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Biomedical subjects

Lei Liu

Publications and source records attributed to Lei Liu.

At least 19 recordsLinked to original sources
PubMed2026

Metagenomic analysis of the midgut microbiome in Dermacentor abaensis ticks at different feeding states.

Ticks are blood-sucking ectoparasites of humans and animals, ranking second only to mosquitoes as vectors of diseases. Dermacentor abaensis is distributed in Sichuan, Qinghai, and Gansu, China. Because D. abaensis harbors several pathogens, it poses a threat to public health and livestock production. However, the midgut microbiota of D. abaensis at distinct feeding states remains poorly characterized. Adult D. abaensis ticks at various feeding states were collected from yaks in Gansu Province, China. Genomic DNA was extracted from midguts and midgut contents of unfed, partially fed, and fully engorged female D. abaensis. A metagenomic sequencing approach was employed to profile the midgut microflora among three groups. A total of 83 phyla, 908 genera, and 1857 species were annotated across the three groups. At the phylum level, Pseudomonadota, Mucoromycota, and Ascomycota were the most abundant. At the species level, common bacterial species such as Klebsiella pneumoniae and Anaplasma phagocytophilum, alongside viruses and eukaryotes, were detected in all three groups. Unique microorganisms were also observed in each group: unfed (n = 305), partially fed (n = 59), and fully engorged (n = 20). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that the D. abaensis microbiome contains a relatively high abundance of functional genes involved in lipid and amino acid metabolism across the three different feeding states. These findings indicate that while core microbial taxa are shared in the midgut of female D. abaensis, observable trends suggest variations in microbial diversity and composition as blood-feeding progresses. The present study provides a descriptive baseline of the midgut microbial composition of D. abaensis, which may inform future studies on tick biology and the ecology of tick-borne pathogens.

Animals↗
PubMed2025

Cr3a, a candidate gene conferring fruit cracking resistance, was fine-mapped in an introgression line of Solanum lycopersicum L.

In the cultivation and production of tomato (Solanum lycopersicum L.), fruit cracking is a prevalent and detrimental issue that significantly impacts the esthetic quality and commercial value of the fruit. The complexity of the trait has resulted in a slow advancement in research aimed at identifying genes that influence tomato fruit cracking and the underlying regulatory mechanisms. In this study, a sub-introgression population for tomato crack-resistant fruit has been constructed from the cross between S. lycopersicum 1052 and Solanum pennellii LA0716, followed by 11 generations of selfing. Utilizing specifically designed InDel markers, the tomato crack-resistant gene, Cr3a, was fine-mapped, cloned, and its functionality was confirmed through transgenic and gene-knockout approaches. The precise localization of Cr3a was delineated to a 30 kb genomic region on chromosome 3, corresponding to the gene Sopen03g034650 in S. pennellii and Solyc03g115660.3 in the Heinz1706 variety. An integrated transcriptomic and metabolomic analysis of fruits with and without the Cr3a gene was finally conducted to elucidate the intricate regulatory mechanisms associated with Cr3a. The findings revealed a molecular regulatory network for tomato fruit crack resistance, characterized by 7 key metabolites, 13 pivotal genes, and 4 critical pathways: the phenylpropanoid biosynthesis pathway, the phenylalanine, tyrosine, and tryptophan biosynthesis pathway, the linolenic acid metabolism pathway, and the cysteine and methionine metabolism pathway. In summary, this research provides novel insights into the molecular underpinnings of tomato fruit crack resistance and holds substantial promise for accelerating the molecular breeding of tomatoes with enhanced fruit crack resistance.

Solanum lycopersicum↗
PubMed2007

A shared random effects model for censored medical costs and mortality.

In this paper, we propose a model for medical costs recorded at regular time intervals, e.g. every month, as repeated measures in the presence of a terminating event, such as death. Prior models have related monthly medical costs to time since entry, with extra costs at the final observations at the time of death. Our joint model for monthly medical costs and survival time incorporates two important new features. First, medical cost and survival may be correlated because more 'frail' patients tend to accumulate medical costs faster and die earlier. A joint random effects model is proposed to account for the correlation between medical costs and survival by a shared random effect. Second, monthly medical costs usually increase during the time period prior to death because of the intensive care for dying patients. We present a method for estimating the pattern of cost prior to death, which is applicable if the pattern can be characterized as an additive effect that is limited to a fixed time interval, say b units of time before death. This 'turn back time' method for censored observations censors cost data b units of time before the actual censoring time, while keeping the actual censoring time for the survival data. Time-dependent covariates can be included. Maximum likelihood estimation and inference are carried out through a Monte Carlo EM algorithm with a Metropolis-Hastings sampler in the E-step. An analysis of monthly outpatient EPO medical cost data for dialysis patients is presented to illustrate the proposed methods.

