donors for liver transplantation, five with gaint haemangiomas, and one with large primary Non-Hodgkin lymphoma. The images were analyzed for the depiction of hepatic artery. The frequencies of anatomical variants of the hepatic artery were evaluated based on the classification proposed by Michels’ in 1966. The findings was compared and correlated with operative data.

Results

Type I variant was seen in 43 patients (64.2) and variants were seen in other 24 patients (35.8%). We found seven patients with type II variant, 11 patients with type III variant, two patients with type V variant, and two patients with VI variant. There were two patients with type variants did not fit Michels’ classification. In 55 patients, the surgical findings concurred with 64 MDCT angiography findings (100%).

Conclusion

64 MDCT angiography is an effective, high-resolution, noninvasive imaging technique that readily demonstrates the hepatic arterial map with direct impact on treatment decisions including patient selection for hepatic resection.