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Biomedical subjects

Qun Liu

Publications and source records attributed to Qun Liu.

18 recordsLinked to original sources

Spatially resolved single-cell atlas reveals the macroevolutionary trajectory of animal hearts.

Animal hearts display diverse anatomical structures during adaptive evolution. Here, we present a multiomics atlas of adult hearts from 27 species across chordates, arthropods, and mollusks. Joint analysis indicates that Bilateria hearts share a core gene repertoire, taking a stepwise "add-on" approach as a universal evolutionary strategy. The "proto-heart" is populated by key cell types, including cardiomyocytes, fibroblasts, endothelial cells, and neural cells, which maintained core signatures while evolving with shifts in living environments and corresponding adaptations in the cardiovascular system. Additionally, we reveal an evolutionarily conserved cardiomyocyte state dynamic potentially linked to cardiac development and stress responses. Finally, we identify a common molecular program underpinning chamber evolution from a ventricular foundation. This work establishes a resource for understanding the intrinsic mechanisms of heart evolution.

Animals↗

Genomic Insights Into Local Adaptation Across Heterogeneous Understory Habitats and Climate Change Vulnerability.

Understanding adaptive evolution and survival risks in understory herbs is crucial for the effective conservation of biodiversity. How environmental gradients shape species local adaptation patterns is not well understood, nor is how populations of understory herbs respond to a changing climate. In this study, we conducted population genomic analyses of Adenocaulon himalaicum (Asteraceae) with a pan-East Asian distribution, representing a good model for dominant understory herbs to elucidate adaptation mechanisms in heterogeneous forest ecosystems. Based on 34,398 putatively neutral single nucleotide polymorphisms (SNPs) across 27 populations, we identified three genetic lineages accompanied by high levels of genetic differentiation between populations. Our isolation by environment results (IBE) indicated a significant effect of environmental gradients on genomic variation of A. himalaicum (r = 0.18, p = 0.03). To decompose the relative contributions of climate, geography and population structure in explaining genetic variance, our partial RDA found that the prominent contribution of environmental effects (climatic and soil variables) explained 29% and 36% of the neutral and adaptive genetic variation, respectively. Using two genotype-environment association (GEA) methods, we identified 13 SNPs as candidates for core climate-related adaptation loci, with two of these loci further validated by qRT-PCR experiments. Projections of spatiotemporal genomic vulnerability under different future climate scenarios revealed that populations in the southeastern edge of the Himalayas, near the Sichuan Basin, the southernmost region of Northeast China and the northern Korean Peninsula, as well as northern Japan, were identified as the most vulnerable and should be prioritised for conservation. Therefore, our current study provides the genomic foundations for conservation and management strategies to elucidate how these understory herbs cope with future climate changes.

Climate Change↗

Genome sequencing and population genomics provide insights into the demographic history, genetic load, and local adaptation of an endangered Tertiary relict.

Endangered Tertiary relict trees represent an exceptional evolutionary heritage with small and isolated populations, yet little is known about how demographic history, local adaptation, and genetic load have affected their long-term survival and extinction risk. We performed whole-genome sequencing and population genomic analyses on Ulmus elongata L. K. Fu & C. S. Ding, an endangered Tertiary relict tree endemic to East Asia. By integrating genomes from U. elongata and seven other endangered trees from public databases, we identified rate-decelerated genes across endangered trees and genes under positive selection of U. elongata associated with tissue development, detoxification, and immune response, and signal transduction and regulation mechanisms potentially leading to endangered status. Demographic analyses revealed continuous population decline from the late Miocene to present, especially during the last glacial maximum (LGM) and last 10&#x2009;000&#x2009;years. Spearman correlation indicated a strong negative relationship between effective population size and human population density (rpopulation density&#x2009;=&#x2009;-0.90, P&#x2009;<&#x2009;0.001) as well as cropland use (rcropland use&#x2009;=&#x2009;-0.89, P&#x2009;<&#x2009;0.001). Genotype-environment association (GEA) analyses identified a set of candidate genes associated with temperature and precipitation, supporting a polygenic adaptation model in U. elongata. Overall, our findings underscore the severe population bottlenecks that have led to the fixation of strongly deleterious mutations and inbreeding, further compromising the adaptive potential and long-term viability of U. elongata. Furthermore, assessments of genomic vulnerability under future climate scenarios revealed higher genetic offsets in northern region of Fujian and Jiangxi populations, suggesting these regions require prioritized conservation efforts due to reduced adaptive capacity.

