Sequential Transformation Research Articles

Effect of different antibiotic therapy in the treatment of patients with chronic pelvic inflammation disease and the influence on inflammatory factors

Objective To compare the effects of different antibiotic regimens on clinical efficacy and inflammatory factors in patients with chronic pelvic inflammatory disease. Methods 78 patients with chronic pelvic inflammatory disease were enrolled.They were randomly divided into observation group(antibiotic sequential method) and control group(sequential transformation of antibiotics) by computer generation test case random number method, 39 cases in each group.After treatment for 10 days, the clinical efficacy was observed, the serum IL-1 and IL-2 levels before and after treatment were compared.The economic costs, adverse events during the course of treatment were compared between the two groups, and 6 months after treatment, the recurrence was followed up in the two groups. Results After 10 days of treatment, the total effective rate was 94.59% in the observation group and 86.49% in the control group.The total remission rate in the observation group was higher than that in the control group(χ2=5.41, P=0.002). Before treatment, the levels of IL-1 and IL-2 of the observation group were (413.47±38.59)μg/L, (489.43±44.58)ng/L, respectively, which of the control group were (419.47±40.46)μg/L, (490.47±47.40)ng/L, respectively, and the differences were not statistically significant between the two groups (t=0.65, 0.10, P=0.52, 0.92). After treatment, the IL-1 level of the observation group[(288.53±32.48)μg/L] was lower than before treatment (t=15.07, P=0.00), and IL-2 level [(288.53±32.48)ng/L] was higher than before treatment (t=14.65, P=0.00). After treatment, the IL-1 level of the control group[(358.41±43.47)μg/L] was lower than before treatment (t=15.07, P=0.00), and IL-2 level [(550.46±32.90)ng/L] was higher than before treatment (t=14.65, P=0.00). The improvement of IL-1 and IL-2 levels in the observation group were better than those in the control group (t=7.83, 9.66, all P=0.00). The cost of drug and drug expense of the observation group were (115.47±3.48)RMB and (27.45±2.01)RMB, respectively, which of the control group were (120.45±3.39)RMB, (27.45±2.01)RMB, respectively, the differences between the two groups were not statistically significant (t=2.44, 0.00, P=0.17, 1.00). There were 2 cases with gastrointestinal discomfort in the observation group and 1 case in the control group, the difference between the two groups was not statistically significant (χ2=0.35, P=0.56). The adverse reactions of two groups were relatively minor, self-mitigation or disappeared after withdrawl the drug.After treatment for 6 months, the recurrence rate was 2.56%(1/39) in the observation group and 15.38%(6/39) in the control group.The recurrence rate of the observation group was lower than that of the control group(χ2=3.92, P=0.04). Conclusion The antibiotic sequential conversion therapy is the first intravenous antibiotics, and then oral combination, the recent and long-term clinical efficacy is good, and it is safe and reliable, without increasing the economic burden of patients, and is worthy of clinical use. Key words: Pelvic inflammatory disease; Anti-infective agents; Interleukins

Induction of Lymphangiomas by Freund's Incomplete Adjuvant (FIA) in Fatty Acid Binding Protein (FABP)‐3, 5 and 7 Knock‐out Mice

