Engineered T cells and their therapeutic applications in autoimmune diseases.

Chimeric antigen receptor T cells (CAR-T cells) are engineered recombinant T cells, which were initially used to treat hematopoietic malignancies and are now widely used in the treatment of various diseases. Considering their intrinsic targeting efficiency, CAR-T cells show considerable potential in the treatment of autoimmune diseases. Furthermore, regulatory T cells (Treg), a subset of CD4 T cells exhibiting immunosuppressive functions, have attracted increasing attention regarding CAR-Treg cell production. In this review, we report on recent developments in preclinical and clinical studies on CAR-T cells in autoimmune diseases and provide an outlook on opportunities and challenges of CAR-T application in such diseases.

[Fine root biomass of four main vegetation types in Daluo Mountain of Ningxia, Northwest China].

By the method of soil core sampling, this paper studied the fine root biomass, soil water content, and soil bulk density in 0-40 cm soil layer of four main vegetation types (Picea crassifolia forest, Pinus tabulaeformis forest, deciduous shrubs, and desert grassland) in Daluo Mountain of Ningxia, and the fine root biomass in the 0-40 cm soil layer of P. crassifolia forests with the ages of 50-, 70-, and 100 a. The fine root biomass of the four vegetation types was mainly distributed in 0-20 cm soil layer, with the rank of P. tabulaeformis forest > P. crassifolia forest > deciduous shrubs > desert grassland, and the fine root biomass of P. tabulaeformis forest was significantly higher than that of the other three vegetation types. The fine root biomass of the P. crassifolia forests with different ages was 70 a > 100 a > 50 a, and there were no significant differences in the live fine root biomass ratio and dead fine root biomass ratio among the three P. crassifolia forests. The soil water content in the 0-40 cm soil layer of the four vegetation types was P. crassifolia forest > P. tabulaeformis forest > deciduous shrubs > desert grassland, while the soil bulk density followed an opposite pattern, and was significantly negatively correlated with the fine root biomass.

A folding "framework structure" of Tetrahymena group I intron.

We have published the dynamic extended folding (DEF) method, which is a RNA secondary structure prediction approach-to simulate the in vivo RNA co-transcriptional folding process. In order to verify the reliability of the method, we selected the X-ray-determined Tetrahymena group I intron as a sample to construct the framework of its folding secondary structure. Our prediction coincides well with the secondary structure predicted by T.R. Cech and the X-ray diffraction crystal structure determined by Lehnert V. Our results show that the DEF framework structure of Tetrahymena group I intron reflects its function sites in a concise and straightforward manner, and the scope of the simulation was expanded.

Cardioviral RNA structure logo analysis: entropy, correlations, and prediction.

In recent years, there has been an increased number of sequenced RNAs leading to the development of new RNA databases. Thus, predicting RNA structure from multiple alignments is an important issue to understand its function. Since RNA secondary structures are often conserved in evolution, developing methods to identify covariate sites in an alignment can be essential for discovering structural elements. Structure Logo is a technique established on the basis of entropy and mutual information measured to analyze RNA sequences from an alignment. We proposed an efficient Structure Logo approach to analyze conservations and correlations in a set of Cardioviral RNA sequences. The entropy and mutual information content were measured to examine the conservations and correlations, respectively. The conserved secondary structure motifs were predicted on the basis of the conservation and correlation analyses. Our predictive motifs were similar to the ones observed in the viral RNA structure database, and the correlations between bases also corresponded to the secondary structure in the database.

Dynamic extended folding: modeling the RNA secondary structures during co-transcriptional folding.

For RNA secondary structure prediction, it is an important issue that how to deal with co-transcriptional folding during the RNA synthesis in the cell. On one hand, co-transcriptional folding, leads to the correct final structure of the whole RNA molecule. On the other hand, it may form the recognition sites for the progress of the transcription. Considering the hurdles in the experimental determination of RNA folding structures, we proposed a so-called "dynamic extended folding simulation" approach. We used two human pre-mRNA samples, the first functional alpha-gene HBZ and the fifth beta-gene HBB, to "display" the co-transcriptional folding images in detail. The modeling process starts from the prediction of a 30-nucleotide (nt) sequence, then in each update 30 nts was extended, say, 1-30, 1-60, 1-90, 1-120,..., 1-1651 nts (for HBB, 1-1606 nts). We selected the RNAstructure program to predict the folding secondary structures of all the segments. We defined "hairpin" as the unit of the secondary structure and analyzed the states of such unit during the sequential dynamic extended folding processes. We found that some hairpins are "conserved", i.e., after its appearance, it always is there in the followed foldings. Some hairpins present partially in the folding segments, and some hairpins appear for only once or twice. This phenomenon vividly depicts the generation and adjusting of the temporal structural units during the co-transcriptional folding process. It is these "hairpins" that support the thermodynamically stable structure at the end of the RNA synthesis. They may also play a role in RNA splicing process and even in the folding structure of the synthesized protein.

[Insight into relationship among mRNA coding region length, folding tendency and codon usage bias in Escherichia coli].

Escherichia coli has been regarded as a model organism in the study of codon usage bias. Most studies in this organism regarding this topic have focused their mind on translation efficiency (translation speed and translation precision) . However, some genes with low codon usage bias and high expression can not be explained by translation efficiency. And some evidence of local RNA secondary structure in coding region of Escherichia coli genes have been given. All of these need explanation from a new point of view. The genomic sequence of Escherichia coli K-12 MG 1655 was obtained from GenBank. Several parameter (Nc, CAI, GC, GC3s) of 4199 genes on codon usage bias were computed. Folding tendency of mRNA coding region was represented by its average energy of 50 nucleotides. And then, relationship among mRNA coding region length, folding tendency and codon usage bias in Escherichia coli were studied. It is argued that though translation efficiency is a primary cause that shapes the codon usage bias of highly expressed genes in Escherichia coli, mRNA coding region length and folding tendency are also unneglectable factor for codon usage bias and weakening of bias. In addition, biological significance of folding tendency in mRNA coding regions was discussed.

Detection of potential positive regulatory motifs of transcription in yeast introns by comparative analysis of oligonucleotide frequencies.

We conducted a comparative statistical analysis of tetra- through hexanucleotide frequencies in two sets of introns of yeast genes. The first set consisted of introns of genes that have transcription rates higher than 30 mRNAs/h while the second set contained introns of genes whose transcription rates were lower than or equal to 10 mRNAs/h. Some oligonucleotides whose occurrence frequencies in the first set of introns are significantly higher than those in the second set of introns were detected. The frequencies of occurrence of most of these detected oligonucleotides are also significantly higher than those in the exons flanking the introns of the first set. Interestingly some of these detected oligonucleotides are the same as well known "signature" sequences of transcriptional regulatory elements. This could imply the existence of potential positive regulatory motifs of transcription in yeast introns.

Density functional theory calculations for resveratrol.

The calculations based on the density functional theory (DFT) have been used to study the structure-activity of resveratrol in the chain reaction of autooxidation. According to the geometry obtained by using a B3LYP/6-31G**, the HOMO, LUMO of resveratrol and the spin density, the single electron distribution of the 4'- and 5-radical of resveratrol were calculated, it was found that resveratrol is a potential antioxidant. The 4'-hydroxyl group of resveratrol is more reactive than 3- and 5-positions because of the resonance effects. The dominant structure of the resveratrol radicals is a semiquinone structure which determines the stability of radicals, and the unpaired electron is mainly distributed to the O-atom and its ortho and para positions. The antioxidant activity of resveratrol is related to the spin density and the unpaired electron distribution of the O-atom.