Algorithms↗
PubMed2006

Effects of topiramate on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition in recently abstinent methamphetamine-dependent individuals.

Methamphetamine-dependent individuals often cite the need to maintain enhanced cognitive performance and attention as a reason for continuing or relapsing to drug-taking. Further, methamphetamine addicts might not comply with taking a potentially therapeutic medication if it had a profound effect on these cognitive processes. Topiramate, a sulfamate-substituted fructopyranose derivative, has been suggested as a putative therapeutic medication for treating methamphetamine dependence. Examination of topiramate's effects on cognitive performance and attention is a clinically and scientifically important component of understanding its potential therapeutic profile. In 10 male and female individuals who met DSM-IV criteria for methamphetamine dependence, we examined the effects of low (50 mg b.i.d.)- and high (100 mg b.i.d.)-dose topiramate - in both the presence and absence of low (15 mg)- and high (30 mg)-dose intravenous methamphetamine--on cognitive performance, attention, and concentration on the rapid visual information processing task and the digit symbol substitution test. Intravenous methamphetamine enhanced cognitive performance, attention, and concentration among recently withdrawn methamphetamine addicts--an effect that hitherto had not been well characterized. Topiramate's cognitive effects were mixed and rather paradoxical, with a tendency to improve attention and concentration both alone and in the presence of methamphetamine while worsening psychomotor retardation. No deleterious interaction occurred between topiramate and methamphetamine on any of these cognitive processes. While clinical studies with topiramate should prepare participants for possible psychomotor retardation, the cognitive effects profile observed would not likely present an important obstacle to compliance in motivated patients. Topiramate's complicated cognitive effects among methamphetamine addicts need more comprehensive examination.

Adult↗
PubMed2006

Spectral response variation of a negative-electron-affinity photocathode in the preparation process.

In order to research the spectral response variation of a negative electron affinity (NEA) photocathode in the preparation process, we have done two experiments on a transmission-type GaAs photocathode. First, an automatic spectral response recording system is described, which is used to take spectral response curves during the activation procedure of the photocathode. By this system, the spectral response curves of a GaAs:Cs-O photocathode measured in situ are presented. Then, after the cathode is sealed with a microchannel plate and a fluorescence screen into the image tube, we measure the spectral response of the tube by another measurement instrument. By way of comparing and analyzing these curves, we can find the typical variation in spectral-responses. The reasons for the variation are discussed. Based on these curves, spectral matching factors of a GaAs cathode for green vegetation and rough concrete are calculated. The visual ranges of night-vision goggles under specific circumstances are estimated. The results show that the spectral response of the NEA photocathode degraded in the sealing process, especially at long wavelengths. The variation has also influenced the whole performance of the intensifier tube.

Journal Article↗
PubMed2006

Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells.

Curcumin (diferuloylmethane), a polyphenol natural product of the plant Curcuma longa, is undergoing early clinical trials as a novel anticancer agent. However, the anticancer mechanism of curcumin remains to be elucidated. Here we show that curcumin inhibited growth of rhabdomyosarcoma cells (Rh1 and Rh30) (IC50 = 2-5 microM) and arrested cells in G1 phase of the cell cycle. Curcumin also induced apoptosis and inhibited the basal or type I insulin-like growth factor-induced motility of the cells. At physiological concentrations (2.5 microM), curcumin rapidly inhibited phosphorylation of the mammalian target of rapamycin (mTOR) and its downstream effector molecules, p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), in a panel of cell lines (Rh1, Rh30, DU145, MCF-7 and Hela). Curcumin also inhibited phosphorylation of Akt in the cells, but only at high concentrations (>40 microM). The data suggest that curcumin may execute its anticancer activity primarily by blocking mTOR-mediated signaling pathways in the tumor cells.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Synthesis, structure and biological activity of cobalt(II) and copper(II) complexes of valine-derived schiff bases.

We have synthesized two cobalt(II) 2 and copper(II) 3 complexes of valine-derived Schiff bases. The obtained complexes were characterized by elemental analysis, FT-IR and X-ray diffraction. Biological studies of complexes 2 and 3 had been carried out in vitro for antimicrobial activity against Gram-positive, Gram-negative bacteria and human pathogenic fungi. Compound 3 was proven to be a broad spectrum agent, showed a significant inhibition of the growth of Gram-positive bacteria (Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, Micrococcus luteus), and pathogenic fungi (Candida spp., Cryptococcus neoformans, Rhodothece glutinis, Saccharomyces cerevisia, Aspergillus spp., Rhizopus nigricans) tested and a moderate activity against Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Enterobacter aerogenes) tested. The in vitro cytotoxicity of compound 3 was evaluated using hemolytic assay, in which the compound 3 was found to be non-toxic to human erythrocytes even at a concentration of 500mug/mL.

