O-glycosyltransferases from Homo sapiens contributes to the biosynthesis of Glycyrrhetic Acid 3-O-mono-β-D-glucuronide and Glycyrrhizin in Saccharomyces cerevisiae

Glycyrrhizin(GL)and Glycyrrhetic Acid 3-O-mono-β-D-glucuronide(GAMG)are the typical triterpenoid glycosides found in the root of licorice,a popular medicinal plant that exhibits diverse physiological effects and pharmacological manifestations.However,only few reports are available on the glycosylation enzymes involved in the biosynthesis of these valuable compounds with low conversion yield so far.In mammals,glycosyltransferases are involved in the phase II metabolism and may provide new solutions for us to engineer microbial strains to produce high valued compounds due to the substrate promiscuity of these glycosyltransferases.In this study,we mined the genomic databases of mammals and evaluated 22 candidate genes of O-glycosyltransferases by analyzing their catalytic potential for O-glycosylation of the native substrate,glycyrrhetinic acid(GA)for its glycodiversification.Out of 22 selected glycosyltransferases,only UGT1A1 exhibited high catalytic performance for biosynthesis of the key licorice compounds GL and GAMG.Molecular docking results proposed that the enzymatic activity of UGT1A1 was likely owing to the stable hydrogen bonding interactions and favorite conformations between the amino acid residues around substrate channels(P82~R85)and substrates.Furthermore,the complete biosynthesis pathway of GL was reconstructed in Saccharomyces cerevisiae for the first time,resulting in the production of 5.98±0.47 mg/L and 2.31±0.21 mg/L of GL and GAMG,respectively.

Population-based incremental learning for the prediction of Homo sapiens’ protein secondary structure

prediction of the protein secondary structure of Homo sapiens is one of the more important domains. Many methods have been used to feed forward neural networks or SVMs combined with a sliding window. This method’s mechanisms are too complex to be able to extract clear and straightforward physical meanings from it. This paper explores population-based incremental learning (PBIL), which is a method that combines the mechanisms of a generational genetic algorithm with simple competitive learning. The result shows that its accuracies are particularly associated with the Homo species. This new perspective reveals a number of different possibilities for the purposes of performance improvements.

A genome-wide survey of alternative translational initiation events in Homo sapiens

Alternative translational initiation is an important mechanism to increase the diversity of gene products. Although some of alternative translational initiation events have been reported, such information remains anecdotal and does not allow for any generalizations. The number of the known alternative translational initiation genes is so few that we know little about its mechanism. There is a great demand to discover more alternative translational initiation genes. However, it is arduously time-consuming to discover novel alternative translational initiation genes by the experimental method. Therefore we systematically analyzed protein sequences available in public database and predicted 1237 protein clusters as potential alternative translational initiation events. We concluded that about 8%—10% of human genes have alternative translational initiation sites. The results significantly increased the number of alternative translation initiation events and indicated that alternative translation initiation is an important and general regulation mechanism in the cellular process.

Gene polymorphisms associated with sudden decreases in heart rate during extensive peritoneal lavage with distilled water after gastrectomy