Endangered Species↗

Purification, partial characterization and crystallization of acucetin, a protein containing both disintegrin-like and cysteine-rich domains released by auto-proteolysis of a P-III-type metalloproteinase AaH-IV from Agkistrodon acutus venom.

AaH-IV, a P-III-type metalloproteinase found in Agkistrodon acutus venom, readily cleaves itself to release a stable protein named acucetin at 310 K under neutral and weakly alkaline conditions. A partial amino-acid residue sequence of acucetin indicates that the protein has a high homology to snake-venom proteins containing both disintegrin-like and cysteine-rich domains. Acucetin has been crystallized in space group R32, with hexagonal unit-cell parameters a = b = 155.98, c = 76.07 A. The V(M) value of about 2.97 A(3) Da(-1) suggests the presence of only one molecule in the asymmetric unit.

Agkistrodon↗

The first nonthiolic, odorless 1,3-propanedithiol equivalent and its application in thioacetalization.

2-[2-Chloro-1-(1-chlorovinyl)allylidene]-1,3-dithiane 1 was synthesized by the chlorination of 3-(1,3)-dithianylidenepentane-2,4-dione 2 using the Vilsmeier-Haack reagent in 99% yield. As a novel nonthiolic, odorless 1,3-propanedithiol equivalent, 1 was investigated in the thioacetalization reaction. Various types of aldehydes and ketones 3 were converted to the corresponding dithianes 4 in the presence of 1 in high yields (79-97%). Moreover, 1 exhibited obvious chemoselectivity between aldehyde and ketone in this thioacetalization reaction. A mechanism for this thioacetalization reaction is proposed.

Journal Article↗

The crystal structure of a novel, inactive, lysine 49 PLA2 from Agkistrodon acutus venom: an ultrahigh resolution, AB initio structure determination.

The crystal structure of acutohaemolysin, a lysine 49 phospholipase A2 protein with 1010 non-hydrogen protein atoms and 232 water molecules, has been determined ab initio using the program SnB at an ultrahigh resolution of 0.8 A. The lack of catalytic activity appears to be related to the presence of Phe102, which prevents the access of substrate to the active site. The substitution of tryptophan for leucine at residue 10 interferes with dimer formation and may be responsible for the additional loss of hemolytic activity. The ultrahigh resolution of the experimental diffraction data permits alternative conformations to be modeled for disordered residues, many hydrogen atoms to be located, the protonation of the Nepsilon2 atom in the catalytic residue His48 to be observed experimentally, and the density of the bonding electrons to be analyzed in detail.

Agkistrodon↗

Synthesis and biological evaluation of hydroxamate-Based inhibitors of glutamate carboxypeptidase II.

A series of hydroxamic acids has been prepared as potential inhibitors of glutamate carboxypeptidase II (GCP II). Compounds based on a P1' residue (primed-side inhibitors) were more potent than those based on a P1 group (unprimed-side inhibitors). Inhibitory potency of the primed-side GCP II inhibitors was found to be dependent on the number of methylene units between the hydroxamate group and pentanedioic acid. Succinyl hydroxamic acid derivative, 2-(hydroxycarbamoylmethyl)pentanedioic acid, is the most potent GCP II inhibitor with an IC(50) value of 220nM. The comparison of the results to those of other classes of GCP II inhibitors as well as hydroxamate-based MMP inhibitors provides further insight into the structure-activity relationships of GCP II inhibition.