IntroductionIn an FIA‐induced benign lymphangioma model (Mancardi et al., 1999), we have suggested a sequential transformation from peritoneal mesothelial cells to functional lymphatic vessels via fat storing tumor cells after the FIA stimulation (EB2009 & 2015). However, the actual mechanism of the tumorigenesis and cellular involvement have yet to be established. FABPs are known to be involved in the promotion of cellular uptake and transport of fatty acids and the targeting of them to specific metabolic pathways. The aim of this study is, therefore, to investigate the possible involvement of FABPs during the FIA‐induced tumor development using FABP KO mice.Materials & MethodsLymphangiomas were induced in C57BL/6 (B6) mice and FABP3, 5 and 7 KO mice by an intraperitoneal injection of FIA (0.2 ml emulsion). For histological analyses, tissue cryosections were made and immunostained with various antibodies against FABP3, 4, 5, 7, and various lymphatic markers, such as podoplanin (PDPN), LYVE‐1 and LA102.Results & ConclusionsAfter FIA injection, peritoneal mesothelial cells became tall in height losing their polarity and gradually formed stratified cell masses on the peritoneal surface in B6 mice. The tumors became honeycomb‐like lymphangiomas consisted of ring‐like fat storing cells with various sizes. Some fat storing cells fused with each other and gradually formed either tubular structures like lymphatic vessels or huge follicles. These cells were strongly positive for PDPN, F4/80 and FABP5, but negative for FABP4. The follicular structures mainly consisted of FABP7+ cells. Interestingly, only the functional lymphatic vessel‐like structures expressed LYVE‐1 and LA102. In FABP‐KO mice, there was no significant difference in the incidence of tumors as compared with normal B6 mice. However, tumors developed more vigorously in FABP7 KO mice than other KO strains. Among FABP KO mice, relatively smaller fat storing cells were seen in FABP3 KO mice, whereas follicular type structures were more commonly found in FABP5 KO mice. In contrast, the tumors in FABP7 KO mice showed less fat storing cells with more inflammatory and fibrous components. In conclusion, a close relationship between the extrinsic FIA metabolism and the lymphatic system may be suggested in this tumor model, although the actual role and biological significance of each FABP in the tumorigenesis remain to be further clarified.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Site saturation mutagenesis of ribosomal protein L42 at 56th residue and application as a consecutive selection marker for cycloheximide resistance in yeast.

The 56th residue of ribosomal protein L42 (Rpl42) determines the sensitivity of yeast cells to the antibiotic cycloheximide (CYH). In this study, we identified the relationship between the 56th residue of Rpl42 and the function of the ribosome by site saturation mutagenesis. The resulting 20 RPL42 mutants harbouring one of 20 amino acids at the 56th residue were classified into five groups: sensitive to CYH (RPL42aP); weak resistance (RPL42aA, RPL42aM, RPL42aC, RPL42aN, RPL42aD, RPL42aS and RPL42aT), moderate resistance (RPL42aL, RPL42aI, RPL42aV, RPL42aG and RPL42aH), and strong resistance (RPL42aQ, RPL42aE, RPL42aR and RPL42aK) to CYH; and non-functional (RPL42aF, RPL42aY and RPL42aW). Three RPL42a mutants from each group, RPL42aA, RPL42aL and RPL42aQ, were used as CYH-resistant selection marker genes for the sequential transformation of CYH-sensitive yeast. A series of RPL42 mutants conferring different levels of resistance to CYH should be useful for the dose-dependent multiple selection of prototrophic industrial yeasts.

Optical orientation of nematic liquid crystal droplets via photoisomerization of an azodendrimer dopant

Two sequential transformations of the orientational structure in nematic liquid crystal droplets containing a dendrimer additive (nanosized macromolecules with light-absorbing azobenzene terminal moieties) under light irradiation in the UV–blue spectral range were investigated. The origin of these transitions is in the change of the boundary conditions due to photoisomerization of the dendrimer adsorbed onto the liquid crystal–glycerol interface. It was shown that the photoisomerization processes of dendrimer molecules in a liquid crystal are accompanied by a spatial rearrangement of their azobenzene moieties, which is the key point in the explanation of the observed effects.

Green and Efficient: Oxidation of Aldehydes to Carboxylic Acids and Acid Anhydrides with Air

An economic, safe, practical, and environmentally benign protocol for the oxidation of aldehydes to carboxylic acids and acid anhydrides with ambient air as the sole oxidant was developed. This oxidation is operationally simple and external catalyst-, initiator-, and base-free, with outstanding functional group tolerance (moisture-, acid-, base-, and oxidant-sensitive groups). It also provides a practical protocol for large scale synthesis (>100 g), late-stage modification of polyfunctional compounds, and one-pot sequential transformation starting from aldehydes.

