CircAGFG1 absence decreases PKM2 expression to enhance oxaliplatin sensitivity in colorectal cancer in a miR-7-5p-dependent manner.

Circular RNA (circRNA) ArfGAP with FG repeats 1 (circAGFG1) contributes to colorectal cancer (CRC) development. However, whether circAGFG1 regulates the resistance of CRC to oxaliplatin (L-OHP) remains unknown. CircAGFG1, microRNA-7-5p (miR-7-5p) and pyruvate kinase M2 (PKM2) RNA expression were quantified by quantitative real-time polymerase chain reaction.

Fast heritability estimation based on MINQUE and batch training.

Heritability, the proportion of phenotypic variance explained by genome-wide single nucleotide polymorphisms (SNPs) in unrelated individuals, is an important measure of the genetic contribution to human diseases and plays a critical role in studying the genetic architecture of human diseases. Linear mixed model (LMM) has been widely used for SNP heritability estimation, where variance component parameters are commonly estimated by using a restricted maximum likelihood (REML) method. REML is an iterative optimization algorithm, which is computationally intensive when applied to large-scale datasets (e.

A review of SNP heritability estimation methods.

Over the past decade, statistical methods have been developed to estimate single nucleotide polymorphism (SNP) heritability, which measures the proportion of phenotypic variance explained by all measured SNPs in the data. Estimates of SNP heritability measure the degree to which the available genetic variants influence phenotypes and improve our understanding of the genetic architecture of complex phenotypes. In this article, we review the recently developed and commonly used SNP heritability estimation methods for continuous and binary phenotypes from the perspective of model assumptions and parameter optimization.

Insights into the N-Heterocyclic Carbene (NHC)-Catalyzed Oxidative γ-C(sp)-H Deprotonation of Alkylenals and Cascade [4 + 2] Cycloaddition with Alkenylisoxazoles.

The N-heterocyclic carbene (NHC)-catalyzed oxidative C-H deprotonations have attracted increasing attention; however, the general mechanism regarding this kind of oxidative organocatalysis remains unclear. In this paper, the competing mechanisms and origin of the stereoselectivity of the NHC-catalyzed oxidative γ-C(sp)-H deprotonation of alkylenals and cascade [4 + 2] cycloaddition with alkenylisoxazoles were systematically investigated for the first time using density functional theory (DFT). The computed results indicate that the oxidation of the Breslow intermediate by 3,3',5,5'-tetra- tert-butyl diphenoquinone (DQ) via a hydride transfer to oxygen (HTO) pathway is the most favorable among the four competing pathways.

Insights into the N-Heterocyclic Carbene (NHC)-Catalyzed Intramolecular Cyclization of Aldimines: General Mechanism and Role of Catalyst.

One of the most challenging questions in the Lewis base organocatalyst field is how to predict the most electrophilic carbon for the complexation of N-heterocyclic carbene (NHC) and reactant. This study provides a valuable case for this issue. Multiple mechanisms (A, B, C, D, and E) for the intramolecular cyclization of aldimine catalyzed by NHC were investigated by using density functional theory (DFT).

Computational Study on γ-C-H Functionalization of α,β-Unsaturated Ester Catalyzed by N-Heterocyclic Carbene: Mechanisms, Origin of Stereoselectivity, and Role of Catalyst.

The N-heterocyclic carbene (NHC)-catalyzed γ-C-H deprotonation/functionalization of α,β-unsaturated esters with hydrazones leading to the δ-lactams has been theoretically investigated by using density functional theory. Three possible reaction mechanisms including Mechanism A, for which the NHC catalyst serves as a nucleophilic catalyst to attack on the carbonyl carbon atom to initiate the reaction, Mechanism B, in which NHC triggers the reaction through the hydrogen bond, and Mechanism C, which is the direct deprotonation/functionalization process without the presence of NHC, have been suggested and studied in detail. The most favorable Mechanism A was identified to proceed through the following processes: nucleophilic attack on the carbonyl carbon of the ester by NHC, γ-deprotonation, formal [4 + 2] cycloaddition of dienolate with hydrazone, and regeneration of NHC.