BACKGROUND Our previous study found that the telomerase-associated protein 1(TEP1,rs938886 and rs1713449)and homo sapiens RecQ like helicase 5(RECQL5,rs820196)single nucleotide polymorphisms(SNPs)were associated with changes in heart rate(HR)≥30%during peritoneal lavage with distilled water after gastrectomy.This study established a single tube method for detecting these three SNPs using two-dimensional(2D)polymerase chain reaction(PCR),and investigated whether SNP-SNP and SNP-environment interactions increase the risk of high HR variability(HRV).AIM To investigate whether genotypes,genetic patterns,SNP-SNP and SNP-environment interactions were associated with HRV.METHODS 2D PCR was used to establish a single-tube method to detect TEP1 rs938886 and rs1713449 and RECQL5 rs820196,and the results were compared with those of sanger sequencing.After adjusting for confounders such as age,sex,smoking,hypertension,and thyroid dysfunction,a nonconditional logistic regression model was used to assess the associations between the genotypes and the genetic patterns(codominant,dominant,overdominant,recessive,and additive)of the three SNPs and a risk≥15%or≥30%of a sudden drop in HR during postoperative peritoneal lavage in patients with gastric cancer.Gene-gene and geneenvironment interactions were analyzed using generalized multifactor dimensionality reduction.RESULTS The coincidence rate between the 2D PCR and sequencing was 100%.When the HRV cutoff value was 15%,the patients with the RECQL5(rs820196)TC genotype had a higher risk of high HRV than those who had the TT genotype(odds ratio=1.97;95%CI:1.05-3.70;P=0.045).Under the codominant and overdominant models,the TC genotype of RECQL5(rs820196)was associated with a higher risk of HR decrease relative to the TT and TT+CC genotypes(P=0.031 and 0.016,respectively).When the HRV cutoff value was 30%,patients carrying the GC-TC genotypes of rs938886 and rs820196 showed a higher HRV risk when compared with the GG–TT genotype carriers(P=0.01).In the three-factor model of rs938886,rs820196,and rs1713449,patients carrying the GC-TC-CT genotype had a higher risk of HRV compared with the wild-type GG-TT-CC carriers(P=0.01).For rs820196,nonsmokers with the TC genotype had a higher HRV risk compared with nonsmokers carrying the TT genotype(P=0.04).When the HRV cutoff value was 15%,patients carrying the TT-TT and the TC-CT genotypes of rs820196 and rs1713449 showed a higher HRV risk when compared with TT-CC genotype carriers(P=0.04 and 0.01,respectively).Patients carrying the GC-CT-TC genotypes of rs938886,rs1713449,and rs820196 showed a higher HRV risk compared with GG-CC-TT genotype carriers(P=0.02).When the HRV cutoff value was 15%,the best-fitting models for the interactions between the SNPs and the environment were the rs820196-smoking(P=0.022)and rs820196-hypertension(P=0.043)models.Consistent with the results of the previous grouping,for rs820196,the TC genotype nonsmokers had a higher HRV risk compared with nonsmokers carrying the TT genotype(P=0.01).CONCLUSION The polymorphism of the RECQL5 and TEP1 genes were associated with HRV during peritoneal lavage with distilled water after gastrectomy.

Cloning of Novel Tumor Metastasis-Related Genes from the Highly Metastatic Human Lung Adenocarcinoma Cell Line Anip973

A cDNA library was successfully constructed from Anip973, a human lung adenocarcinoma cell line with high metastatic potential. NIH3T3 cells were stably transfected using this cDNA library and screened for morphological changes in a soft agar assay. Genomic DNA was isolated from putative clones and the integrated sequence was retrieved by PCR and sequencing. Three known genes, ribosomal protein L23, hypothetical protein FLJ22104, and serine protease inhibitor, kazal type 6 and a number of 5＇-terminally truncated sequences were identified. Furthermore, cells transfected with ribosomal protein L23 was highly invasive compared with the empty vector as control （P 〈 0.02）. These results indicate that the expression cloning of cDNA libraries in NIH3T3 cells and subsequent screening for loss of contact inhibition in soft agar is a viable tool for identifying tumor-related genes and ribosomal protein L23 gene plays a role in cell movement and metastasis.

贵州盘县大洞发现的人类牙齿化石

对在盘县大洞发现的一枚人类上颌内侧门齿和一枚人类下颌犬齿的观察研究显示：门齿齿冠舌侧面铲形结构、齿结节、指状突及犬齿的齿带等结构具有某些与北京猿人牙齿相似的特征；

人类基因组非冗余Exon/Intron数据库的构建

以Homo.sapiensRefSeq作为原始数据库来构建EID(Exon/Intron Database)可以克服GenBank所带来的冗余问题.通过分析RefSeq基因组数据库中每个CDS(Coding Sequence,编码序列),获得构建EID的相关的数据(基因的定义、基因标识符、基因序列、蛋白质标识符、蛋白质序列、外显子和内含子的数量、大小、总数、非翻译区(UTR)内含子、内含子相位、内含子剪切位点模式).结果表明,人类24条染色体(22条常染色体和2条性染色体,共计2 870 827355 bps)中含有32 157个基因标识符(gene blocks),其中7 398个基因为假基因,4 014个基因发生了可变剪切(Al-ternative Splicing,AS),15 533个基因含有CDS内含子,765个基因含有UTR内含子,2 585个基因不含有内含子,其他的为异常基因.

