依达拉奉联合醒脑静治疗急性脑出血的临床疗效观察

目的:探究依达拉奉联合醒脑静治疗急性脑出血(ACH)的临床疗效及对炎症指标的影响。方法:本研究于2013年2月~2015年2月期间,选择我院收治的ACH患者128例为研究对象,采用随机数字法将其分为研究组(65例)和对照组(63例)。两组患者均给予一般常规治疗并给予依达拉奉,研究组患者在此基础上联用醒脑静注射液治疗。观察两组患者治疗前后炎症因子变化、采用美国国立卫生研究院的卒中量表(NIHSS)评价神经功能缺损修复情况、采用格拉斯哥昏迷评分(GCS)评价患者意识状态,并对比治疗后临床疗效。结果:治疗后两组患者C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平和NIHSS评分均出现明显降低(均P0.05),GCS评分均出现明显升高(P0.05),且研究组上述指标改善均优于对照组,差异均存在统计学差异(均P0.05);治疗后研究组有效率为87.69%,显著高于对照组的69.84%(X2=6.125,P=0.013)。结论:依达拉奉联合醒脑静治疗ACH,能够改善患者神经功能损伤及炎症反应,预后好,疗效确切,具有重要的临床价值。     

外源硝态氮水平对长春花生理代谢的影响

以长春花为实验材料,采用珍珠岩为培养基质,设置不同氮素浓度,对其各器官的初生和次生代谢进行了初步研究,结果如下:植株中3种主要生物碱含量均是随着外源氮水平的降低而降低,外源硝态氮水平对长春花文朵灵和长春质碱在不同叶位叶片中的积累特点影响较明显,而对长春碱的积累影响较小。在高氮条件下,植物体内合成和积累较高水平的游离氨基酸,可能为部分生物碱的合成提供了骨架,并能促进生物碱含量的提高。蔗糖含量在不同叶位叶片中也是随着叶龄的增加而缓慢增加。同时,高氮水平下,叶片中蔗糖含量明显高于正常供氮水平下的含量。本研究为提高长春花中具有重要药用价值生物碱的含量提供参考依据。     

QM/MM investigation of the catalytic mechanism of angiotensin-converting enzyme

Angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II and degrades bradykinin and other vasoactive peptides. ACE inhibitors are used to treat diseases such as hypertension and heart failure. It is thus highly desirable to understand the catalytic mechanism of ACE, as this should facilitate the design of more powerful and selective ACE inhibitors. ACE exhibits two different active domains, the C-domain and the N-domain. In this work, we systematically investigated the inhibitor- and substrate-binding patterns in the N-domain of human ACE using a combined quantum mechanical and molecular mechanical approach. The hydrolysis of hippuryl–histidyl–leucine (HHL) as catalyzed by the N-domain of human somatic ACE was explored, and the effects of chloride ion on the overall reaction were also investigated. Two models, one with and one without a chloride ion at the first binding position, were then designed to examine the chloride dependence of inhibitor–substrate binding and the catalytic mechanism. Our calculations indicate that the hydrolysis reaction follows a stepwise general base/general acid catalysis path. The estimated mean free energy barrier height in the two models is about 15.6 kcal/mol, which agrees very well with the experimentally estimated value of 15.8 kcal/mol. Our simulations thus suggest that the N-domain is in a mixed form during ACE-catalyzed hydrolysis, with the single-chloride-ion and the double-chloride-ion forms existing simultaneously.

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Graphical Abstract Superposition of ACE C- and N- domains

     

Reexamination of structures,stabilities, and electronic properties of holmium-doped silicon clusters HoSi<Subscript><Emphasis Type="Italic">n</Emphasis></Subscript> (<Emphasis Type="Italic">n</Emphasis> = 12–20)

The total energies, growth patterns, equilibrium geometries, relative stabilities, hardnesses, intramolecular charge transfer, and magnetic moments of HoSi _n (n?=?12–20) clusters have been reexamined theoretically using two different density functional schemes in combination with relativistic small-core Stuttgart effective core potentials (ECP28MWB) for the Ho atoms. The results show that when n?=?12–15, the most stable structures are predicted to be exohedral frameworks with a quartet ground state, but when n?=?16–20, they are predicted to be endohedral frameworks with a sextuplet ground state. These trend in stability across the clusters (gauged from their dissociation energies) was found to be approximately the same regardless of the DFT scheme used in the calculations, with HoSi₁₃, HoSi₁₆, HoSi₁₈, and HoSi₂₀ calculated to be more stable than the other clusters. The results obtained for cluster hardness indicated that doping the Ho atom into Si₁₃ and Si₁₆ leads to the most stable HoSi _n clusters, while doping Ho into the other Si _n clusters increases the photochemical sensitivity of the cluster. Analyses of intracluster charge transfer and magnetic moments revealed that charge always shifts from the Ho atom to the Si _n cluster during the creation of exohedral HoSi _n (n?=?12–15) structures. However, the direction of charge transfer is reversed during the creation of endohedral HoSi _n (n?=?16–20) structures, which implies that Ho acts as an electron acceptor when it is encapsulated in the Si _n cage. Furthermore, when the most stable exohedral HoSi _n (n?=?12–15) structures are generated, the 4f electrons of Ho are virtually unchanged and barely participate in intracluster bonding. However, in the most stable endohedral HoSi _n (n?=?16–20) frameworks, a 4f electron does participate in bonding. It does this by transferring to the 5d orbital, which hybridizes with the 6s and 6p orbitals and then interacts with Si valence sp orbitals. Meanwhile, the total magnetic moments of the HoSi _n (n?=?16–20) clusters are considerably higher than those of HoSi _n (n?=?12–15). Interestingly, the endohedral HoSi₁₆ and HoSi₂₀ clusters can be viewed as the most suitable building blocks for novel high-density magnetic storage nanomaterials and for novel optical and optoelectronic photosensitive nanomaterials, respectively.     