Scalable total synthesis of horsfiequinone A

Starting from two commercially available substrates, methoxyhydroquinone and piperonyl alcohol, a scalable four-step total synthesis of horsfiequinone A was developed. The notable feature of the synthesis is the application of two continuous sequential transformations. Namely, the key aldehyde 9 and horsfiequinone A were prepared via scalable Wittig/hydrolysis and Wittig/catalytic hydrogenation/oxidation sequences, respectively. Importantly, the synthetic route required only three recrystallizations and one column chromatography purification step.

Sequential Transformation Behavior of Iron-Bearing Minerals during Underground Coal Gasification

Detailed mineralogical information from underground coal gasification (UCG) is essential to better understand the chemical reactions far below the surface. It is of great scientific significance to study the mineral transformation and identify the typical minerals in certain process conditions, because it may help to ensure the stable operation of gasification processes and improve the utilization efficiency of coal seams. The transformation of iron-bearing minerals has the typical characteristics during the UCG process and is expected to indicate the process parameters. In this paper, UCG progress was subdivided into pyrolysis, reduction and oxidation stages, and the progressive coal conversion products were prepared. Two types of lignite with different iron contents, Ulankarma and Ulanqab coals, were used in this study. The minerals in the coal transformation products were identified by X-ray diffraction (XRD) and a scanning electron microscope coupled with an energy-dispersive spectrometer (SEM-EDS). The thermodynamic calculation performed using the phase diagram of FactSage 7.1 was used to help to understand the transformation of minerals. The results indicate that the transformation behavior of iron-bearing minerals in the two lignites are similar during the pyrolysis process, in which pyrite (FeS2) in the raw coal is gradually converted into pyrrhotite (Fe1−xS). In the reduction stage, pyrrhotite is transformed into magnetite (Fe3O4) and then changes to FeO. The reaction of FeO and Al2O3 in the low iron coal produces hercynite above 1000 °C because of the difference in the contents of Si and Al, while in the high iron coal, FeO reacts with SiO2 to generate augite (Fe2Si2O6). When the temperature increases to 1400 °C, both hercynite and augite are converted to the thermodynamically-stable sekaninaite.

Silica‐Supported Molecular Catalysts for Tandem Reactions

AbstractThe development of silica‐supported molecular catalysts for tandem reactions is an important research direction of heterogeneous catalysis. Besides their significant merits in sustainable catalytic processes, numerous strategies have been utilized to construct silica‐supported molecular catalysts. Here, we emphasize tandem reactions and summarize the recent advances in sequential organic transformations. This paper is composed of four parts. The beginning part introduces silica as supports. The second part provides a large number of examples for the construction of non‐chiral molecular catalysts used for tandem reactions. The third part offers an outline for the construction of chiral molecular catalysts used for enantioselective tandem reactions. Finally, the perspectives for the further development of silica‐supported molecular catalysts for tandem reactions are addressed.

Ynesulfonamide‐Based Silica Gel and Alumina‐Mediated Diastereoselective Cascade Cyclizations to Spiro[indoline‐3,3′‐pyrrolidin]‐2‐ones under Neat Conditions

AbstractThe spiro[indoline‐3,3′‐pyrrolidin]‐2‐ones were synthesized via a silica gel and alumina‐mediated sequential transformation based on tryptamine‐derived ynesulfonamide substrates under neat conditions. The inherent tendency of C−C bond migration through Wagner‐Meerwein rearrangement in the synthesis of spirooxindole was prevented by water trapping to the spiroindoleninium intermediate. The functional group tolerances of the methodology were investigated using a variety of substrates. The detailed mechanism of the sequential transformation was probed by the isotope‐labeled experiments. This strategy was further applied in the formal syntheses of indole alkaloids coerulescine and horsfiline.magnified image

Kinetics of the electronic center annealing in Al2O3 crystals

The experimental annealing kinetics of the primary electronic F, F+ centers and dimer F2 centers observed in Al2O3 produced under neutron irradiation were carefully analyzed. The developed theory takes into account the interstitial ion diffusion and recombination with immobile F-type and F2-centers, as well as mutual sequential transformation with temperature of three types of experimentally observed dimer centers which differ by net charges (0, +1, +2) with respect to the host crystalline sites. The relative initial concentrations of three types of F2 electronic defects before annealing are obtained, along with energy barriers between their ground states as well as the relaxation energies.