Computational interaction analysis of organophosphorus pesticides with different metabolic proteins in humans

Pesticides have the potential to leave harmful effects on humans, animals, other living organisms, and the environment. Several human metabolic proteins inhibited after exposure to organophosphorus pesticides absorbed through the skin, inhalation, eyes and oral mucosa, are most important targets for this interaction study. The crystal structure of five different proteins, PDBIDs： 3LII, 3NXU, 4GTU, 2XJ1 and 1YXA in Homo sapiens （H. sapiens）, interact with organophosphorus pesticides at the molecular level. The 3-D structures were found to be of good quality and validated through PROCHECK, ERRAT and ProSA servers. The results show that the binding energy is maximum -45.21 relative units of cytochrome P450 protein with phosmet pesticide. In terms of H-bonding, methyl parathion and parathion with acetylcholinesterase protein, parathion, methylparathion and phosmet with protein kinase C show the highest interaction. We conclude that these organophosphorus pesticides are more toxic and inhibit enzymatic activity by interrupting the metabolic pathways in H. sapiens.

Comparative studies on storage cells in tardigrades during starvation and anhydrobiosis

The impact of starvation and anhydrobiosis on the number and size of the storage cells in the tardigrade species Milnesium tardigradum, Paramacrobiotus tonollii and Macrobiotus sapiens was investigated to gain more insight on the energetic side of anhydrobiosis. Storage cells are free floating cells within the body cavity of tardigrades and are presumed to store and release energy in form of glycogen, protein and fat to maintain a constant nutrient regime for the other tissues. The body size of the animals was not correlated with the size of the storage cells, however, M. tardigradum the largest species analysed also had the largest storage cells. A reduction in the size of the storage cells is apparent in all three species after seven days of starvation. A seven-day period of anhydrobiosis leads to a decrease in cell size in M. tardigradum but not in P. tonollii and M. sapiens. Although M. sapiens was raised on green algae, and M. tardigradum and P. tonollii were fed with rotifers and nematodes this difference in nourishment was not reflected in the response of the storage cells to anhydrobiosis

A de novo germline MLH1 mutation in a Lynch syndrome patient with discordant immunohistochemical and molecular biology test results

We describe a patient with a Homo sapiens mutL homolog 1 (MLH1)-associated Lynch syndrome with previous diagnoses of two distinct primary cancers:a sigmoid colon cancer at the age of 39 years, and a right colon cancer at the age of 50 years. The mutation identified in his blood and buccal cells, c.1771delG, p.Asp591Ilefs*25, appears to be a de novo event, as it was not transmitted by either of his parents. This type of de novo event is rare in MLH1 as only three cases have been reported in the literature so far. Further-more, the discordant results observed between repli-cation error phenotyping and immunohistochemistry highlight the importance of the systematic use of both pre-screening tests in the molecular diagnosis of Lynch syndrome.

U-series Dating of Ganqian Cave in Guangxi and Its Anthropological Implications

From Ganqian (Tubo) Cave a total of 17 hominid teeth attributed to late Homo sapiens has been collected along with an abundance of mammalian fossils. The fossiliferous deposits are bracketed by the capping and second flowstone layers, which yielded 230 Th/ 234 U dates of ～93 and ～220 ka, marking the minimum and maximum age of the hominid teeth respectively. Two U series methods performed on two mammalian teeth gave dates in the range of 85 and 139 ka, lending support to the stratigraphic order of the depositional sequence. The results presented in this paper point to an occurrence of modern Homo sapiens in southern China much earlier than has been thought, which is supported by the dating of nearby Liujiang and Bailiandong hominid sites. Taken together, these data suggest that China should not be considered as a backwater in recent human evolution where all the previous populations were replaced.

What Is Humanity＇s Place in Nature, from an Objective （Biocentric） Point of View？

Are humans part of nature？ Clearly humans are, or they wouldn＇t be able to interact with it. The real question is what part are they？ Most texts define an exotic species as one translocated by humans to an area where it had not previously existed. （This would seem to make humans, throughout most of their range, an exotic species, although this fact is never mentioned）. But the effect that the species has on its new surroundings has little to do with how it got there, and more to do with its being a newcomer. What is a native species？ It is basically one that has been around a long time, i.e., not a newcomer. The question is, how long？ A length of time that makes sense is the length of time that it takes for the other species in the area to evolve to adapt to the newcomer-on the order of a million years. That would make humans native only to Africa, and everywhere else a rank newcomer （exotic species）. This is not a value judgment, just biological fact, but maybe also a good indication of how we should behave： with restraint, with the manners of a guest.