Aeromonas↗

Low-resolution molecular replacement using a six-dimensional search.

A parallel-aware program MPI_FSEARCH has been implemented to perform molecular replacement using an exhaustive six-dimensional search. In particular, the program can be used to deal with diffraction data at very low resolution (d > 10 A) that would normally not be appropriate for other molecular-replacement programs such as AMoRe and CNS. Although an envelope constructed from a PDB (Protein Data Bank) file was tested in the present study, the program can be used to perform low-resolution molecular replacement with an envelope derived from various sources such as electron microscopy or small-angle solution X-ray scattering.

6-Phytase↗

Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.

A series of 2-(thioalkyl)pentanedioic acids were synthesized and evaluated as inhibitors of glutamate carboxypeptidase II (GCP II, EC 3.4.17.21). The inhibitory potency of these thiol-based compounds against GCP II was found to be dependent on the number of methylene units between the thiol group and pentanedioic acid. A comparison of the SAR of the thiol-based inhibitors to that of the phosphonate-based inhibitors provides insight into the role of each of the two zinc-binding groups in GCP II inhibition. The most potent thiol-based inhibitor, 2-(3-mercaptopropyl)pentanedioic acid (IC(50) = 90 nM), was found to be orally bioavailable in rats and exhibited efficacy in an animal model of neuropathic pain following oral administration.

Administration, Oral↗

Arsenic trioxide-induced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL.

Arsenic trioxide (ATO) has been shown to induce differentiation and apoptosis in acute promyelocytic leukemia (APL) cells concomitant with down-regulation of the PML-RARalpha fusion protein, a product of the t(15:17) translocation characteristic of APL leukemic cells. However, ATO is also a potent inducer of apoptosis in a number of other cancer cells lacking the t(15:17) translocation. The exact mechanism of ATO-induced apoptosis in these cells is not yet clear. We tested the effect of ATO on 7 myeloma cell lines with varying p53 status and report that in cells with mutated p53, ATO induced rapid and extensive (more than 90%) apoptosis in a time- and dose-dependent manner concomitant with arrest of cells in G(2)/M phase of the cell cycle. Myeloma cells with wild-type (wt) p53 were relatively resistant to ATO with maximal apoptosis of about 40% concomitant with partial arrest of cells in G(1) and up-regulation of p21. The use of caspase blocking peptides, fluorescence-tagged caspase-specific substrate peptides, and Western immunoblotting confirmed the involvement of primarily caspase-8 and -3 in ATO-induced apoptosis in myeloma cells with mutated p53 and primarily caspase-9 and -3 in cells expressing wt p53. We also observed up-regulation by ATO of R1 and R2 APO2/TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) receptors. Most important, however, we observed a synergy between ATO and APO2/TRAIL in the induction of apoptosis in the partially resistant myeloma cell lines and in myeloma cells freshly isolated from myeloma patients. Our results justify the use of the combination of these 2 drugs in clinical setting in myeloma patients.

Apoptosis↗

Potentiation of dexamethasone-, paclitaxel-, and Ad-p53-induced apoptosis by Bcl-2 antisense oligodeoxynucleotides in drug-resistant multiple myeloma cells.

