Developing prognostic nomograms to predict overall survival and cancer-specific survival in synchronous multiple primary colorectal cancer based on the SEER database.

BACKGROUND: Synchronous multiple primary colorectal cancer (SMPCC) is a rare subtype of CRC, characterized by the presence of two or more primary CRC lesions simultaneously or within 6 months from the detection of the first lesion. We aim to develop a novel nomogram to predict OS and CSS for SMPCC patients using data from the SEER database. METHODS: The clinical variables and survival data of SMPCC patients between 2004 and 2018 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Appropriate inclusion and exclusion criteria were established to screen the enrolled patients. Univariate and multivariate Cox regression analyses were used to identify the independent risk factors for OS and CSS. The performance of the nomogram was evaluated using the concordance index (C-index), calibration curves, and the area under the curve (AUC) of a receiver operating characteristics curve (ROC). A decision curve analysis (DCA) was generated to compare the net benefits of the nomogram with those of the TNM staging system. RESULTS: A total of 6772 SMPCC patients were enrolled in the study and randomly assigned to the training (n = 4670) and validation (n = 2002) cohorts. Multivariate Cox analysis confirmed that race, marital status, age, histology, tumor position, T stage, N stage, M stage, chemotherapy, and the number of dissected LNs were independent prognostic factors.The C-index values for OS and CSS prediction were 0.716 (95% CI 0.705-0.727) and 0.718 (95% CI 0.702-0.734) in the training cohort, and 0.760 (95% CI 0.747-0.773) and 0.749 (95% CI 0.728-0.769) in the validation cohort. The ROC and calibration curves indicated that the model had good stability and reliability. Decision curve analysis revealed that the nomograms provided a more significant clinical net benefit than the TNM staging system. CONCLUSION: We developed a novel nomogram for clinicians to predict OS and CSS, which could be used to optimize the treatment in SMPCC patients.

Removal and transformation of polycyclic aromatic hydrocarbons during electrocoagulation treatment of an industrial wastewater.

Polycyclic aromatic hydrocarbons (PAHs) are an important class of water pollutants because of their known ecological and human toxicity. Electrocoagulation (EC) is a promising technology for mitigating industrial wastewater pollution, but the removal and transformation of PAHs during EC treatment has not yet been understood. Therefore, a paper-making wastewater effluent (PMWW) was employed in this study to investigate the relationship between PAHs' removal and transformation during EC treatment. The results show that 86% of PAHs were effectively removed not only by the electro-oxidation reactions, but also by adsorption onto Fe hydroxide flocs. The removal and transformation of PAHs were related to the number of rings in their structures. Some PAHs composed of two aromatic rings (e.g., naphthaline and dimethylnaphthalene) were produced from humic acid-like and fulvic acid-like organics in PMWW, while PAHs with three to four rings were degraded, thus being removed efficiently. Therefore, PAH transformation during EC treatment exerted double-sided effects on the removal of PAHs; the net effect appeared to be positive. Overall, this study revealed the existence and importance of PAH transformation during EC treatment and provided useful guidance for pulp and paper mills to improve the design and operation of wastewater treatment facilities.

Design and Synthesis of a New Series of 4-Heteroarylamino-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octanes as α7 Nicotinic Receptor Agonists. 1. Development of Pharmacophore and Early Structure-Activity Relationship.

The design and synthesis of a series of quinuclidine-containing spirooxazolidines ("spiroimidates") and their utility as α7 nicotinic acetylcholine receptor partial agonists are described. Selected members of the series demonstrated excellent selectivity for α7 over the highly homologous 5-HT3A receptor. Modification of the N-spiroimidate heterocycle substituent led to (1S,2R,4S)-N-isoquinolin-3-yl)-4'H-4-azaspiro[bicyclo[2.2.2]octane-2,5'oxazol]-2'-amine (BMS-902483), a potent α7 partial agonist, which improved cognition in preclinical rodent models.

Remote safety monitoring for elderly persons based on omni-vision analysis.

Remote monitoring service for elderly persons is important as the aged populations in most developed countries continue growing. To monitor the safety and health of the elderly population, we propose a novel omni-directional vision sensor based system, which can detect and track object motion, recognize human posture, and analyze human behavior automatically. In this work, we have made the following contributions: (1) we develop a remote safety monitoring system which can provide real-time and automatic health care for the elderly persons and (2) we design a novel motion history or energy images based algorithm for motion object tracking. Our system can accurately and efficiently collect, analyze, and transfer elderly activity information and provide health care in real-time. Experimental results show that our technique can improve the data analysis efficiency by 58.5% for object tracking. Moreover, for the human posture recognition application, the success rate can reach 98.6% on average.