Bacteria↗
PubMed2006

How to promote sluggish electrocyclization of 1,3,5-hexatrienes by captodative substitution.

Hexatriene electrocyclization, if not disfavored by its harsh reaction conditions, can be highly useful for the synthesis of complex organic molecules. Herein we developed a two-layer ONIOM method which could predict the activation free energy of hexatriene electrocyclization with an accuracy of about 1.0 kcal/mol. Using this carefully benchmarked method, we calculated the activation free energies for a variety of substituted hexatrienes. It was found that extraordinarily rapid electrocyclization could occur for certain patterns of captodative substituted hexatrienes, including 2-acceptor-3-donor hexatrienes, 2-acceptor-5-donor hexatrienes, and 3-acceptor-5-donor hexatrienes. The activation free energies for these systems could be up to 10 kcal/mol lower than that of the unsubstituted hexatriene, and therefore, their electrocyclization could proceed smoothly even at room temperature. The mechanism for the captodative effect on hexatriene electrocyclization could be understood by calculating the affinity between the donor and acceptor group in the reactant state and transition state of the reaction. If the affinity was stronger in the transition state, captodative substitution would produce an extra acceleration effect. It was shown that our theoretical results were in excellent agreement with the experimental data from the recent synthetic studies of hexatriene electrocyclizations. Thus, the theoretical tools developed in the present study could be used to predict not only how to accelerate the hexatriene electrocyclization via substituent manipulation but also under what conditions each particular electrocyclization could be accomplished in the real experiment.

Cyclization↗
PubMed2006

S-nitrosylating agents: a novel class of compounds that increase cystic fibrosis transmembrane conductance regulator expression and maturation in epithelial cells.

The endogenous bronchodilator, S-nitrosoglutathione (GSNO), increases expression, maturation, and function of both the wild-type and the DeltaF508 mutant of the cystic fibrosis transmembrane conductance regulatory protein (CFTR). Though transcriptional mechanisms of action have been identified, GSNO seems also to have post-transcriptional effects on CFTR maturation. Here, we report that 1) GSNO is only one of a class of S-nitrosylating agents that, at low micromolar concentrations, increase DeltaF508 and wild-type CFTR expression and maturation; 2) NO itself (at these concentrations) and 8-bromocyclic GMP are minimally active on CFTR; 3) a novel agent, S-nitrosoglutathione diethyl ester, bypasses the need for GSNO bioactivation by gamma-glutamyl transpeptidase to increase CFTR maturation; 4) surprisingly, expression-but not S-nitrosylation-of cysteine string proteins (Csp) 1 and 2 is increased by GSNO; 5) the effect of GSNO to increase full maturation of wild-type CFTR is inhibited by Csp silencing (si)RNA; 6) proteins relevant to CFTR trafficking are SNO-modified, and SNO proteins traffic through the endoplasmic reticulum (ER) and Golgi after GSNO exposure; and 7) GSNO alters the interactions of DeltaF508 CFTR with Csp and Hsc70 in the ER and Golgi. These data suggest that GSNO is one of a class of S-nitrosylating agents that act independently of the classic NO radical/cyclic GMP pathway to increase CFTR expression and maturation. They also suggest that the effect of GSNO is dependent on Csp and on intracellular SNO trafficking. We speculate that these data will be of relevance to the development of NO donor-based therapies for CF.

Cell Differentiation↗
PubMed2006

Significant effects of phosphorylation on relative stabilities of DNA and RNA sugar radicals: remarkably high susceptibility of h-2' abstraction in RNA.

