Increasing evidence indicates that various cancer cell types are capable of producing IgG. The exact function of cancer-derived IgG has, however, not been elucidated. Here we demonstrated the expression of IgG genes with V(D)J recombination in 80 cases of colorectal cancers, 4 colon cancer cell lines and a tumor bearing immune deficient mouse model. IgG expression was associated with tumor differentiation, pTNM stage, lymph node involvement and inflammatory infiltration and positively correlated with the expressions of Cyclin D1, NF-κB and PCNA. Furthermore, we investigated the effect of cancer-derived IgG on the malignant behaviors of colorectal cancer cells and showed that blockage of IgG resulted in increased apoptosis and negatively affected the potential for anchor-independent colony formation and cancer cell invasion. These findings suggest that IgG synthesized by colorectal cancer cells is involved in the development and growth of colorectal cancer and blockage of IgG may be a potential therapy in treating this cancer.

Density functional theory (DFT) calculations were used to study the mechanism for the cleavage reaction of the RNA analogue HpPNP (HpPNP = 2-hydroxypropyl-4-nitrophenyl phosphate) catalyzed by the dinuclear Zn(II) complex of 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn(2)(L(2)O)). We present a binding mode in which each terminal phosphoryl oxygen atom binds to one zinc center, respectively, and the nucleophilic 2-hydroxypropyl group coordinates to one of the zinc ions, while the hydroxide from deprotonation of a water molecule coordinates to the other zinc ion. Our calculations found a concerted mechanism for the HpPNP cleavage with a 16.5 kcal/mol reaction barrier. An alternative proposed stepwise mechanism through a pentavalent oxyphosphorane dianion reaction intermediate for the HpPNP cleavage was found to be less feasible with a significantly higher energy barrier. In this stepwise mechanism, the deprotonation of the nucleophilic 2-hydroxypropyl group is accompanied with nucleophilic attack in the rate-determining step. Calculations of the nucleophile (18)O kinetic isotope effect (KIE) and leaving (18)O KIE for the concerted mechanism are in reasonably good agreement with the experimental values. Our results indicate a specific-base catalysis mechanism takes place in which the deprotonation of the nucleophilic 2-hydroxypropyl group occurs in a pre-equilibrium step followed by a nucleophilic attack on the phosphorus center. Detailed comparison of the geometric and electronic structure for the HpPNP cleavage reaction mechanisms in the presence/absence of catalyst revealed that the catalyst significantly altered the determining-step transition state to become far more associative or tight, that is, bond formation to the nucleophile was remarkably more advanced than leaving group bond fission in the catalyzed mechanism. Our results are consistent with and provide a reliable interpretation for the experimental observations that suggest the reaction occurs by a concerted mechanism (see Humphry, T.; Iyer, S.; Iranzo, O.; Morrow, J. R.; Richard, J. P.; Paneth, P.; Hengge, A. C. J. Am. Chem. Soc. 2008, 130, 17858-17866) and has a specific-base catalysis character (see Yang, M.-Y.; Iranzo, O.; Richard, J. P.; Morrow, J. R. J. Am. Chem. Soc. 2005, 127, 1064-1065).

A recent success in which the engineered iron-haem enzymes P411CHA′ aminate the intermolecular benzylic C–H bond with both high efficiency and stereoselectivity solves a long-standing challenge in synthetic chemistry (Nat. Chem.20179629634). The mechanism, reactivity, and stereoselectivity of this reaction were studied by quantum mechanical (QM)/molecular mechanical (MM) calculations in this work. To understand better the origin of such an excellent catalytic performance of biocatalyst P411CHA′, iron-cofactor FePIX alone for the intermolecular C–H bond amination was also theoretically investigated as a comparison. The catalytic cycle includes two processes: N2 dissociation and nitrene transfer. The calculation results show that P411CHA′ enzyme can catalyze intermolecular C–H amination with high reactivity and stereoselectivity, whereas the FePIX-catalyzed reaction has much higher barriers for both N2 dissociation and nitrene transfer compared to P411CHA′. The reason for this dramatic difference in catalytic reactivity between P411CHA′ and FePIX is that the former but not the latter allows the formation of precursors B- 5 PR1 and B- 3 PR2, which are structurally close to transition states B- 3 TS1 and B- 3 TS2 and accelerate N2 dissociation and nitrene transfer, respectively. The mutated residues (A82L A78V F263L) assist the formations of B- 5 PR1 and B- 3 PR2 via reducing effectively the size of the haem distal pocket. High stereoselectivity of P411CHA′ stems from the steric effect in H-abstraction. A theoretical analysis on how para substituent R affects reactivity was also carried out. A strong π-type electron-donating group on the substrate enhances significantly the reactivity of P411CHA′-catalyzed intermolecular C–H amination. These results provide valuable information for designing and constructing environmentally friendly biocatalytic C–H amination systems with high reactivity and stereoselectivity.

