Relationship between immune regulation and structure of polysaccharides / 中国中药杂志

Polysaccharides have significant immunomodulatory activity and have good development value in food and medicine fields. At present, there are many studies on the chemical structure and immune activity of polysaccharides, but the relationship between them of polysaccharides has not been fully explained, which limits the further development and utilization of polysaccharide resources. The immune activity of polysaccharides is closely related to their own structure. This paper systematically summarized the relationship between the relative molecular weight, monosaccharide composition, glycosidic bond types, chemical modification, and advanced conformation of polysaccharides and the immune regulation, aiming to provide references for the profound study of polysaccharide structure-activity relationship and utilization of polysaccharides.

In vitro stability of various enzymes by proline from H2O2 mediated oxidative damage

Plants under stress need to favour certain pathways so as to survive the stress period. Protection of specific enzymes by proline and other osmolytes could be one such mechanism to favour some pathways/processes. Therefore, the influence of osmolyte proline on conformational changes of various proteins caused by hydrogen peroxide (H2O2) was studied by intrinsic and extrinsic fluorescence emissions. H2O2 caused conformational change in proteins. Results indicated that for Alcohol dehydrogenase (AD) and Glutamate dehydrogenase (GD) enzymes, H2O2 induced conformational change was high and that for Glucose 6-phosphate dehydrogenase (G6PDH) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was low. Fluorescence and far-UV, CD measurements of catalase demonstrated that the H2O2 stabilized the protein secondary structure at low concentrations but destabilized it at higher concentrations. Intrinsic and ANS fluorescence results showed that proline at a concentration of 1.0 M prompted a reduction in the H2O2-induced exposed hydrophobic surfaces of studied enzymes, to different degrees which suggests its differential protective effect. Furthermore, SDS-PAGE studies revealed that proline was not able to reduce or inhibit the H2O2 mediated aggregation of GAPDH.

Effects of tetrandrine derivative HL-49 on biological property of Bloom DNA helicase / 中国药理学通报

Aim To study the effect of tetrandrine derivative HL-49 on the conformation and biological ac-tivity of Bloom helicase ( BLM ) , and to explore its antitumor mechanism.Methods The effect of HL-49 on the conformation of BLM helicase was studied by ultra- violet spectroscopy.The effects of HL-49 on DNA binding activity, DNA chain dissociation activity and ATPase activity of HL-49 on BLM DNA helicase were analyzed by fluorescence polarization and malachite green-ammonium phosphomolybdate colorimetric method.Results HL-49, a tetrandrine derivative, indirectly inhibited the ATPase activity of BLM DNA heli- case and DNA unwinding activity by reversible binding with DNA.The results of fluorescence polarization experiments showed that HL-49 could not affect the bind ing activity of BLM DNA helicase to DNA (dsDNA/ss- DNA) , but could bind to DNA in a concentration-de- pendent manner (P < 0.01).With the increase of HL- 49 concentration, the DNA unwinding ability of BLM DNA helicase decreased, and the Kobs value decreased gradually.The results of malachite green-ammonium phosphomolybdate colorimetry showed that HL-49 could significantly inhibit the ATPase activity of BLM DNA helicase.Conclusions HL49 can inhibit the ATPase activity and DNA unwinding activity of BLM DNA helicase by the reversible binding with DNA.

Rearrangement of T cell receptor genes Tcra and Tcrd and its regulatory mechanism / 中华微生物学和免疫学杂志

The high diversity of T cell receptors (TCRs) is the basis for recognizing antigens, playing an essential role in adaptive immunity. TCR diversity is generated from V(D)J rearrangement during the thymocyte development in the thymus. Standing out from the four TCR genes, Tcra and Tcrd genes are characterized by locating at the same locus and sharing specific V genes. Hence, their rearrangement and regulation have a certain particularity. Previous studies mainly focused on cis-regulatory elements and trans-acting factors regulating the Tcra/ Tcrd rearrangement. However, recent progress has shown that chromatin spatial organization plays an essential role in antigen receptor gene rearrangement. Chromatin organization proteins, such as CTCF-Cohesin, are involved in regulating rearrangement and enhancing the diversity of TCR repertoire by loop extrusion. Recombinase RAG also scans chromatin of antigen receptor genes for rearrangement. This review described the progress in the rearrangement of Tcra and Tcrd genes and the possible regulatory mechanism, especially the influence of the chromatin spatial organization.