The roles of nucleic acid radicals in DNA and RNA damage cannot be properly understood in the absence of knowledge of the C-H bond strengths depicting the energy cost to generate each of these radicals. However, previous theoretical studies on the relative energies of different nucleic acid radicals are not fully convincing mainly because of the use of oversimplified model compounds. In the present study we chose nucleoside 3',5'-bisphosphates as model compounds for DNA and RNA, in which the effects of both the nucleobase and phosphorylation were taken into consideration. Using the newly developed ONIOM-G3B3 methods, we calculated the gas-phase bond dissociation enthalpies and solution-phase bond dissociation free energies of all the carbohydrate C-H bonds in the model compounds. It was found that the monoanionic phosphate group (OPO3H-) was a better radical stabilization group than the OH group by 1.3 kcal/mol, whereas the neutral phosphate group (OPO3H2) was a significantly worse radical stabilization group than OH by 4.4 kcal/mol. Due to these reasons, the relative thermodynamic susceptibility of H-abstraction from deoxyribonucleotides and ribonucleotides varied considerably depending on the phosphorylation state and the charge carried by the phosphate groups. Strikingly, the bond dissociation free energy of C2'-H in ribonucleotides was dramatically lower than that of all the other C-H bonds by 5-6 kcal/mol regardless of the phosphorylation state and the charge carried by the phosphate group. This explained the previous experimental finding that radiation damage of RNA occurs mainly via H-abstraction at H-2'. A model study suggested that the strength of the hydrogen bonding interaction between the 2'-OH and 3-phosphate groups should dramatically increase from ribonucleoside 3',5'-bisphosphate to its C2' radical. The strengthened hydrogen bonding stabilized the C2' radical, rendering the C2'-H bond of RNA extraordinarily vulnerable to H-abstraction.

Carbohydrates↗
PubMed2006

U1-like snRNAs lacking complementarity to canonical 5' splice sites.

We have detected a surprising heterogeneity among human spliceosomal U1 small nuclear RNA (snRNA). Most interestingly, we have identified three U1 snRNA variants that lack complementarity to the canonical 5' splice site (5'SS) GU dinucleotide. Furthermore, we have observed heterogeneity among the identified variant U1 snRNA genes caused by single nucleotide polymorphism (SNP). The identified snRNAs were ubiquitously expressed in a variety of human tissues representing different stages of development and displayed features of functional spliceosomal snRNAs, i.e., trimethylated cap structures, association with Sm proteins and presence in nuclear RNA-protein complexes. The unanticipated heterogeneity among spliceosomal snRNAs could contribute to the complexity of vertebrates by expanding the coding capacity of their genomes.

Base Pairing↗
PubMed2006

Configuration-dependent interface charge transfer at a molecule-metal junction.

The role of the molecule-metal interface is a key issue in molecular electronics. Interface charge transfer processes for 4-fluorobenzenethiol monolayers with different molecular orientations on Au(111) were studied by resonant photoemission spectroscopy. The electrons excited into the LUMO or LUMO+1 are strongly localized for the molecules standing up on Au(111). In contrast, an ultrafast charge transfer process was observed for the molecules lying down on Au(111). This configuration-dependent ultrafast electron transfer is dominated by an adiabatic mechanism and directly reflects the delocalization of the molecular orbitals for molecules lying down on Au(111). Theoretical calculations confirm that the molecular orbitals indeed experience a localization-delocalization transition resulting from hybridization between the molecular orbitals and metal surface. Such an orientation-dependent transition could be harnessed in molecular devices that switch via charge transfer when the molecular orientation is made to change.

Journal Article↗
PubMed2006

N,N-dimethyl-beta-alanine as an inexpensive and efficient ligand for palladium-catalyzed Heck reaction.

N,N-Dimethyl-beta-alanine was found to be a more powerful phosphine-free ligand than the previously reported ligand, N,N-dimethylglycine, in the Pd-catalyzed Heck reaction for a variety of aryl bromides, aryl iodides, and activated aryl chlorides with a practical turnover number of 10(3). Both kinetic and theoretical studies suggested that N,N-dimethyl-beta-alanine led to faster oxidative addition of an aryl halide to Pd than N,N-dimethylglycine. [reaction: see text]

Catalysis↗
PubMed2006

Low ligand loading, highly enantioselective addition of phenylacetylene to aromatic ketones catalyzed by Schiff-base amino alcohols.

[reaction: see text] Schiff-base amino alcohols 7a,b derived from L-phenylglycine through three simple steps are found to be highly effective for the enantioselective addition of phenylacetylene to aromatic ketones. When the loading of 7b was 1 mol %, an ee value of up to 95% was obtained. However, when 7b was lowered to 0.1 mol %, a high ee value of 85% was still achieved. A practical solution to synthesize the optically active tertiary propargylic alcohols was described.

Journal Article↗
PubMed2006

Pluripotency potential of human adipose-derived stem cells marked with exogenous green fluorescent protein.