Conformationally constrained ortho-anilino diaryl ureas: discovery of 1-(2-(1'-neopentylspiro[indoline-3,4'-piperidine]-1-yl)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea, a potent, selective, and bioavailable P2Y1 antagonist.

Preclinical antithrombotic efficacy and bleeding models have demonstrated that P2Y1 antagonists are efficacious as antiplatelet agents and may offer a safety advantage over P2Y12 antagonists in terms of reduced bleeding liabilities. In this article, we describe the structural modification of the tert-butyl phenoxy portion of lead compound 1 and the subsequent discovery of a novel series of conformationally constrained ortho-anilino diaryl ureas. In particular, spiropiperidine indoline-substituted diaryl ureas are described as potent, orally bioavailable small-molecule P2Y1 antagonists with improved activity in functional assays and improved oral bioavailability in rats. Homology modeling and rat PK/PD studies on benchmark compound 3l will also be presented. Compound 3l was our first P2Y1 antagonist to demonstrate a robust oral antithrombotic effect with mild bleeding liability in the rat thrombosis and hemostasis models.

Discovery and optimization of (R)-prolinol-derived agonists of the Growth Hormone Secretagogue receptor (GHSR).

The discovery and optimization of a novel series of prolinol-derived GHSR agonists is described. This series emerged from a 11,520-member solid-phase library targeting the GPCR protein superfamily, and the rapid optimization of low micromolar hits into single-digit nanomolar leads can be attributed to the solid-phase synthesis of matrix libraries, which revealed multiple non-additive structure-activity relationships. In addition, the separation of potent diastereomers highlighted the influence of the alpha-methyl stereochemistry of the phenoxyacetamide sidechain on GHSR activity.

Conformationally restricted homotryptamines 3. Indole tetrahydropyridines and cyclohexenylamines as selective serotonin reuptake inhibitors.

A series of indole tetrahydropyridine and indole cyclohexenylamines was prepared, and their binding affinities at the human serotonin transporter (SERT) were determined. In particular, a nitrile substituent at the C5 position of the indole ring gave potent SERT activity. The stereochemistry of the N,N-dimethylamine substituent was determined for the most potent indole cyclohexenylamine, 6a. The enantiomers of 6a were energy minimized and compared to other conformationally restricted SSRIs. Compound 6a was found to give a dose-response similar to the SSRI fluoxetine in microdialysis studies in rats.

A metal-organic framework material that functions as an enantioselective catalyst for olefin epoxidation.

A new microporous metal-organic framework compound featuring chiral (salen)Mn struts is highly effective as an asymmetric catalyst for olefin epoxidation, yielding enantiomeric excesses that rival those of the free molecular analogue. Framework confinement of the manganese salen entity enhances catalyst stability, imparts substrate size selectivity, and permits catalyst separation and reuse.

Microporous pillared paddle-wheel frameworks based on mixed-ligand coordination of zinc ions.

The reaction of Zn(NO3)2 x 6H2O, various dicarboxylic acids, and either 4,4'-bipyridine or N,N'-di(4-pyridyl)-1,4,5,8-naphthalenetetracarboxydiimide produces a family of anisotropic, mixed-ligand, open-framework compounds featuring paddle-wheel-type coordination of Zn(II) pairs in two dimensions and pyridyl ligand pillaring in the third. Despite 2-fold interpenetration, the compounds contain channels of molecular dimensions and several are permanently microporous, displaying high internal surface areas.

Observation of an octameric water cluster containing a book-shaped hexamer in a 4f-3d complex.

An octameric water cluster consisting of a book-shaped water hexamer and two dangling water molecules has been observed in a 4f-3d ionic pair complex [Y(dpdo)2(H2O)4][Co(CN)6].4H2O.

Assembly of hydrogen bonded diamondoid networks based on synthetic metal-organic tetrahedral nodes.

Reaction of Mn(ClO4)2 or Co(PF6)2 with 4,4'-dipyridine-dioxide (dpdo) produced novel molecular species [M(dpdo)4(H2O)2]2+, which hold a tetrahedral configuration notwithstanding their octahedral environment around the metal centers. The tetrahedral moieties are further assembled through hydrogen bonds between peripheral NO ends of dpdo ligands and coordinated water molecules, giving rise to 3D diamondoid networks.

Cyclic water pentamer in a tape-like structure.

A novel water tape consisting of fused cyclic water pentamers has been observed in a supramolecular compound.

Symmetry induced supramolecular assembly of a resorcinarene trimeric molecular box.

A novel trimeric resorcinarene molecular box is induced during hydrothermal synthesis by use of the 3-fold symmetric tripyridyl triazine linker molecule.

Structure and photoluminescence of a benzil nanocolumn in a C-methylcalix[4]resorcinarene-based framework.