Estrategia de cruzamientos para el mejoramiento de pollos Camperos. Un proyecto colaborativo INTA-universidad / Crossing strategy for breeding Campero chickens. An INTA-university collaborative project

RESUMEN El pollo campero es un ave destinado a sistemas productivos alternativos al industrial. Campero INTA es un cruzamiento simple entre poblaciones sintéticas generadas por INTA en Pergamino. Estas poblaciones se han mantenido cerradas y con bajo tamaño efectivo con el consiguiente efecto detrimental asociado a fenómenos de depresión endogámica. Con el objetivo de disponer de una población doble propósito con adecuados niveles productivos de carne y huevos y de rusticidad para ser utilizada en sistemas semi-intensivos que preservan el bienestar animal, se implementó un programa de relevamiento del recurso genético disponible y se diseñó un plan de cruzamientos dirigido a la producción de un híbrido terminal de tres vías. La secuencia incluyó la evaluación de cinco poblaciones sintéticas maternas (A, E, DE, ES y CE), la selección de dos de ellas (ES y A), su caracterización en cruzamientos simples recíprocos [(ESxA) y (AxES)], la elección de la alternativa (ESxA) como progenitor femenino y su cruzamiento por gallos de la estirpe paterna mejorada AH' para la obtención como producto final del pollo Campero Casilda. La evaluación de su patrón de crecimiento, conformación corporal, relación de conversión y caracteres productivos a la faena indican que tanto los machos como las hembras cumplen, como aves destinadas a la producción de carne, con las exigencias establecidas en el protocolo respectivo. La evaluación de los caracteres productivos a la madurez sexual, el patrón dinámico de aumento de peso del huevo y las curvas de postura califican a las hembras para su utilización como ponedoras.

ABSTRACT Campero chicken is a bird destined to production systems alternative to the industrial one. Campero INTA is a two-way cross between synthetic populations generated by INTA in Pergamino. These populations have remained closed and with a low effective size with the consequent detrimental effect associated with inbreeding depression. To have a dual-purpose population with adequate meat and egg production levels and rusticity to be used in semi-intensive systems that preserve animal welfare, a survey program of the available genetic resource was implemented and a crossbreeding plan to produce a terminal three-way hybrid was designed. The sequence included the evaluation of five maternal synthetic populations (A, E, DE, ES and CE), the selection of two of them (ES and A), their characterization in two-way reciprocal crosses [(ESxA) and (AxES)], the choice of the alternative (ESxA) as female parent and its crossing by roosters of the improved paternal line AH' to obtain the Campero Casilda chicken as the final product. The evaluation of their growth pattern, body conformation, conversion ratio and productive characters at slaughter indicate that both males and females satisfied the requirements as birds destined for meat production established in the respective protocol. The evaluation of productive characters at sexual maturity, dynamic pattern of egg weight gain and laying curves allowed to qualify the females as layers.