Musculoskeletal tissues regeneration requires rapid expansion of seeding cells both in vitro and in vivo while maintaining their multilineage differentiation ability. Human adipose-derived stem cells (ASCs) are considered to contain multipotent mesenchymal stem cells. Monolayer cultures of human ASCs were isolated from human lipoaspirates and passaged 3 times and then infected with replication-incompetent adenoviral vectors carrying green fluorescent protein (Ad/GFP) genes. Then, Ad/GFP infected human ASCs were transferred to osteogenic, chondrogenic, adipogenic, and myogenic medium. The morphological characterization of induced cells was observed using phase-contrast microscopy and fluorescence microscopy. The expression of marker proteins or genes was measured by immunocytochemical and RT-PCR analysis. Osteopontin (OPN), and osteocalcin (OCN) were positive in osteogenic lineages, aggrecan and SOX9 were positive in chondrogenic ones, peroxisome proliferator-activated receptor (PPAR-gamma2) and lipoprotein lipase (LPL) were positive in adipogenic ones, and myogenin and myod1 was positive in myogenic ones. At the same time, the results of fluorescence microscopic imaging proved that the high level of GFP expression during ASCs differentiation maintained stable nearly 2 months. So the exogenous GFP and multilineage potential of human ASCs had no severe influences on each other. Since the human ASCs can be easily obtained and abundant, it is proposed that they may be promising candidate cells for further studies on tissue engineering. Imaging with expression of GFP facilitates the research on ASCs physiological behavior and application in tissue engineering during differentiation both in vitro and in vivo.

Adenoviridae↗
PubMed2006

Quantum-chemical predictions of redox potentials of organic anions in dimethyl sulfoxide and reevaluation of bond dissociation enthalpies measured by the electrochemical methods.

A first-principle theoretical protocol was developed that could predict the absolute pK(a) values of over 250 structurally unrelated compounds in DMSO with a precision of 1.4 pK(a) units. On this basis we developed the first theoretical protocol that could predict the standard redox potentials of over 250 structurally unrelated organic anions in DMSO with a precision of 0.11 V. Using the two new protocols we systematically reevaluated the bond dissociation enthalpies (BDEs) measured previously by the electrochemical methods. It was confirmed that for most compounds the empirical equation (BDE = 1.37 pK(HA) + 23.1E(o) + constant) was valid. The constant in this equation was determined to be 74.0 kcal/mol, compared to 73.3 kcal/mol previously reported. Nevertheless, for a few compounds the empirical equation could not be used because the solvation energy changed dramatically during the bond cleavage, which resulted from the extraordinary change of dipole moment during the reaction. In addition, we found 40 compounds (mostly oximes and amides) for which the experimental values were questionable by over 5 kcal/mol. Further analyses revealed that all these questionable BDEs could be explained by one of the three following reasons: (1) the experimental pK(a) value is questionable; (2) the experimental redox potential is questionable; (3) the solvent effect cannot be neglected. Thus, by developing practical theoretical methods and utilizing them to solve realistic problems, we hope to demonstrate that ab initio theoretical methods can now be developed to make not only reliable, but also useful, predictions for solution-phase organic chemistry.

Anions↗
PubMed2006

Exploring photosynthesis evolution by comparative analysis of metabolic networks between chloroplasts and photosynthetic bacteria.

BACKGROUND: Chloroplasts descended from cyanobacteria and have a drastically reduced genome following an endosymbiotic event. Many genes of the ancestral cyanobacterial genome have been transferred to the plant nuclear genome by horizontal gene transfer. However, a selective set of metabolism pathways is maintained in chloroplasts using both chloroplast genome encoded and nuclear genome encoded enzymes. As an organelle specialized for carrying out photosynthesis, does the chloroplast metabolic network have properties adapted for higher efficiency of photosynthesis? We compared metabolic network properties of chloroplasts and prokaryotic photosynthetic organisms, mostly cyanobacteria, based on metabolic maps derived from genome data to identify features of chloroplast network properties that are different from cyanobacteria and to analyze possible functional significance of those features. RESULTS: The properties of the entire metabolic network and the sub-network that consists of reactions directly connected to the Calvin Cycle have been analyzed using hypergraph representation. Results showed that the whole metabolic networks in chloroplast and cyanobacteria both possess small-world network properties. Although the number of compounds and reactions in chloroplasts is less than that in cyanobacteria, the chloroplast's metabolic network has longer average path length, a larger diameter, and is Calvin Cycle -centered, indicating an overall less-dense network structure with specific and local high density areas in chloroplasts. Moreover, chloroplast metabolic network exhibits a better modular organization than cyanobacterial ones. Enzymes involved in the same metabolic processes tend to cluster into the same module in chloroplasts. CONCLUSION: In summary, the differences in metabolic network properties may reflect the evolutionary changes during endosymbiosis that led to the improvement of the photosynthesis efficiency in higher plants. Our findings are consistent with the notion that since the light energy absorption, transfer and conversion is highly efficient even in photosynthetic bacteria, the further improvements in photosynthetic efficiency in higher plants may rely on changes in metabolic network properties.

Arabidopsis↗