Modular Synthesis of Dipyrroloquinolines: A Combined Synthetic and Mechanistic Study.

A straightforward synthesis of [1,2-a][3',2'-c]dipyrroloquinolines has been developed generating up to eight new σ-bonds and five new stereogenic centers in a simple and modular one-pot operation. Generally good to excellent yields and moderate to good stereoselectivities in favor of the all-cis stereoisomer were observed. A detailed investigation combining synthetic studies, analytical measurements, and theoretical calculations has been conducted to elucidate the reaction mechanism using ESI- and liquid-beam IR-laser desorption mass spectrometry as well as DFT calculations. Key steps of this sequential transformation include a Lewis acid-catalyzed vinylogous Mukaiyama-Mannich reaction of bis(silyl) dienediolate 1 and a Brønsted acid-promoted Mannich-Pictet-Spengler reaction cascade reaction to complete the synthesis of the dipyrroloquinoline core of the target compounds.

Maleimide and Cyclooctyne-Based Hexakis-Adducts of Fullerene: Multivalent Scaffolds for Copper-Free Click Chemistry on Fullerenes.

The synthesis of multivalent systems based on hexakis-adducts of [60]fullerene employing a biocompatible copper-free click chemistry strategy has been accomplished. A symmetric hexakis-adduct of fullerene bearing 12 maleimide units (3) is reported, and it has been employed to carry out the thiol-maleimide Michael addition. To achieve orthogonal click addition, an asymmetric derivative bearing one maleimide and 10 cyclooctynes has been synthesized. The sequential and one-pot transformations of the two clickable groups have been explored, finding the best results in the case of the one-pot experiment. This route has been used to obtain a biocompatible hexakis-adduct appended with two different biomolecules, carbohydrates, and amino acids.

Total Synthesis and Structural Determination of XR774, a Tyrosine Kinase Inhibitor.

Total synthesis and structural determination of XR774 has been accomplished. The benzo[ j]fluoranthene skeleton has been constructed by regioselective coupling between tetraline 3 and tetralone 4 successively followed by the sequential transformation including the Birch reduction to prepare allylic alcohol, simultaneous bromination of vinylic and aromatic moieties, and the nickel-mediated intramolecular coupling reaction. The optical resolution of racemic 17 led to the first total synthesis of (-)-XR774.

New multi-marker strains and complementing genes for Aspergillus nidulans molecular biology

Technical advances in Aspergillus nidulans enable relatively easy deletion of genomic sequences, insertion of sequences into the genome and alteration of genomic sequences. To extend the power of this system we wished to create strains with several selectable markers in a common genetic background to facilitate multiple, sequential transformations. We have developed an approach, using the recycling of the pyrG selectable marker, that has allowed us to create new deletions of the biA, pabaA, choA, and lysB genes. We have deleted these genes in a strain that carries the commonly used pyrG89, riboB2, and pyroA4 mutations as well as a deletion of the sterigmatocystin gene cluster and a deletion of the nkuA gene, which greatly reduces heterologous integration of transforming sequences. The new deletions are fully, easily and cheaply supplementable. We have created a strain that carries seven selectable markers as well as strains that carry subsets of these markers. We have identified the homologous genes from Aspergillus terreus, cloned them and used them as selectable markers to transform our new strains. The newly created strains transform well and the new deletion alleles appear to be complemented fully by the A. terreus genes. In addition, we have used deep sequencing data to determine the sequence alterations of the venerable and frequently used pyrG89, riboB2 and pyroA4 alleles and we have reannotated the choA gene.

