Solid-phase synthesis of 4-biaryl-piperidine-4-carboxamides

A novel solid-phase synthesis of 4-biaryl-piperidine-4-carboxamides has been developed using FDMP resin with a carboxamide as the anchor point. With this approach, three points of diversity were incorporated into a GPCR-directed scaffold. Final products were obtained in good purity and yield.     

A new synthesis of 1,2,3,5‐tetrahydroimidazo[2,3‐b]‐[1,3]benzodiazocines

A new synthesis of 6‐carbomethoxy‐1,2,3,5‐tetrahydroirnidazo[2,3‐b][1,3]benzodiazocines 13 by the intramolecular cycloaddition reaction of methyl 2‐(1‐aziridinylmethyl)‐3‐(2‐ureidophenyl)propenoates 10 under Appel's dehydration conditions is described. The latter were readily obtained from 2‐nitrobenzalde‐hyde with methyl acrylate through the Baylis‐Hillman reaction.     

Superselection rules in quantum theory: Part I. A new proposal for state restriction violation

It is argued that preparation of a quantum state characterized by density operator not commuting with a superselection operatorQ does not by itself constitute an instance of superselection rule violation. It would, however, be an instance of state restriction violation. It is held that superselection rule violation is only possible with simultaneous observable and state restriction violations. It is shown that it is a priori conceivable to subdivide an ensemble whose satisfies[, Q] = 0 into subensembles whose density operators violate the state restrictions. The dynamics of the subdivision process is not considered.     

New information-theoretic foundations for quantum statistics

When the state of a physical system is not fully determined by available data, it should be possible nevertheless to make a systematic guess concerning the unknown state by applying the principles of information theory. The resulting theoretical blend of informational and mechanical constructs should then constitute a modern structure for statistical physics. Such a program has been attempted by a number of authors, most notably Jaynes, with seeming success. However, we demonstrated in a recent publication that the standard list of so-called mutually exclusive and exhaustive quantum states that is commonly employed by these authors is in fact not exhaustive. It follows that the information-theoretic foundations of quantum statistics must be reformulated. The present paper discusses the fundamental problems involved and establishes a format for the correct application of information theory to quantum mechanical situations.Work supported by a grant from Research Corporation.     

高能闪光照相中影响光程确定的几个因素

 利用闪光照相基本原理和成像原理，在直接记录法和转换屏记录法的情况下，研究了闪光照相中影响X射线在材料中光程确定的主要因素。结果表明，影响光程确定的几个因素是：散射效应、光源角分布效应、立体角效应和能谱效应。对于高能闪光照相，散射效应是影响光程确定的最主要因素，散射的存在使光程的测量值比实际值降低20%～40%。因此必须在做CT之前，对散射的影响进行修正。     

Intramitochondrial co-assembly between ATP and nucleopeptides induces cancer cell apoptosis

Mitochondria are essential intracellular organelles involved in many cellular processes, especially adenosine triphosphate (ATP) production. Since cancer cells require high ATP levels for proliferation, ATP elimination can be a unique target for cancer growth inhibition. We describe a newly developed mitochondria-targeting nucleopeptide (MNP) that sequesters ATP by self-assembling with ATP inside mitochondria. MNP interacts strongly with ATP through electrostatic and hydrogen bonding interactions. MNP exhibits higher binding affinity for ATP (−637.5 kJ mol⁻¹) than for adenosine diphosphate (ADP) (−578.2 kJ mol⁻¹). To improve anticancer efficacy, the small-sized MNP/ADP complex formed large assemblies with ATP inside cancer cell mitochondria. ATP sequestration and formation of large assemblies of the MNP/ADP–ATP complex inside mitochondria caused physical stress by large structures and metabolic disorders in cancer cells, leading to apoptosis. This work illustrates a facile approach to developing cancer therapeutics that relies on molecular assemblies.

Mitochondria-targeting nucleopeptide (MNP) can sequester ATP by self-assembling with ATP. A small nanosized MNP/ADP complex forms a large assembly with ATP. Thus, intramitochondrial co-assembly causes stress by large structures and apoptosis.     

An Upper Bound for the w-Weak Global Dimension of Pullbacks

Let R be a commutative ring with identity and I0 an ideal of R.We introduce and study the c-weak global dimension c-w.gl.dim(R/I0) of the factor ring R/I0.Let T be a w-linked extension of R,and we also introduce the wR-weak global dimension wR-w.gl.dim(T) of T.We show that the ring T with wR-w.gl.dim(T) =0 is exactly a field and the ring T with wR-w.gl.dim(T) ≤ 1 is exactly a PwRMD.As an application,we give an upper bound for the w-weak global dimension of a Cartesian square (RDTF,M).More precisely,if T is w-linked over R,then w-w.gl.dim(R) ≤ max{wR-w.gl.dim(T) + w-fdR T,c-w.gl.dim(D) + w-fdn D}.Furthermore,for a Milnor square (RDTF,M),we obtain w-w.gl.dim(R) ≤ max{wR-w.gl.dim(T) + w-fdR T,w-w.gl.dim(D) + w-fdR D}.     

Hepatoprotective Effects of Ixeris chinensis on Nonalcoholic Fatty Liver Disease Induced by High-Fat Diet in Mice: An Integrated Gut Microbiota and Metabolomic Analysis

Ixeris chinensis (Thunb.) Nakai (IC) is a folk medicinal herb used in Mongolian medical clinics for the treatment of hepatitis and fatty liver diseases even though its pharmacological mechanism has not been well characterized. This study investigated the hepatoprotective mechanism of IC on mice with nonalcoholic fatty liver disease (NAFLD) by integrating gut microbiota and metabolomic analysis. A high-fat diet (HFD) was used to develop nonalcoholic fatty liver disease, after which the mice were treated with oral IC (0.5, 1.5 and 3.0 g/kg) for 10 weeks. HFD induced NAFLD and the therapeutic effects were characterized by pathological and histological evaluations, and the serum indicators were analyzed by ELISA. The gut microbial and metabolite profiles were studied by 16S rRNA sequencing and untargeted metabolomic analysis, respectively. The results showed that the administration of IC resulted in significant decreases in body weight; liver index; serum biomarkers such as ALT, TG, and LDL-C; and the liver inflammatory factors IL-1β, IL-6, and TNF-α. The 16S rRNA sequencing results showed that administration of IC extract altered both the composition and abundance of the gut microbiota. Untargeted metabolomic analysis of liver samples detected a total of 212 metabolites, of which 128 were differentially expressed between the HFD and IC group. IC was found to significantly alter the levels of metabolites such as L-glutamic acid, pyridoxal, ornithine, L-aspartic acid, D-proline, and N4-acetylaminobutanal, which are involved in the regulation of glutamine and glutamate, Vitamin B6 metabolism, and arginine and proline metabolic pathways. Correlation analysis indicated that the effects of the IC extract on metabolites were associated with alterations in the abundance of Akkermansiaceae, Lachnospiraceae, and Muribaculaceae. Our study revealed that IC has a potential hepatoprotective effect in NAFLD and that its function might be linked to improvements in the composition of gut microbiota and their metabolites.