Density functional theory study on structure and stability of BeB clusters.

Rationale: Boride compounds hold promise for broad applications in the field of optoelectronics due to their high-temperature resistant, corrosion resistant and antioxidant properties. In order to reveal the formation mechanism of alkali and alkaline earth metal doped boron clusters, theoretical studies of these systems are required.

Methods: All the possible geometrical structures of BeB clusters (n = 1-8) were optimized at the B3LYP/6-311+G(d) level; the harmonic vibration frequencies were obtained to examine the true stability and give the zero-point vibration energy at that theoretical level.

Water sandwiched by a pair of aromatic rings in a proton-conducting metal-organic framework.

The interactions between water molecules and aromatic rings are known to be common and important in physics, chemistry and life sciences. Benzene-water complexes are the main prototype systems for O-Hπ and lone-pair (lp)π interactions in theoretical research, however solid state examples are very rare. Here, the solid state example of water sandwiched by a pair of aromatic rings is observed in a silver-mellitate framework, where lpπ and O-Hπ interactions coexist.

A Lightweight Social Computing Approach to Emergency Management Policy Selection.

In order to select effective policies for emergency management in a timely manner, this paper proposes an agile and lightweight social computing approach to facilitating policy selection, evaluation, and adjustment relative to emergency management in both quantitative and qualitative ways. The approach consists of three components represented as PZE: 1) (P) emergency management policy selecting; 2) (Z) modeling artificial societies with the zombie-city model (a general and formal artificial society model); and 3) (E) policy evaluation. The formal specification of the zombie-city model and rigorous expressions of scenarios enable rigorous description and formal reasoning of an artificial society.

A computational study on the N-heterocyclic carbene-catalyzed Csp(2)-Csp(3) bond activation/[4+2] cycloaddition cascade reaction of cyclobutenones with imines: a new application of the conservation principle of molecular orbital symmetry.

A comprehensive density functional theory (DFT) investigation has been performed to interrogate the mechanisms and stereoselectivities of the Csp(2)-Csp(3) single bond activation of cyclobutenones and their [4+2] cycloaddition reaction with imines via N-heterocyclic carbene (NHC) organocatalysis. According to our calculated results, the fundamental reaction pathway contains four steps: nucleophilic addition of NHC to cyclobutenone, C-C bond cleavage for the formation of an enolate intermediate, [4+2] cycloaddition of the enolate intermediate with isatin imine, and the elimination of the NHC catalyst. In addition, the calculated results also reveal that the second reaction step is the rate-determining step, whereas the third step is the regio- and stereo-selectivity determining step.

Energetics and kinetics of Cu atoms and clusters on the Si(111)-7 × 7 surface: first-principles calculations.

Exploring the properties of noble metal atoms and nano- or subnano-clusters on the semiconductor surface is of great importance in many surface catalytic reactions, self-assembly processes, crystal growth, and thin film epitaxy. Here, the energetics and kinetic properties of a single Cu atom and previously reported Cu magic clusters on the Si(111)-(7 × 7) surface are re-examined by the state-of-the-art first-principles calculations based on density functional theory. First of all, the diffusion path and high diffusion rate of a Cu atom on the Si(111)-(7 × 7) surface are identified by mapping out the total potential energy surface of the Cu atom as a function of its positions on the surface, supporting previous experimental hypothesis that the apparent triangular light spots observed by scanning tunneling microscopy (STM) are resulted from a single Cu atom frequently hopping among adjacent adsorption sites.

A DFT study on NHC-catalyzed intramolecular aldehyde-ketone crossed-benzoin reaction: mechanism, regioselectivity, stereoselectivity, and role of NHC.

A systematic theoretical study has been carried out to understand the mechanism and stereoselectivity of N-heterocyclic carbene (NHC)-catalyzed intramolecular crossed-benzoin reaction of enolizable keto-aldehyde using density functional theory (DFT) calculations. The calculated results reveal that the most favorable pathway contains four steps, i.e.

Insights into Stereoselective Aminomethylation Reaction of α,β-Unsaturated Aldehyde with N,O-Acetal via N-Heterocyclic Carbene and Brønsted Acid/Base Cooperative Organocatalysis.