An integrated immobilization strategy manipulates dual active centers to boost enantioselective tandem reactions.

Manipulation of dual active centers via an integrated immobilization strategy can overcome the restriction of homogeneous catalysis in a sequential organic transformation. Herein, by utilizing hollow-shell-structured silica, hydrogen-bonding immobilization via a ship-in-a-bottle synthesis locks a Pd(carbene) center in a nanocage and covalent-bonding immobilization tethers chiral Ru(diamine) centers within the nanochannels, constructing a hetero-bifunctional catalyst. The benefit of this dual center manipulation enables a challenging Suzuki coupling-asymmetric transfer hydrogenation tandem reaction, and the advantage of this process provides various chiral biarylols with enhanced reactivity and enantioselectivity.

Cellular Metabolism at a Glance.

Metabolism is highly coordinated component of the cellular activity that involves sequential chemical transformations, within a so-called metabolic network. Through these coordinated actions, living organisms acquire energy and biosynthetic precursors to maintain cellular homeostasis and function. Metabolism relies on the breaking down of macromolecules to produce energy [catabolism] and/or intermediary metabolites that are then used to construct essential building blocks for macromolecule production [anabolism]. Overall, these metabolic processes are controlled by cellular energy status: when the energy released from catabolic processes exceeds the cellular demands the storage of metabolites in the form of lipids and glycogen takes place. These phenomena have been vastly associated with the genesis of metabolic disorders, such as obesity. In recent years, we have assisted to a rediscovery of metabolism through the identification of metabolic intermediaries that act as key players on differentiation, proliferation, and function of immune cells. This recent acknowledgement of the impact of metabolism in the overall immune response originated the ground-breaking field of immunometabolism. Here, we will provide a holistic view of metabolism highlighting the biochemical principles underlying its regulation.

Copper-catalyzed domino sequences: a new route to pyrido-fused quinazolinones from 2'-haloacetophenones and 2-aminopyridines.

A new pathway to access pyrido-fused quinazolinones via a Cu(OAc)2-catalyzed domino sequential transformation between 2′-haloacetophenones and 2-aminopyridines was demonstrated. The solvent and base exhibited a remarkable effect on the transformation, in which the combination of DMSO and NaOAc emerged as the best system. Cu(OAc)2·H2O was more active towards the reaction than numerous other catalysts. This methodology is new and would be complementary to previous protocols for the synthesis of pyrido-fused quinazolinones.

Engineering Pichia pastoris for the Production of Carotenoids.

Carotenoids are one of the most diverse and widely distributed classes of pigments in the biosphere and exhibit a variety of functions in the nature. Their importance and biotechnological applications are higher and higher, but their sources are not increasing in the same exponential way. Here we describe the process of bioengineering the yeast Pichia pastoris by sequential transformation to get an astaxanthin producer.

Preparation of pyrrolizinone derivatives via sequential transformations of cyclic allyl imides: synthesis of quinolactacide and marinamide.

A facile synthetic route has been developed for the preparation of pyrrolizinone derivatives employing N-allyl imides as starting materials. The nucleophilic addition of a vinyl Grignard reagent/RCM/elimination sequence afforded pyrrolizinones in good yields and has been applied for the preparation of naturally occurring quinolactacide and marinamide.

Synthesis of Non-Conjugated Trienes via In Situ Hydrovinylation/Wittig Olefination of Unsaturated Phosphonium Salts

A cobalt-catalysed 1,4-hydrovinylation reaction is successfully applied in a sequential three-component transformation of unsaturated phosphonium bromides, 1,3-dienes, and aldehydes leading to non-conjugated products with a 1,4-diene subunit in good to excellent yields. The hydrovinylation provides regioselectively diene structures with one exo double bond whereas the third double bond can be introduced via an in situ Wittig or Horner–Wadsworth–Emmons olefination leading to 1,4,7-trienes suitable for further double bond functionalisations.