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Tuberculosis, caused by mycobacteria, continues to pose a substantial public health threat. Mycobacteria typically use cholesterol from the membranes of host macrophages as a carbon and energy source. Most genes that control cholesterol degradation are regulated by KstR, which is highly conserved in Mycobacterium tuberculosis and Mycobacterium smegmatis. Through bioinformatic analysis, we found a typical global nitrogen regulator (GlnR)-binding motif (CCGAC-AACAGT-GACAC) in the promoter region of kstR of M. smegmatis, and we determined its binding activity in vitro using electrophoretic mobility shift assays. Using RT-qPCR, we found that nine genes involved in side-chain or sterol-ring oxidation were upregulated in a ΔglnR M. smegmatis strain compared to the WT strain and glnR-complemented strains under nitrogen limitation. ATP assays in macrophages revealed that coordinated GlnR-KstR regulation significantly reduced the viability of M. smegmatis in macrophages. Thus, we found that various genes involved in cholesterol catabolism are regualted by GlnR via KstR in response to environmental nitrogen, and that they further affect the invasive ability of M. smegmatis. These findings revealed a novel regulatory mechanism of cholesterol catabolism, which may be useful in the development of new strategies for controlling tuberculosis. This article is protected by copyright. All rights reserved.

Magnetic coordination complexes based on Schiff bases are promising new molecular materials for electronics. Two μ-oxo FeIII dimeric complexes of enantiomers of Schiff base ligands (N,N′-(1R,2R)-1,2-diphenylethylenebis(salicylideneimine) (H2salphen-R, 1 a) and N,N′-(1S,2S)-1,2-diphenylethylenebis(salicylideneimine) (H2salphen-S, 1 b)) were synthesized; further reaction with 4-salicylideneamino-1,2,4-triazole (Hsaltrz) led to enantiomers of two one-dimensional (1D) FeIII coordination complexes. The structures of these complexes were determined by X-ray diffraction. Magnetic susceptibility measurements revealed that μ-oxo dimeric complexes displayed strong antiferromagnetic coupling, whereas the 1D complexes exhibited paramagnetic behavior. The chirality of the Schiff bases transferred to macromolecular chirality of the complexes, which could be monitored by both vibrational and electronic circular dichroism (CD) spectroscopic methods. The macroscopic handedness was manifested in CD signals attributed to exciton coupling between the ligands. Thus, the chiral spectroscopies were useful to probe the chirality of the complexes, their structure, and the polymerization degree.

Aim Clinical studies have shown that statin use may modify the risk of kidney cancer. However, these studies yielded different results. To quantify the association between statin use and risk of kidney cancer, we performed a detailed meta-analysis of published studies regarding this subject. Methods A literature search was carried out using MEDLINE, EMBASE and the Cochrane database between January 1966 and October 2012. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Fixed effect and random effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also performed. Results A total of 12 (two randomized controlled trials, five cohort, and five case–control) studies contributed to the analysis. There was heterogeneity among the studies but no evidence of publication bias. Pooled results indicated a non-significant decrease of total kidney cancer risk among all statin users (RR = 0.92, 95% CI 0.71, 1.19). Long term statin use did not significantly affect the risk of total kidney cancer (RR = 1.01, 95% CI 0.83, 1.22). In our subgroup analyses, the results were not substantially affected by study design, confounder adjustment and gender. Furthermore, sensitivity analysis confirmed the stability of the results. Conclusion The findings of this meta-analysis suggested that there was no association between statin use and risk of kidney cancer. More studies, especially randomized controlled trials and high quality cohort studies with larger sample size and well controlled confounding factors, are needed to confirm this association in the future.

Two couples of enantiomeric platinum(II) complexes: Pt(L1a)Cl (1a), Pt(L1b)Cl (1b) and Pt(L1a)(C ≡ C − Ph) (2a), Pt(L1b)(C ≡ C − Ph) (2b) (L1a = (+)-1,3-di-(2-(4,5-pinene)pyridyl)benzene, L1b = (−)-1,3-di-(2-(4,5-pinene)pyridyl)benzene) were synthesized and characterized. Their absolute configurations were determined by single crystal X-ray diffraction and further verified by circular dichroism (CD) spectra (including electronic circular dichroism [ECD] and vibrational circular dichroism [VCD]). These complexes show interesting mechanoluminescence and/or vapoluminescence due to crystalline-to-amorphous transformation. The crystalline solids, grinding-induced amorphous powders, and vapor-induced amorphous powders of complexes 2a and 2b were comparatively investigated by solid-state ECD and VCD spectra. The transformation from crystalline solids to amorphous powders was accompanied by significant variances of the spectral feature in both ECD and VCD spectra. Chirality 25:384–392, 2013. © 2013 Wiley Periodicals, Inc.