Dosimetric study on middle ear with three whole-brain radiotherapy techniques / 中国辐射卫生

Objective This study aims to compare the advantages and disadvantages of the three techniques in improving the target volume dose and protecting the auris media cavity and eustachian tube isthmus region by investigating the dosimetric differences of three whole-brain radiotherapy techniques. Methods Thirty patients with whole brain metastases were randomly selected to design fixed field intensity modulated radiotherapy (ff-IMRT) plan, volumetric arc modulated therapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) plan, and to meet a 95% PTV prescription dose (40 Gy). The dosimetric parameters and monitor units of the target volume and organ at risk (OAR) in the three groups of treatment plans were compared and analyzed. Results The Conformity Index (CI) of the ff-IMRT plan (0.93 ± 0.02) was better than the VMAT plan (0.89 ± 0.01) and the 3DCRT plan (0.73 ± 0.03), respectively, and the difference was statistically significant (P < 0.05). The Homogeneity Index (HI) of the three plans were ff-IMRT (0.05 ± 0.01)、VMAT(0.08 ± 0.1) and 3DCRT (0.08 ± 0.01), respectively, and the difference was not statistically significant (P > 0.05). The Gradient Index (GI) were ff-IMRT (1.77 ± 0.1), VMAT (1.61 ± 0.07), 3DCRT (1.39 ± 0.08), respectively. The difference was statistically significant (P < 0.05). The monitor units (MU) were ff-IMRT (1551.97 ± 85.02), VMAT (303.7 ± 24.28) and 3DCRT (226.2 ± 2.5), respectively, the difference was statistically significant (P < 0.05). The Dmax of the middle ear of the three plans were ff-IMRT (2557.54 ± 477.39) cGy, VMAT (3107.9 ± 362.28) cGy, 3DCRT (4055.37 ± 71.45) cGy, respectively. The Dmax of the eustachian tube isthmus were ff-IMRT (2425 ± 380.4) cGy, VMAT (2902.4 ± 526.3) cGy and 3DCRT (3862.7 ± 135.9) cGy, the difference were statistically significant (P < 0.05). Conclusion In whole-brain radiotherapy, ff-IMRT and VMAT significantly reduced the dose of the bilateral middle ear cavities and eustachian tube isthmus compared with 3DCRT. VMAT is recommended for WBRT for reducing the number of monitor units significantly.

3D disorganization and rearrangement of genome provide insights into pathogenesis of NAFLD by integrated Hi-C, Nanopore, and RNA sequencing

The three-dimensional (3D) conformation of chromatin is integral to the precise regulation of gene expression. The 3D genome and genomic variations in non-alcoholic fatty liver disease (NAFLD) are largely unknown, despite their key roles in cellular function and physiological processes. High-throughput chromosome conformation capture (Hi-C), Nanopore sequencing, and RNA-sequencing (RNA-seq) assays were performed on the liver of normal and NAFLD mice. A high-resolution 3D chromatin interaction map was generated to examine different 3D genome hierarchies including A/B compartments, topologically associated domains (TADs), and chromatin loops by Hi-C, and whole genome sequencing identifying structural variations (SVs) and copy number variations (CNVs) by Nanopore sequencing. We identified variations in thousands of regions across the genome with respect to 3D chromatin organization and genomic rearrangements, between normal and NAFLD mice, and revealed gene dysregulation frequently accompanied by these variations. Candidate target genes were identified in NAFLD, impacted by genetic rearrangements and spatial organization disruption. Our data provide a high-resolution 3D genome interaction resource for NAFLD investigations, revealed the relationship among genetic rearrangements, spatial organization disruption, and gene regulation, and identified candidate genes associated with these variations implicated in the pathogenesis of NAFLD. The newly findings offer insights into novel mechanisms of NAFLD pathogenesis and can provide a new conceptual framework for NAFLD therapy.

A novel DNAH5 variant in a Tunisian patient with primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous hereditary disease caused by the structural abnormalities and dysfunction of motile cilia. The DNAH5 is the most frequently mutated gene in PCD patients and hot spot exons were reported in this gene. Here, we aim to screen mutations in a set of five hot spot exons of DNAH5 gene in a cohort of 10 clinically diagnosed Tunisian PCD patients using an optimized polymerase chain reaction-single-strand conformational polymorphism screening technique. Only one patient harboured a novel heterozygous variant in exon 63 (c.10767A[G), which was inherited from his father. This variant activates a cryptic splicing site. No deleterious mutation has been identified while screening the exons of the remaining patients. Our results show that the reported hot spot exons of DNAH5 gene are not mutated in Tunisian PCD patients. This is probably due to the differences of ethnical background of the previously reported patients. Further investigations should be performed to identify the mutations underlying PCD in this group of patients.