Overexpression of Bcl-2 in myeloma cells results in resistance to drugs such as dexamethasone (DEX), adenovirus-mediated delivery of p53 (Ad-p53), and paclitaxel (TAX), which work through the intrinsic apoptotic pathway. Bcl-2 antisense oligodeoxynucleotides (Bcl-2-ASO) have been shown to induce apoptosis in cancer cells, as a single agent or, better, in combination with chemotherapy. We hypothesized that down-regulation of Bcl-2 by Bcl-2-ASO will sensitize drug-resistant myeloma cells to undergo apoptosis. In this paper we report a detailed time/dose study of the effect of Bcl-2-ASO on myeloma cells with varying levels of Bcl-2. Treatment of myeloma cells expressing relatively low levels of Bcl-2 with Bcl-2-ASO resulted in a substantial apoptosis concomitant with a substantial depletion of Bcl-2 protein. Maximal apoptosis was observed at 5 to 10 microg/mL Bcl-2-ASO, following 4 days of treatment. Down-regulation of Bcl-2 and apoptosis were time and dose dependent and were sequence specific. In these cell lines, apoptosis was accompanied by activation of caspase-9 and caspase-3 and by release of cytochrome c to the cytosol. In contrast, high Bcl-2-expressing myeloma cells were practically resistant to Bcl-2-ASO. Most important, however, pretreatment of myeloma cells expressing high levels of Bcl-2 with Bcl-2-ASO increased the extent of DEX-, TAX-, and Ad-p53-induced apoptosis from 10%-20% to 70%-90%. Increased apoptosis was accompanied by additional decrease in Bcl-2 protein. Similar results for down-regulation of Bcl-2 and apoptosis were obtained with freshly isolated myeloma cells. These data support development of clinical trials with combinations of Bcl-2-ASO and DEX, TAX, or Ad-p53 in the treatment of refractory myeloma patients.

Apoptosis↗

Detection of embryo sex chromosome by dual color fluorescent in-situ hybridization.

In order to evaluate the effects of sex chromosomal mosaicism on the accuracy of single-cell gender diagnosis, sex chromosomes of 21 normal fertilized embryos were detected by dual color fluorescent in-situ hybridization (FISH). The results showed that 4 embryos had sex chromosomal mosaicism (19%) and the remaining 17 showed uniformly XX or XY signals in all blastomeres. In conclusion, identification of sex by dual color FISH analysis of a single cell was accurate and efficient, and sex chromosomal mosaicism would not affect preimplantation gender diagnosis.

Blastocyst↗

A nitrogen budget of the Changjiang river catchment.

Based on 1997-1998 field investigations in the Changjiang river mouth, rain sampling from the river's upper reaches to the mouth, historical data, and relevant literature, the various sources of Total Nitrogen (TN) and Dissolved Inorganic Nitrogen (DIN) in the Changjiang river catchment and N transport in the Changjiang river mouth were estimated. The export fluxes of various form of N were mainly controlled by the river runoff, and the export fluxes of NO3-N, DIN and TN in 1998 (an especially heavy flood year) were 1438 10(3) tonnes (t) yr(-1) or 795.1 kg km(-2) yr(-1), 1746 10(3) t yr(-1) or 965.4 kg km(-2) yr(-1) and 2849 10(3) t yr(-1) or 1575.3 kg km(-2) yr(-1), respectively. The TN and DIN in the Changjiang river came mainly from precipitation, agricultural nonpoint sources, N lost from fertilizer and soil, and point sources of industrial waste and residential sewage discharge, which were about 56.2% and 62.3%, 15.4% and 18.5%, 17.1% and 14.4%, respectively, of the N outflow at the Changjiang river mouth; maximum transport being in the middle reaches.

China↗

[Selectivity and tolerance of sea urchin (Hemicentrotus pulcherrimus) to environmental change].

An experimental ecological study of sea urchin (Hemicentrotus pulcherrimus) sampled from coastal waters of Qingdao was focused on the fundamental ecological factors such as temperature, salinity, light intensity and substratum. The results showed that the suitable ecological range of temperature was from 8 degrees C to 22 degrees C, and the selectivity to temperature was changed with the previous living temperatures. Hemicentrotus pulcherrimus was a kind of stenohaline creature. Its optimum ecological range of salinity was from 30 to 35. The results also showed that Hemicentrotus pulcherrimus liked to select weak light environment (< 50 lux), especially under non-food condition. Hemicentrotus pulcherrimus had the positive substratum-selectivity to coarse sand and the negative substratum-selectivity to silver sand.

Animals↗

Clinical and experimental pathology of Moyamoya disease.