Novel copper(II) coordination compounds with chiral macrocyclic imine ligands derived from R-/S-camphor were asymmetrically synthesized and characterized with the aid of chiroptical spectroscopies. Crystal structures of both enantiomers were determined by single crystal X-ray diffraction analysis. Circular dichroism (CD) spectra were analyzed using a simplified exciton model as well as quantum chemical computations. The absolute configuration of the copper(II) coordination compounds determined from CD was found consistent with the crystal data. The copper(II) complexes were further investigated by vibrational CD (VCD) measurement combined with density functional theory calculation. The complex formation was evidenced by spectral shifts of the characteristic bands in the CD and VCD spectra. Chirality 24:451–458, 2012. © 2012 Wiley Periodicals, Inc.

Background Although the role of peri-operative chemotherapy is established in the treatment of locally advanced gastric cancer, the optimal regime remains to be determined. FOLFOX has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established. Methods This is a prospective non-randomized study comparing peri-operative FOLFOX versus adjuvant FOLFOX in patients with resectable locally advanced gastric cancer. Response to chemotherapy was assessed according to WHO criteria and pathological changes. Kaplan–Meier log rank test was used to calculate and compare survival differences. Results There were 73 patients (neoadjuvant = 36). Complete and partial response was observed in 2 (6%) and 21 (64%) patients, respectively. Four-year overall survival (OS) in the neoadjuvant arm was 78% versus 51% in the adjuvant arm (P = 0.031). Subgroup analysis found R0 resection (86% vs. 55%, P = 0.011) and patients with proximal cancers (87% vs. 14%, P

A series of three-way catalysts (TWCs), containing a small amount of precious metals (PMs, including Pt, Pd and Rh) and a large amount of promoters CeO2 and La2O3, were prepared with different precursor compounds and various doped manners. Crystal phases, dispersion of cerium and lanthanum, textural structure and thermal stability of the catalysts were investigated by XRD, XPS and pore parameters determination. The catalytic performance was studied by the measurements of CO, C3H6 and NO conversions on dependence of temperature at stoichimetric number point (S = 1.00), and from S = 0.75 to 1.30 at 280°C or 340°C for fresh or aged samples, respectively. The correlation between the catalytic performance and the characteristics of fresh and aged samples were discussed. The results show mat the sample, in which CeO2 and La2O3 are doped with mixed oxide powders, possesses poor dispersion and less thermal stability, and the conversions of NO and C3H6 are apparently lower man those of the samples aged at 850°C The main reason is due to the lanthanum enrichment on the surface. The precious metals and cerium may be covered and enveloped, and the PMs located on the internal microporous surface where no cerium and lanthanum exist, are easier to sinter and oxidize. For the sample doped with La(NO3)3 and Ce(NO3)3 aqueous solutions, high dispersion and thermal stable CeO2-La2O3 solid solution on all the surface of microporous γ-Al2O3 is identified. The solid solution CeO2La2O3 also possessed high dispersion in Ok sample doped with La2O3 powder and Ce(NO3)3 aqueous solution. The last two aged samples keep higher NO conversion at S≥1 region.

Rapidly separating genepin-crosslinked gelatin (RS-GC) microneedles (MNs) mounted on the polyvinyl alcohol (PVA)-coated polylactic acid (PLA) MNs (RS-PGC-MNs) are fabricated, in which GC-MNs deliver insulin within the skin and the PLA supporting array is easily separated by the dissolution of the PVA layer. The release of insulin is controlled by utilizing the virtue of genipin as a crosslinking agent for producing biocompatible GC-MNs. The degree of crosslinking enhances the mechanical strength as well as humidity resistance. The in vitro and in vivo insulin release tests show significant changes in the release rates in the RS-PGC-MNs with different crosslinking degree. The hypoglycemic effect in diabetic mice demonstrate that the higher crosslinking GC-MNs result in characteristic controlled insulin release compared with other treatments and prolonged effectiveness of the RS-PGC-MNs. The proposed RS-PGC-MNs is a promising device for effective use as a noninvasive and painless controlled insulin delivery system.