Principal component analysis of linear measures of young horses national champions of Mangalarga Marchador breed / Análise de componentes principais das medidas lineares de equinos jovens campeões nacionais da raça Mangalarga Marchador

ABSTRACT: The conformation is directly related to the quality of the movements, and can direct the selection by equine aptitude. This study aimed to identify which are the morphometric measurements that explain the total variance available in the marcha batida and picada gaits of young Mangalarga Marchador horses. Analyses were performed by evaluating 20 linear measurements of 420 champion horses. Measures were separated by gender (male-M and female-F), type of marcha, (batida-MB e picada-MP) and divided into eight age groups. Principal component analysis (PCA) was used to identify which measurements were most important in determining marcha variance by selecting principal component (PC) which sum of eigenvalues ​​was able to explain the minimum percentage of 80% of the total variation. The PC number varied randomly according to age groups, being 2 to 3 in both genders in MP, 3 to 4 for M-MB, and up to 5 for F-MB, suggesting lower overall variability in MP, and higher in F-MB. There was no defined pattern concerning the amount of PC per age group, demonstrating that each category may have independent variations. Although, some repetitions of variables occurred similarly in different ages, sexes, and marcha types, the responsibility for the highest occurrence of variation was the posterior cannon and gaskin length. The significant variance in the length of these segments, regardless of gender, age, and marcha, and the fact they are not measured daily suggested there is not only a lack of standardization of these segments, but there is also size compensation among them since the group evaluated is composed of breed champions.

RESUMO: A conformação pode estar diretamente relacionada a qualidade dos movimentos direcionando a seleção dos equinos por aptidão. Objetivou-se identificar quais medidas lineares explicam a variância total disponível nas marchas batida e picada em cavalos jovens da raça Mangalarga Marchador. As análises foram realizadas pela avaliação de 20 medidas lineares de 420 equinos campeões de exposições, separados por sexo (macho-M e fêmeas-F), tipo de marcha (batida-MB e picada-MP) e oito grupos etários. Utilizou-se análise de componentes principais (ACP) para identificar quais características eram mais importantes na determinação da variância das marchas, selecionando aquelas contidas em CP, cuja soma de autovalores foi capaz de explicar o percentual mínimo de 80% da variação total. O número de CP variou de acordo com as faixas etárias, sendo de 2 a 3 em M e F-MP, de 3 a 4 para M-MB e até 5 para F-MB, o que sugere menor variação em animais de MP, e maior em F-MB. Não houve padrão na quantidade de CP por classe etária demonstrando variações independentes entre categorias. A maior variância geral foi explicada pelo comprimento de canela posterior e perna. A grande variância no comprimento desses segmentos, independentemente de sexo, idade, tipo de marcha e o fato dos mesmos não serem mensurados cotidianamente, sugere que não ocorre somente a ausência de padronização, mas também há compensação de tamanho entre eles, visto que se avaliou apenas animais campeões da raça.

Analysis of amino acid variations of major proteins from severe acute respiratory syndrome coronavirus 2 / 第二军医大学学报

Objective To identify key amino acid variations of major proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by biophysical methods. Methods Through amino acid sequence alignment, classification of variant amino acid residues, three-dimensional structure reconstruction of proteins, and electrostatic interaction analysis of amino acid residues, the key amino acid variations of major proteins from SARS-CoV-2 was analyzed with RaTG13, the bat coronavirus with the highest homology, as the reference. Results At least ten amino acid variations that affect the possible electrostatic interactions were identified in RNA-dependent RNA polymerase (RdRp), exoribonuclease (ExoN), uridylate-specific endoribonuclease (NendoU), and spike (S) protein from SARS-CoV-2. These variations may affect the spatial conformation and biological functions of the proteins. Conclusion The key amino acid variations of the major proteins from SARS-CoV-2 have been preliminarily identified, providing clues for understanding the genetic, pathogenic and epidemiological characteristics of the virus..