A theoretical investigation has been performed to interrogate the mechanism and stereoselectivities of aminomethylation reaction of α,β-unsaturated aldehyde with N,O-acetal, which is initiated by N-heterocyclic carbene and Brønsted acid (BA). The calculated results disclose that the reaction contains several steps, i.e.

A DFT study on PBu3-catalyzed intramolecular cyclizations of N-allylic substituted α-amino nitriles for the formation of functionalized pyrrolidines: mechanisms, selectivities, and the role of catalysts.

The mechanisms and chemo- and stereo-selectivities of PBu3-catalyzed intramolecular cyclizations of N-allylic substituted α-amino nitriles leading to functionalized pyrrolidines (5-endo-trig cyclization, Mechanism A) and their competing reaction leading to another kind of pyrrolidine (5-exo-trig cyclization, Mechanism B) have been investigated using density functional theory (DFT). Multiple possible reaction pathways associated with four different isomers (RR, SR, RS, and SS) for Mechanism A, and two isomers (R and S) for Mechanism B have been studied. The calculated results indicate that the Gibbs free energy barriers of Mechanism A are remarkably lower than those of Mechanism B, and the reaction pathway leading to the RS-configured product has the lowest Gibbs free energy barrier, which is in agreement with the experiments.

Theoretical studies on binding modes of copper-based nucleases with DNA.

In the present work, molecular simulations were performed for the purpose of predicting the binding modes of four types of copper nucleases (a total 33 compounds) with DNA. Our docking results accurately predicted the groove binding and electrostatic interaction for some copper nucleases with B-DNA. The intercalation modes were also reproduced by "gap DNA".

DFT Study on the Mechanism and Stereoselectivity of NHC-Catalyzed Synthesis of Substituted Trifluoromethyl Dihydropyranones with Contiguous Stereocenters.

Recently, Smith and co-workers reported an interesting work that provides a facile approach to access substituted trifluoromethyl dihydropyranones with two contiguous stereocenters by utilizing the α,β-unsaturated trifluoromethyl ketones as a substrate for NHC-catalyzed [4 + 2] cycloadditions. The most significant point of this reaction lies in the capability of introducing substituents to the C(5) position of the dihydropyranones. In the present study, we performed detailed DFT investigations toward the catalytic mechanism of this reaction, and determined origins of the diastereo- and enatioselectivities through analyses on distortion energies of two key stationary species and on components of Gibbs free energy barriers of elementary steps in which the stereocenters are generated.

Do Practical Standard Coupled Cluster Calculations Agree Better than Kohn-Sham Calculations with Currently Available Functionals When Compared to the Best Available Experimental Data for Dissociation Energies of Bonds to 3d Transition Metals?

Coupled-cluster (CC) methods have been extensively used as the high-level approach in quantum electronic structure theory to predict various properties of molecules when experimental results are unavailable. It is often assumed that CC methods, if they include at least up to connected-triple-excitation quasiperturbative corrections to a full treatment of single and double excitations (in particular, CCSD(T)), and a very large basis set, are more accurate than Kohn-Sham (KS) density functional theory (DFT). In the present work, we tested and compared the performance of standard CC and KS methods on bond energy calculations of 20 3d transition metal-containing diatomic molecules against the most reliable experimental data available, as collected in a database called 3dMLBE20.

Theoretical Investigations toward the Asymmetric Insertion Reaction of Diazoester with Aldehyde Catalyzed by N-Protonated Chiral Oxazaborolidine: Mechanisms and Stereoselectivity.

In recent years, the N-protonated chiral oxazaborolidine has been utilized as the Lewis acid catalyst for the asymmetric insertion reaction, which is one of the most challenging topics in current organic chemistry. Nevertheless, the reaction mechanism, stereoselectivity, and regioselectivity of this novel insertion reaction are still unsettled to date. In this present work, the density functional theory (DFT) investigation has been performed to interrogate the mechanisms and stereoselectivities of the formal C-C/H insertion reaction between benzaldehyde and methyl α-benzyl diazoester catalyzed by the N-protonated chiral oxazaborolidine.