OBJECTIVE: To investigate the etiology, pathology, and mechanism of pathogenesis of Moyamoya disease. METHODS: A total of 15 human autopsies were analyzed. In addition, in order to create an animal model of the disease, 21 Japanese rabbits were divided randomly into two groups and subjected to injections of horse serum either intravenously or locally in the area of the sympathetic ganglia. Pathological and immunohistochemical characteristics were observed. RESULTS: The pathological features of the autopsies and the animal models both involved intima hyperplasia and stenosis or even occlusion of the lumen in the terminal ends of the internal carotid artery and the anterior and middle cerebral arteries. Disconnections or even breakages of the inner layer of the lumen were also observed, without an obvious inflammatory response. Hyperplasic smooth muscle cells of the medial membrane had extended inward through broken portions of the internal elastic lamina, with intima cell hyperplasia resulting in lumen stenosis. The hyperplastic vascular walls were positive for IgG and IgM. CONCLUSIONS: The etiology of Moyamoya disease may involve allergic angiitis. A possible mechanism is that proximal portions of the circle of Willis first develop chronic stenosis or occlusion, leading to compensatory small vessel proliferation, which perforates into the cerebral parenchyma.

Adolescent↗

[Effects of cleavage-stage biopsy on in vitro development of human embryos].

OBJECTIVE: To evaluate the effects of biopsy methods, biopsy timing and the number of cell removed on in vitro development of embryos. METHODS: One hundred and fifty four embryos of good morphology from in vitro fertilization patients were studied. Sixty-six embryos were allocated to the following three groups: chemical drilling biopsy group (26), mechanical drilling biopsy group (26) and control group (20). One cell was removed from the embryos of the two biopsy groups. The remaining 88 embryos were allocated to two groups: biopsy group (44) and control group (44). Two cells were removed from biopsy group by chemical drilling method. The stage of the embryo before biopsy, biopsy time, lysed blastomere, growth potential and hatching capacity of the biopsied embryos, total cell number at the blastocyst stage were recorded and evaluated. RESULTS: The mean time of biopsy in the chemical drilling group (231 +/- 20) seconds was significantly shorter than that in the mechanical drilling group (262 +/- 23) seconds (P < 0.01). The proportion of embryo developing to blastocyst stage was higher in chemical drilling group as compared with the mechanical group (65% versus 35%, P < 0.05). The total cell number at the blastocyst stage was fewer than those in the 7 to 8-cell embryo and >/= 9-cell embryo groups in the 6-cell embryo group (44 +/- 4 versus 49 +/- 5, 50 +/- 6; P < 0.05). At 9- to 10-cell stage, the proportion developing to the blastocyst stage was reduced in compacted embryos (20%) compared with control group (67%, P < 0.05) also more lysed blastomeres after biopsy were found in compacted embryos (50%) compared with uncompacted embryos (17%). The growth capacity to the blastocyst stage and the total cell number of the blastocyst were not different between one cell removal group and two cells removal group (P > 0.05). However, the proportion developing to the blastocyst stage was reduced after the removal of two cells from the 6-cell stage in comparison to the control (1/8 versus 5/8, P < 0.05). CONCLUSIONS: Compared with mechanical drilling biopsy, chemical drilling technique takes shorter timer and is safer. The suitable biopsy timing was >/= 7-cell stage before embryo compacting. The removal of two cells from >/= 7-cell would not impair in vitro development of embryos.

Adult↗

[Determination of selenium in Kaoliang seed-skin by extraction FAAS].

This paper reports the determination of selenium by FAAS, extracted with APDC and MIBK, Being extracted and enriched, it not only overcomes the shortcomings, being difficult to determine selenium for the low efficiency of atomization, but also eliminates the disturbance in determination of selenium from the stabilizer Cu2+ and the other metal ions in the sample. The method was applied to the determination of selenium in the husk of Kaoliang and had a good effect. The method is simple and rapid with good precision and accuracy. The relative standard deviation is 4.18%. The recovery is 97.8%.

Edible Grain↗