Advances in three-dimensional genomics / 生物工程学报

Three-dimensional (3D) genomics is an emerging discipline that studies the 3D spatial structure and function of genomes, focusing on the 3D spatial conformation of genome sequences in the nucleus and its biological effects on biological processes such as DNA replication, DNA recombination and gene expression regulation. The invention of chromosome conformation capture (3C) technology speeds up the research on 3D genomics and its related fields. Furthermore, the development of 3C-based technologies, such as the genome-wide chromosome conformation capture (Hi-C) and chromatin interaction analysis using paired-end tag sequencing (ChIA-PET), help scientists get insight into the 3D genomes of various species. Aims of 3D genomics are to reveal the spatial genome organization, chromosomal interaction patterns, mechanisms underlying the transcriptional regulation and formation of biological traits of microorganism, plant, animal. Additionally, the identification of key genes and signaling pathways associated with biological processes and disease via chromosome 3C technology boosts the rapid development of agricultural science, life science and medical science. This paper reviews the research progress of 3D genomics, mainly in the concept of 3D genomics, the development of chromosome 3C technologies and their applications in agricultural science, life science and medical science, specifically in the field of tumor.

Three-dimensional chromosome conformation capture and its derived technologies / 生物工程学报

Linear chromatin is compacted into eukaryotic nucleus through a complex and multi-layered architecture. Consequently, chromatin conformation in a local or long-distance manner is strongly correlated with gene expression. Chromosome conformation capture (3C) technology, together with its variants like 4C/5C/Hi-C, has been well developed to study chromatin looping and whole genome structure. In this review, we introduce new technologies including chromosome capture combined with immunoprecipitation, nuclei acid-based hybridization, single cell and genome sequencing, as well as their application.

D3Targets-2019-nCoV: a webserver for predicting drug targets and for multi-target and multi-site based virtual screening against COVID-19

A highly effective medicine is urgently required to cure coronavirus disease 2019 (COVID-19). For the purpose, we developed a molecular docking based webserver, namely D3Targets-2019-nCoV, with two functions, one is for predicting drug targets for drugs or active compounds observed from clinic or / studies, the other is for identifying lead compounds against potential drug targets docking. This server has its unique features, (1) the potential target proteins and their different conformations involving in the whole process from virus infection to replication and release were included as many as possible; (2) all the potential ligand-binding sites with volume larger than 200 Å on a protein structure were identified for docking; (3) correlation information among some conformations or binding sites was annotated; (4) it is easy to be updated, and is accessible freely to public (https://www.d3pharma.com/D3Targets-2019-nCoV/index.php). Currently, the webserver contains 42 proteins [20 severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) encoded proteins and 22 human proteins involved in virus infection, replication and release] with 69 different conformations/structures and 557 potential ligand-binding pockets in total. With 6 examples, we demonstrated that the webserver should be useful to medicinal chemists, pharmacologists and clinicians for efficiently discovering or developing effective drugs against the SARS-CoV-2 to cure COVID-19.