Fundamental reaction pathway and free energy profile of proteasome inhibition by syringolin A (SylA).

In this study, molecular dynamics (MD) simulations and first-principles quantum mechanical/molecular mechanical free energy (QM/MM-FE) calculations have been performed to uncover the fundamental reaction pathway of proteasome with a representative inhibitor syringolin A (SylA). The calculated results reveal that the reaction process consists of three steps. The first step is a proton transfer process, activating Thr1-O(γ) directly by Thr1-N(z) to form a zwitterionic intermediate.

Mechanisms and stereoselectivities of the Rh(I)-catalyzed carbenoid carbon insertion reaction of benzocyclobutenol with diazoester.

In this study, a density functional theory (DFT) study has been carried out to investigate the mechanisms of Rh(I)-catalyzed carbenoid carbon insertion into a C-C bond reaction between benzocyclobutenol (R1) and diazoester (R2). The calculated results indicate that the reaction proceeds through five stages: deprotonation of R1, cleavage of the C-C bond, carbenoid carbon insertion, intramolecular aldol reaction, and protonation of the alkoxyl-Rh(I) intermediate. We have suggested and studied two possible pathways according to different coordination patterns (including ketone-type and enol-type coordination forms) in the fourth stage and found that the enol-type pathway is favorable, making the coordination mode of the Rh(I) center in the oxa-π-allyl Rh(I) intermediate clear in this reaction system.

Self-assembly of an unprecedented polyoxomolybdate anion [Mo20O66]12- in a giant peanut-like 62-core silver-thiolate nanocluster.

A polyoxometalate-templated silver thiolate nanocluster, [Ag62(S(t)Bu)40(Mo20O66)(Mo6O19)3(CH3CN)2]·(CF3SO3)4 (1), has been isolated, in which a giant peanut-like silver(i)-thiolate cluster [Ag62(S(t)Bu)40](22+) encapsulates an unprecedented [Mo20O66](12-) polyoxoanion core. It opens a new approach for the synthesis of both elusive polyoxometalates and high-nuclearity silver(i)-thiolate nanoclusters.

A highly sensitive C3-symmetric Schiff-base fluorescent probe for Cd2+.

A new C3-symmetric Schiff-base fluorescent probe (L) based on 8-hydroxy-2-methylquinoline has been developed. As expected, the probe L can display high fluorescent selectivity for Cd(2+) over Zn(2+) and most other common ions in neutral ethanol aqueous medium. Moreover, the mechanism of the L-Cd(2+) complex has been confirmed by X-ray crystallography and density functional theory calculation results.

A DFT study on the reaction mechanism of dimerization of methyl methacrylate catalyzed by N-heterocyclic carbene.

Reaction mechanisms of the N-heterocyclic carbene (NHC)-catalyzed dimerization of methyl methacrylate were studied using density functional theory (DFT) at the M05-2X/6-31G(d,p) level of theory. Four possible reaction channels (A, B, C, and D) have been investigated in this work. Particularly, we proposed a novel reaction pathway, where the proton transfers are assisted by a different molecule.

Highly enantioselective catalytic system for asymmetric copolymerization of carbon dioxide and cyclohexene oxide.

A new ligand can be easily prepared, and its intramolecular dinuclear zinc complexes act as a high performance catalyst for the asymmetric alternating copolymerization of cyclohexene oxide and CO2 under very mild conditions (1 atm CO2 , room temperature), affording completely alternating polycarbonates with up to 93.8 % enantiomeric excess (ee) and 98 % yield. A high Mn value of 28 600 and a relatively narrow polydispersity (Mw /Mn ratio) of 1.

A new fluorescent probe for Al(3+) based on rhodamine 6G and its application to bioimaging.

A water-soluble rhodamine-based derivative (L) has been rationally designed for selective recognition of Al(3+) in aqueous medium with good sensitivity. The addition of Al(3+) to the aqueous solution of L induces a remarkable fluorescence enhancement along with obvious color change detected by the naked eye, due to the ring-opening mechanism of the rhodamine spirolactam, which has been proved by single crystal diffraction analyses directly. The recognizing behavior has been investigated both experimentally and computationally.