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Theoretical studies on 6,6‘-disubstitution effects of the dpq in [Ru(bpy)2(dpq)]2+ are carried out by using DFT method at the B3LYP/LanL2DZ level. The substituent effects caused by the electron-pushing group (OH) and the electron-withdrawing group (F) on the electronic structures and the related properties, e.g., the energies and the components of some frontier molecular orbitals, the spectral properties, and the net charge populations of some main atoms of the complexes, etc., have been investigated. The computational results show that the substituents have some interesting effects on the electronic structures and related properties of the complexes. First, on the basis of the analysis of the frontier molecular orbitals, the substituents influence the first excited-state properties of the substitutive derivates. The electron-withdrawing group (F) can activate the main ligand and passivate the co-ligands in the first excited state of [Ru(bpy)2(2F-dpq)]2+, whereas the electron-pushing group (OH) does not have this effect in this system. Second, the ground band wavelength of electronic spectra of each of complexes [Ru(bpy)2(2R-dpq)]2+ (R = OH, H, or F) is shorter slightly than that of well-known complex Ru(bpy)3 2+. The substitution of electron-pushing group (OH) or electron-withdrawing group (F) on 6,6‘ sites of dpq in [Ru(bpy)2(dpq)]2+ can cause a slight red shift in the ground band of the complex. Third, some interesting characteristics of atomic net charge populations on the main ligands of the three complexes occur, and they can be simply and satisfactorily interpreted applying the schematic map expressed by several series of arrowheads, based on the law of polarity alternation and the idea of polarity interference. The above theoretical results should be important to further inquiry into the interaction mechanism of the complexes with DNA active units from both the molecular orbital interactions and the atomic charge interactions.

MicroRNAs (miRNAs) are small noncoding RNAs, which downregulate gene expression by repressing or degrading mRNA targets. Lung cancer (LC), together with liver and colorectal cancers are the three leading causes of cancer death worldwide, and 80% of LCs belong to non-small cell lung cancers (NSCLCs). Despite a great advancement in developing distinct and delicate tools for early diagnosis and targeted therapies over the last decade, only about 15% of the NSCLC patients eventually survived. MiRNAs are frequently dysregulated in carcinoma, including LC. Numerous lines of evidence have demonstrated various roles played by miRNAs in the development and progression of LC. In this review, we propose to summarize the current understanding of miRNAs in LC, with a particular focus on translational application of miRNAs as novel diagnostic and prognostic biomarkers and tools for treatment.

The theoretical studies on a series of isoelectronic complexes M(bpy) 3 n+ (M ) Re, Os, and Ir; n ) 1, 2, and 3, respectively) are carried out with DFT method at B3LYP/LanL2DZ level. The electronic structures and related chemical properties of complexes M(bpy) 3 n+ , in particular, the regularities of the center ionic effects on the spectral properties, the chemical stabilities, and the atomic net charge populations, have been investigated. The results show that, for the complexes Re(bpy) 3 1+ and Os(bpy) 3 2+ , the main components of HOMO and NHOMO come from d orbitals of the center ion, but for the LUMO and NLUMO, the main components come from p orbitals of the atoms C and N in ligands. Therefore, the ground bands and the next ground bands of their electronic spectra are designed as a typical spectrum band of the singlet metal-to-ligand charge transfer ( 1 MLCT). Whereas for the complex Ir(bpy) 3 3+ , whether HOMO and NHOMO or LUMO and NLUMO, their main components come from the p orbitals of C and N in ligands, so the ground band and the next ground band of its electronic spectra are designed as a typical band of the singlet ligand-to-ligand transition ( 1 Lπ-π*). With increase of the atomic number of the center atom M, the energy interval between HOMO and LUMO increases, the wavelength of the corresponding spectrum decreases, and the chemical stability of the complex increases. In addition, for three complexes, there are more negative charge populations on C6 in the ligands, and then C6 can be expected as an active site in electrophilic reactions. The computational results can be better used to explain some experimental phenomena and regularities.

The genus Helicobacter is a group of Gram-negative, helical-shaped pathogens consisting of at least 36 bacterial species. Helicobacter pylori (H. pylori), infecting more than 50% of the human population, is considered as the major cause of gastritis, peptic ulcer, and gastric cancer. However, the genetic underpinnings of H. pylori that are responsible for its large scale epidemic and gastrointestinal environment adaption within human beings remain unclear. Core-pan genome analysis was performed among 75 representative H. pylori and 24 non-pylori Helicobacter genomes. There were 1173 conserved protein families of H. pylori and 673 of all 99 Helicobacter genus strains. We found 79 genome unique regions, a total of 202,359bp, shared by at least 80% of the H. pylori but lacked in non-pylori Helicobacter species. The operons, genes, and sRNAs within the H. pylori unique regions were considered as potential ones associated with its pathogenicity and adaptability, and the relativity among them has been partially confirmed by functional annotation analysis. However, functions of at least 54 genes and 10 sRNAs were still unclear. Our analysis of protein-protein interaction showed that 30 genes within them may have the cooperation relationship.