Effects of the adsorption of alkali metal oxides on the electronic,optical, and thermodynamic properties of the Mg<Subscript>12</Subscript>O<Subscript>12</Subscript>nanocage: a density functional theory study

The effect of alkali metal oxides M _n O (M?=?Li, Na, K; n?=?2, 3, 4) on the geometric, electronic, and linear and nonlinear optical properties of the Mg₁₂O₁₂ nanocage was investigated by density-functional-based methods. According to the computational results, these alkali metal oxides are adsorbed on the Mg₁₂O₁₂ nanocage because this adsorption reduces its energy gap. The static first hyperpolarizability (β ₀) of the nanocage is dramatically increased in the presence of the alkali metal oxides, with the greatest increase seen in the presence of the superalkalis (i.e., M₃O; M?=?Li, Na, and K). The highest first hyperpolarizability (β ₀?≈?600,000 a.u.) was calculated for K₃O@Mg₁₂O₁₂, which was considerably more than that for Mg₁₂O₁₂. The thermodynamic properties and relative stabilities of these inorganic compounds are discussed.

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Graphical Abstract Optimized structure and DOS spectrum of K₃O(e@Mg₁₂O₁₂)

     

Molecular dynamics simulations of the orientation properties of cytochrome <Emphasis Type="Italic">c</Emphasis> on the surface of single-walled carbon nanotubes

Electron transfer between cytochrome c (Cytc) and electrodes can be influenced greatly by the orientation of protein on the surface of the electrodes. In the present study, different initial orientations of Cytc on the surface of five types of single-walled carbon nanotubes (SWNTs), with different diameters and chirality, were constructed. Properties of the orientations of proteins on the surface of these tubes were first investigated through molecular dynamics simulations. It was shown that variations in SWNT diameter do not significantly affect the orientation; however, the chirality of the SWNTs is crucial to the orientation of the heme embedded in Cytc, and the orientation of the protein can consequently be influenced by the heme orientation. A new electron pathway between Cytc and SWNT, which hopefully benefits electron transfer efficiency, has also been proposed. This study promises to provide theoretical guidance for the rational design of bio-sensors or bio-fuel cells by using Cytc-decorated carbon nanotube electrodes.     

Examination of the quality of various force fields and solvation models for the equilibrium simulations of GA88 and GB88

Elucidating the relationship between sequence and conformation is essential for the understanding of functions of proteins. While sharing 88 % sequence identity and differing by only seven residues, GA88 and GB88 have completely different structures and serve as ideal systems for investigating the relationship between sequence and function. Benefiting from the continuous advancement of the computational ability of modern computers, molecular dynamics (MD) simulation is now playing an increasingly important role in the study of proteins. However, the reliability of MD simulations is limited by the accuracy of the force fields and solvent model approximations. In this work, several AMBER force fields (AMBER03, AMBER99SB, AMBER12SB, AMBER14SB, AMBER96) and solvent models (TIP3P, IGB5, IGB7, IGB8) have been employed in the simulations of GA88 and GB88. The statistical results from 19 simulations show that GA88 and GB88 both adopt more compact structures than the native structures. GB88 is more stable than GA88 regardless of the force fields and solvent models utilized. Most of the simulations overestimated the salt bridge interaction. The combination of AMBER14SB force field and IGB8 solvent model shows the best overall performance in the simulations of both GA88 and GB88. AMBER03 and AMBER12SB also yield reasonable results but only in the TIP3P explicit solvent model.     

Altered torquoselectivity of fluorine in the iron-tricarbonyl-mediated thermal ring opening of 3-fluorocyclobutene: a density-functional exploration

There are eight possible pathways for the iron-tricarbonyl-assisted thermal electrocyclic ring opening of fluorocyclobutene due to variations in the orientation of the binding of Fe(CO)₃ relative to the fluorine substituent (R₁ or R₂), stereoselectivity (conrotatory or disrotatory, i.e., C or D), and the torquoselectivity of fluorine (inward-facing or outward-facing, i.e., in or out). A density functional study revealed that the energetically favored pathway is R₁ Din. Not only is the D mode favored energetically, but the in configuration was observed to be the lowest-lying mode of R₁, despite the general tendency of fluorine substituents to prefer an out configuration. Data on the activation hardness and aromaticity indices such as BAC and HOMA lead to the same conclusion. However, the R₂ mode surprisingly shows no particular preference for either the Cout or the Dout pathway (i.e., the R₂ mode shows less stereoselectivity than R₁). This behavior occurs due to the influences of both the fluorine substituent and metal coordination. Also, the geminal bond orbitals σ(C–F) and σ*(C–F) appear to participate in ring opening, given the excellent correlation of ?BE with the activation barrier of the transition state.