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Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2+CD9+subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1+and PLVAP+endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFRα+collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis.

1.The kinetics of alkaline and neutral aqueous hydrolysis of ethyl esters of substituted alkylphosphonic acids was studied.2.On the basis of a correlation analysis of data on the hydrolysis of phosphonates and phosphinates the contribution of the inductive effect and pp - dp conjugation of the ethoxyl group at phosphorus to the free energy of activation was evaluated.

1.The kinetics of reactions with water and OH- ions for esters of chloroalkylphosphonic and bis-(chloroalkyl) phosphinic acids with various positions of chlorine in the molecule was investigated.2.In the reaction with water for esters possessing chlorine in the ?-position, there is an unusual increase in the rate of hydrolysis, which can be explained by the intramolecular influence of chlorine on the reaction center.3.The different behavior of the esters in the reactions with water and the OH- ion is evidently due to a change in the reaction center. The nature of the influence of chlorine on the reaction center during intramolecular catalysis is discussed.

1.The kinetics of hydrolysis of N,N'-tetramethyl-N'',N?-tetraethyltetraamidopyrophosphate was studied in solutions of hydrochloric acid (from 1 to 11.6 M). The rate constant of hydrolysis, as a function of the HC1 concentration, possesses a maximum. The observed activation energy does not depend upon the HC1 content.2.Hydrolysis of the substrate is irreversible and includes several successive steps. The final products of hydrolysis are alkylamines and phosphoric acid. The limiting step of the process is interaction of the protonized form of the substrate with water.

1.The kinetics of the hydrolysis of pyrophos in aqueous dioxane solutions was studied. The first-order rate constants k1 were determined at various compositions of the mixed solvent and temperatures.2.The influence of a change in the polarity of the medium and solvation upon the reaction rate was analyzed. The basic influence upon the reaction rate is exerted by a change in the solvation of pyrophos, associated with a change in the composition of the medium.

1.The rate constants of the hydrolysis of pyrophos and tetraethyl pyrophosphate in water at a number of temperatures, as well as the rate constants of the hydrolysis of pyrophos in KOH and hydrochloric acid medium, were determined.2.It was established according to the dependence of the observed rate constant on the acidity of the medium that the limiting step in the acid hydrolysis is decomposition of the protonated form of pyrophos.

1.The kinetics of the alkaline and neutral aqueous hydrolysis of a number of phosphinic esters was investigated, and the rate constants and parameters of the Arrhenius equation were determined.2.The rate constants of the reactions with water and the OH- ion are correlated with the sum of Taft s* constants, as well as with the sum of the Kabachnik constants tf for the substituents at the phosphorus.3.The secondary butyl ester of bis(chloromethyl)phosphinic acid has an unusually high rate of hydrolysis in the reaction with ester, which is explained by the SN1 mechanism for this ester.

1.The rate constants of hydrolysis were determined for a number of bis(chloromethyl)phosphinic esters in aqueous dioxane solutions at various compositions and temperatures.2.For the investigated compounds the reaction rate in a mixed solvent is not described by the Kirwood and Winstein-Grunwald equations; however, there is a linear relationship between the logarithm of the rate constant of hydrolysis and the activity of water.3.The sec-butyl ester of bis(chloromethyl)phosphinic acid is hydrolyzed according to an SN1 mechanism.

Summary The investigation demonstrated that an iron, nickel, and zinc hydroxide mixture of the required composition can be prepared electrolytically. The resultant system can readily be converted into an oxide mixture and used for ferrite manufacture. By using hydrochloric acid solutions as electrolytes, it is possible to deposit hydroxide mixtures of high purity and to eliminate washing, which is time consuming and requires a large quantity of distilled water.

An increased reactivity of esters of acetylmethyl- and carboxymethylphosphonic acids in a spontaneous hydrolysis and of esters of acetylalkylphosphonic acids in alkaline hydrolysis as the result of intramolecular catalysis has been established. Enol forms of the esters participate in the mechanisms of the intramolecular catalysis.

1.The rate constants and parameters of the Arrhenius equation were determined for alkaline and neutral aqueous hydrolysis ofa-substituted dialkylphosphinic esters of phenol.2.The reactivity decreases as thea-substituents at the alkyl radicals are changed in the series Cl > Br>I> CH3.3.The rate constants of both reactions are correlated with the Taft induction constants s* of the substituents at the phosphorus.4.The mechanism of hydrolysis reactions is discussed.

A study was made of the kinetics of the alkaline hydrolysis of some phenyl esters of phosphorus acids. An estimate was made of the contribution made by the induction effect and the pp-dp conjugation of the phenoxyl group to the free activation energy of the alkaline hydrolysis of the investigated esters.

The kinetics of the hydrolysis of bis (chloromethyl)phosphinic esters was investigated in KOH medium at 10 and 25°. The rate constants are correlated with the steric constants of the leaving groups.

A study was made of the hydrolysis kinetics of some esters of bis(chloromethyl)phosphinic acid in water at 75–95°. The reaction rate depends on the nature of the alcohol radical, and for the alkyl radicals is determined by the steric factor.

1.The rate constants for the hydrolysis of tetraethyl dithiopyrophosphate in aqueous dioxane solutions of various compositions at 80°C and their temperature dependence in 50% dioxane solution have been determined.2.The constancy of the ratio of the hydrolysis rate constants of tetraethyl dithiopyrophosphate and tetraethyl monothiopyrophosphate with a change in the composition of the mixed solvents has been established, which indicates the mechanisms of the solvation of these compounds are similar.