应用SAPIEN 3瓣膜行经导管肺动脉瓣置换术一例

1临床资料患者女性,29岁。因“法乐四联症矫治术后17年,活动后胸闷、气短1年”于2020年12月4日入住我院。患者曾于1993年在我院行法乐四联症外科矫治术。经胸超声心动图示:肺动脉重度狭窄[峰值压差77.4 mmHg(1 mmHg=0.133 kPa)],三尖瓣中量反流,右心室重度扩大。

Fluid-Structure Interaction in Problems of Patient Specific Transcatheter Aortic Valve Implantation with and Without Paravalvular Leakage Complication

Paravalvular Leakage(PVL)has been recognized as one of the most dangerous complications in relation to Transcathether Aortic Valve Implantation(TAVI)activities.However,data available in the literature about Fluid Structure Interaction(FSI)for this specific problem are relatively limited.In the present study,the fluid and structure responses of the hemodynamics along the patient aorta model and the aortic wall deformation are studied with the aid of numerical simulation taking into account PVL and 100%TAVI valve opening.In particular,the aorta without valve(AWoV)is assumed as the normal condition,whereas an aorta with TAVI 26 mm for 100%Geometrical Orifice Area(GOA)is considered as the patient aorta with PVL complication.A 3D patient-specific aorta model is elaborated using the MIMICS software.Implantation of the identical TAVI valve of Edward SAPIEN XT 26(Edwards Lifes ciences,Irvine,California)is considered.An undersized 26 mm TAVI valve with 100%valve opening is selected to mimic the presence of PVL at the aortic annulus.The present research indicates that the existence of PVL can increase the blood velocity,pressure drop and WSS in comparison to normal conditions,thereby paving the way to the development of recirculation flow,thrombus formation,aorta wall collapse,aortic rupture and damage of endothelium.

Early mortality and safety after transcatheter aortic valve replacement using the SAPIEN 3 in nonagenarians

Background Transcatheter aortic valve replacement （TAVR） has been performed for many elderly patients with severe aortic stenosis （AS）. The SAPIEN 3 is one of the latest balloon-expandable prosthesis. This study aimed to investigate the early clinical outcomes after TAVR using the SAPIEN 3 in nonagenarians. Methods A total of 97 consecutive patients underwent TAVR for severe AS between De- cember 2015 and December 2016. Of these, 85 consecutive patients who underwent TAVR using the SAPIEN 3 were included. According to the age, patients were classified into age 〉 90 years group （17 patients） or age 〈 90 years group （68 patients）. The clinical outcomes in- cluding all-cause mortality and composite endpoint of early safety at 30 days were evaluated. Results The Society of Thoracic Surgeons score in age 〉 90 years group was higher than age 〈 90 years group （12.3 ±6.1% vs. 8.5 ± 5.1%, P 〈 0.01）. There was no significant difference in 30-day mortality between the two groups. However, the life-threatening bleeding and major vascular complications in age 〉 90 years group were greater than age 〈 90 years group （11.8% vs. 1.5%, P = 0.04 and 11.8% vs. 1.5%, P = 0.04, respectively）. The composite endpoint of early safety at 30 days was similar between the two groups. Multivariate logistic regression analysis showed that prior myocardial infarction was an independent predictor of the composite endpoint of early safety （odds ratio： 4.76, 95% confidence interval： 1.02-22.21, P = 0.047）. Conclusions The early mortality and safety after TAVR using the SAPIEN 3 in nonagenarians were similar and acceptable despite of higher operative risk.

Evolution of computers and simulations: from science and technology to the foundations of society

We consider the relevance of computer hardware and simulations not only to science and technology but also to social life. Evolutionary processes are part of all we know, from the physical and inanimate world to the simplest or most complex biological system. Evolution is manifested by land mark discoveries which deeply affect our social life. Demographic pressure, demand for improved living standards and devastation of the natural environment pose new and complex challenges. We believe that the implementation of new computational models based on the latest scientific methodology can provide a reasonable chance of overcoming today's social problems. To ensure this goal, however, we need a change of mindset, placing findings obtained from modern science above traditional concepts and beliefs. In particular, the type of modeling used with success in computational sciences must be extended to allow simulations of novel models for social life.

运用Sapien 3瓣膜经导管股-房间隔途径二尖瓣瓣中瓣置换1例

本文报道1例因二尖瓣生物瓣衰败导致心力衰竭的患者,急需行瓣膜置换术。多学科团队决定使用Sapien 3瓣膜经股静脉-房间隔途径行经导管二尖瓣瓣中瓣植入术。术后患者恢复良好,随访发现患者心功能明显改善,超声心动图提示Sapien 3瓣膜工作正常。