Two eudesmane sesquiterpene lactones, wedetrilides B (1) and C (2), along with five known analogues (3 - 8), an ent-kaurane diterpenoid (9), a steroid (10), as well as cinnamic acid derivatives (11 - 13), were isolated from the flowers of Wedelia trilobata. Their structures were elucidated on the basis of extensive spectroscopic analyses and by comparison of their NMR data with those of related compounds. Furthermore, the structures of 1 and 3 - 5 were confirmed by X-ray single-crystal diffraction analyses. Compounds 4 and 5 exhibited weak cytotoxic activities against the MCF-7, HeLa, and A549 cell lines. Compounds 3 - 5 were also evaluated for their inhibitory effects against HIV lytic replication.

Cellular memory is a ubiquitous phenomenon in cell biology. Using numerical simulation and theoretical analysis, we explored the robustness of cellular memory to intrinsic noise in a transcriptional positive feedback system. Without noise, the system could create two stable steady states and function as a memory module. Memory robustness index and mean first-passage time were used to quantify the robustness of memory. Large cell size and strong cooperativity in binding enhanced memory storage remarkably. Adding a second positive feedback loop improved persistent memory significantly, whereas including a negative one destabilized memory storage. These are consistent with experimental observations. We interpret why positive feedback loops are actively involved in epigenetic memory from a dynamical systems perspective.

A velocity imaging technique combined with (2+1) resonance-enhanced multiphoton ionization (REMPI) is used to detect the primary Br((2)P(3/2)) fragment in the photodissociation of o-, m-, and p-dibromobenzene at 266 nm. The obtained translational energy distributions suggest that the Br fragments are produced via two dissociation channels. For o- and m-dibromobenzene, the slow channel that yields an anisotropy parameter close to zero is proposed to stem from excitation of the lowest excited singlet (pi,pi*) state followed by predissociation along a repulsive triplet (n,sigma*) state localized on the C-Br bond. The fast channel that gives rise to an anisotropy parameter of 0.53-0.73 is attributed to a bound triplet state with smaller dissociation barrier. For p-dibromobenzene, the dissociation rates are reversed, because the barrier for the bound triplet state becomes higher than the singlet-triplet crossing energy. The fractions of translational energy release are determined to be 6-8 and 29-40 % for the slow and fast channels, respectively; the quantum yields are 0.2 and 0.8, and are insensitive to the position of the substituent. The Br fragmentation from bromobenzene and bromofluorobenzenes at the same photolyzing wavelength is also compared to understand the effect of the number of halogen atoms on the phenyl ring.

The velocity imaging technique combined with (2+1) resonance-enhanced multiphoton ionization (REMPI) is used to detect the halogen fragments in the photodissociation of bromobenzene and iodobenzene at 266 nm. With the aid of potential energy curve calculations by Lunell (Y. J. Liu, P. Persson, S. Lunell, J. Phys. Chem. A 2004, 108, 2339-2345.), the Br fragmentation is proposed to stem from excitation of the lowest excited singlet (pi - pi*) state followed by predissociation along a repulsive triplet (n - sigma*) state. The slowed dissociation rate leads to production of the isotropic Br fragments and 93% internal energy deposition. Only the ground state Br(P-2(3/2)) is detectable. In contrast, when iodine is substituted, the iodine effect stabilizes the repulsive states associated with the I-C6H5 bond rupture and the subsequent dissociation channels become more complicated. 84% of the iodobenzene molecules obtained follow a direct dissociation channel, while the remaining undergo a predissociative process. Both routes result in rapid dissociation with anisotropy parameters of 0.7 +/- 0.2 and 0.9 +/- 0.2 as well as 70% and 26% in the fractions of translational energy deposition, respectively. The relative quantum yields of 1* and 1 are 0.35 and 0.65 and their related photodissociation pathways are discussed in detail.

This is the protocol for a review and there is no abstract. The objectives are as follows: We propose to determine the sensitivity, specificity and diagnostic odds ratio (DOR) of magnetic resonance imaging (MRI) and computed tomography (CT) for detecting lymph node metastasis in patients with preoperative rectal cancer and specifically to determine which one is the optimal radiologic modality for the diagnosis of lymph node metastasis. We propose to identify the test which has the higher sensitivity and acceptable DOR as the optimal test. We also plan to estimate the difference in diagnostic accuracy for lymph node metastasis between patients with and without preoperative chemotherapy and/or radiation therapy.