A new framework based on C-methylcalix[4]resorcinarene and the flexible nonconjugated spacer 1,4-bis(imidazol-1yl-methyl)benzene encloses a large one-dimensional channel, containing benzil nanocolumns. Unlike in a previously reported series of benzil-containing supramolecular solids with conjugated linker molecules, benzil luminescence is observed, but the lifetime of 580 ns at 77 K is considerably shorter than the 145 micros reported for neat benzil at room temperature.

Multiple conformations of benzil in resorcinarene-based supramolecular host matrixes.

Six supramolecular complexes incorporating benzil as a guest, CMCR*bipy*benzil (alpha) 1 (CMCR = C-methylcalix[4]resorcinarene), CMCR*bipy*benzil (beta) 2, CMCR*2bpe*benzil*ethanol 3 (bpe = trans-1,4-bis(pyridyl)ethylene), CMCR*2bpe*benzil*2H2O 4, CMCR.2bpeh*benzil*ethanol 5 (bpeh = bis-(1-pyridin-4-yl-ethylidene)-hydrazine), and CECR*2bpe.benzil 6 (CECR = C-ethylcalix[4]resorcinarene), have been synthesized by hydrothermal and conventional methods and characterized by X-ray diffraction. Resorcinarene adopts a boat conformation in 1-4 and a bowl conformation in 5 and 6. Compounds 1-4 show a brick-wall-like framework, in which two benzil molecules are incorporated. For 5, bpeh spacers link CMCR molecules to give a one-dimensional wavelike polymer in which one benzil guest is embedded within the polymer cavity. Complex 6 forms a carcerand-like capsule in which two benzil guests are encapsulated. The O=C-C=O torsion angles vary from 91.8 to 139.3 degrees and correlate with the length of the central C-C bond. The benzil concentration, which is approximately 6.2 mol/L in the neat crystals, varies between 1.01 and 1.51 mol/L in the structures studied, corresponding to a 6-fold dilution. The benzil molecules are disordered in the larger cavities of 4 and 5. The two benzoyl fragments are almost perpendicular in 3, which has the next largest cavity size when solvent volume is excluded, whereas a nearly trans-coplanar conformation occurs for the cavity with the smallest volume in 6.

Formation of pyrene nano-rods within a supramolecular framework.

The combination of trimesic acid and the tri-dentate linker 1,3,5-tri(4-pyridyl)-2,4,6-triazine leads to the assembly of a bilayer structure, which contains four pyrene molecules per cavity; adjacent tetrameric aggregates within the channels formed by the superimposed layers combine to yield pyrene nano-rods.

The design and synthesis of a non-centric diamond-like network based NH4+ ion.

Two novel acentric hydrogen bonded two-dimensional sheet and three-dimensional 2-fold interpenetrating diamond-like networks have been designed and prepared based on a tetrahedral ammonium node and the O,O'-bifunctional linker molecules dipyridine dioxide (dpdo) and trans-bis(4-pyridyl)ethylene dioxide (bpedo).

Long-range ferromagnetic ordering in two-dimensional coordination polymers Co[N(CN)2]2(L) [L = pyrazine dioxide (pzdo) and 2-methyl pyrazine dioxide (mpdo)] with dual mu- and mu3-[N(CN)2] bridges.

Two novel coordination polymers of Co(II) with dicyanamide (dca) were obtained by the addition of ancillary ligands of pyrazine dioxide (pzdo) and 2-methyl pyrazine dioxide (mpdo) into the Co-dca binary system, respectively. Co[N(CN)(2)](2)(pzdo) (1) crystallizes in the orthorhombic space group of Pnnm (No. 58) with a = 9.4699(5) A, b = 14.9984(3) A, c = 7.4313(7) A, and Z = 4, while Co[N(CN)(2)](2)(mpdo) (2) is in the monoclinic space group C2 (No. 5) with a = 16.5391(4) A, b = 9.6065(2) A, c = 7.5001(2) A, beta = 105.779(1) degrees, and Z = 4. Both complexes contain similar two-dimensional triangular Co-dca layers, which offer rare examples of mixed 1,5-mu- and mu(3)-dca bridging coordination polymers with long-range ferromagnetic ordering below ca. 2.5 K.

Three-fold interpenetrating three-dimensional networks based on C-methylcalix[4]resorcinarene incorporating benzophenone guest molecules.

A new solid based on C-methylcalix[4]resorcinarene and the linker molecule bis(4-pyridylmethylidyne)hydrazine (bpmh) has been prepared, in which brick-wall sheets are linked in the third dimension to give networks with three intersecting perpendicular channels; the networks interpenetrate three-fold, but nevertheless leave cavities capable of including sizable guest molecules.