Effects of dihydromyricetin on biological properties of Bloom syndrome helicase / 中国药理学通报

; Aim To explore the anti-tumor mechanism of dihydromyricetin (DMY), a kind of flavonoid compound with anti-inflammatory and anti-tumor effects, via studying the effect of DMY on biological activities of Bloom helicase. Methods The effect of DMY on the biological activities of BLM helicase was studied by ultraviolet spectrum (UV), circular dichroism (CD), fluorescence polarization and free phosphorus detection. Results The results of CD and UV showed that DMY could bind to a site of the BLM helicase. In the concentration of DMY in 0 ~ 25 μmol . L 1 range, DMY showed a positive correlation with the interference ability of BLM helicase secondary structure with the increase of concentration, while in the concentration of DMY in 25 ~ 75 μmol . L 1 range, DMY showed a negative correlation. Fluorescence polarization and free phosphorus detection experiments showed that DMY could bind to BLM helicase, thus inhibiting the helicase activity of BLM helicase. Conclusions DMY can competitively bind to the DNA binding site of BLM helicase and change the spatial structure of BLM helicase, inhibiting the binding of BLM helicase to DNA and the biological activity of BLM helicase accordingly.

Nongenetic effects and genetic parameters of the limb measurements in Iranian Turkoman horses / Efeitos não genéticos e parâmetros genéticos das medidas dos membros em cavalos turcomanos iranianos

From the past to now, body conformation is an instrument for the Iranian horse judging. This research aimed to study and estimate the genetic and nongenetic parameters of limb conformation traits in the Iranian Turkoman horses. Therefore, body conformation traits, specifically limb conformation, of 1273 horses were measured. Among the horses studied, 357 stallions and 916 mares were included. For studying the nongenetic (such as sex, province and birth year) and genetic effects (such as additive genetic effect), the LSMEANS procedure and the restricted maximum likelihood method (REML) were used by SAS and MATVEC software, respectively. Birth year had a significant effect on most of the traits, especially scapula length and arm length (P < 0.05). The lowest and the highest heritability was estimated for femur length (0.11 ± 0.03) and forearm length (0.40 ± 0.09), respectively. Overall, considering the heritability estimations, the expectation is that limb conformation traits will have a good response to the selection and genetic progress. Farmers can choose the best stallions and mares based on the traits mentioned, so that their foals can have good body conformation.(AU)

Do passado para o presente, a conformação corporal é um instrumento para o julgamento de cavalos iranianos. Esta pesquisa teve como objetivo estudar e estimar os parâmetros genéticos e não genéticos das características de conformação dos membros nos equinos turcomanos iranianos. Portanto, as características de conformação do corpo, especificamente a conformação dos membros de 1273 cavalos foram medidas. Entre os cavalos estudados, 357 garanhões e 916 éguas foram incluídos. Para estudar os não genéticos (como sexo, província e ano de nascimento) e efeitos genéticos (como efeito genético aditivo), o procedimento LSMEANS e o método de máxima verossimilhança restrita (REML) foram utilizados pelo software SAS e MATVEC, respectivamente. O ano de nascimento teve um efeito significativo na maioria das características, especialmente comprimento da escápula e comprimento do braço (P < 0,05). A menor e mais alta herdabilidade foi estimada para o comprimento do fêmur (0,11 ± 0,03) e comprimento do antebraço (0,40 ± 0,09), respectivamente. No geral, considerando as estimativas de herdabilidade, a expectativa é que as características de conformação do membro tenham uma boa resposta à seleção e progresso genético. Os agricultores podem escolher os melhores garanhões e éguas com base nas características mencionadas, para que seus potros possam ter uma boa conformação corporal.(AU)

Estimation of the Degree of Salivary Acidification of Recombinant-Human-Erythropoietin(rhEPO) / 中国药学杂志

OBJECTIVE: To detect and analyze the degree of salivary acidification of rhEPO isoforms. METHODS: The isoelectric points of rhEPO isoforms were determined with full column imaging capillary isoelectric focusing electrophoresis. And the charge distribution among rhEPO isoforms was analyzed. The degrees of rhEPO's total saliva acidification were measured using the method of appendices of Chinese Pharmacopoeia. At last, the degrees of saliva acidification of rhEPO isoforms were obtained using multivariate linear fitting. RESULTS: Nine kinds of rhEPO isoforms were distinguished and defined as isoform 1 to 9 with isoelectric points in the range of 3.6 to 5.1. There was one sialic acid molecule between two contiguous rhEPO isoform. Furthermore, the degrees of salivary acidification of the main four kinds of isoforms, 4-7, were 13, 12, 11 and 10 mol/mol, respectively. CONCLUSION :This study lays foundation for rhEPO biosimilar evaluation and further analysis of each isoform of rhEPO.

Pb2+-Induced Allosteric PS2.M as A Label-Free Colorimetric Sensor for Detection of Cumulative Radon Radiation / 分析化学

A new sensitive method for detection of cumulative radon radiation based on the lead was established. PS2.M which stabilized by K+with hemin as a co-factor exhibits superior peroxidase-like activity, and can effectively catalyze the H2O2-mediated oxidation of TMB. In the presence of Pb2+, K+-stabilized PS2.M DNAzymes are induced to undergo a conformational change,because Pb2+has a higher efficiency with regard to stabilizing G-quadruplexes than K+, accompanied by a decrease of catalytic activity and a sharp decrease of readout signal. In the work, a novel"turn-off"model of colorimetry-Pb2+biosensor based on superior peroxidase-like activity of G-quadruplex for Pb2+analysis was developed. The fading degree of reaction system (△A value) was linearly related to Pb2+concentration in the range of 5. 0×10-9-1. 8× 10-7mol/L. The linear regression equation was △A=0.36+0.13C (10-8mol/L), with R=0.9987. The detection limits of lead and radon were 3.76 nmol/L(S/N=3) and 1.96×103Bq·h/m3(S/N=3), respectively. The method exhibited good selectivity, high sensitivity and convenient operation, and could avoid the radioactive hazard in determination of the radon in environment.

Investigation of Protonated and Lithiated Leucine-Enkephalin by Hydrogen/Deuterium Exchange and Theoretical Calculations / 分析化学

Differences of protonated and lithiated leucine-enkephalin(LE) were investigated by hydrogen deuterium exchange-mass spectrometry(HDX-MS) combined with quantum chemistry calculation. The results revealed that the protonated ions possessed very high product yield with all hydrogen atoms being exchanged, while the reaction of lithiated LE stopped after exchanging five hydrogen atoms in the same experimental conditions. The different HDX behaviours probably indicated their conformational differences. To further clarify the experimental results, the most stable conformations of protonated and lithiated leucine-enkephalin were calculated by density functional theory. It was found that terminal amino group was the most thermodynamically stable protonation site,while Li+in coordination of four carbonyl oxygen atoms formed the most favourable lithiated LE. The reaction field reduction of lithium LE was probably due to the less acidity of hydrogen atoms and the increasing rigid conformation change induced by lithium ion.

Progress in the applications of high-speed atomic force microscopy in cell biology / 南方医科大学学报

Without losing its high resolution, high-speed atomic force microscope (HS-AFM) represents a perfect combinationof scanning speed and precision and allows real-time and observation of the dynamic processes in a biological system atboth the cellular and molecular levels. By combining the extremely high temporal resolution with the spatial resolution andcoupling with other advanced technologies, HS-AFM shows promising prospects for applications in life sciences such as cellbiology. In this review, we summarize the latest progress of HS-AFM in the field of cell biology, and discuss the impact ofenvironmental factors on conformation dynamics of DNA, the binding processes between DNA and protein, the domainchanges of membrane proteins, motility of myosin, and surface structure changes of living cells.

Advances in small molecular drugs targeted mutant p53 / 中国药理学通报

Tumor suppressor p53 protein can regulate the tran-scription of target genes, to control cell apoptosis, aging and other life activities,but mutant p53 is prone to losing antitumor function, thus promoting tumor development. At present, p53 protein has become one of the hot targets for the treatment of cancer. This article mainly introduces the structure and mechanism of small molecular compounds with restoring activity of mutant p53 as the target.