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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↗
PubMed2007

Osteogenic differentiation of adipose derived stem cells promoted by overexpression of osterix.

Adipose-derived stem cells (ASCs) are considered to be multipotent mesenchymal stem cells that are easily induced to differentiate into functional osteoblasts both in vitro and in vivo. Osterix (Osx) is a zinc finger-containing transcription factor of Sp gene family, which plays important roles in bone development and mineralization. In this study, we hypothesized that overexpression of Osx in murine ASCs would promote their osteogenic differentiation in vitro. A plasmid expressing Osx (pcDNA3.1-Osx) was constructed and applied to transfect monolayers of murine ASCs. Then expression of bone-related genes, nodule formation, proliferation rate, and alkaline phosphatase activity were examined to evaluate the osteogenic potential of ASCs with pcDNA3.1-Osx transfection. Results of RT-PCR and immunohistochemistry showed that pcDNA3.1-Osx transfection enhanced the expression of bone matrix proteins, such as bone sialoprotein, osteocalcin, osteopontin, and Collagen type I in ASCs. At the same time, overexpression of Osx in ASCs enhanced alkaline phosphatase activity and capability to form mineralized nodules, while not inhibited their proliferation rate. These results indicated that pcDNA3.1-Osx transfection promoted the osteogenic differentiation of ASCs, while not affecting their proliferative ability. Since they can be easily isolated and genetically modified, ASCs are hopeful cell sources in the further application of hard tissue engineering.

Adipose Tissue↗
PubMed2007

Plant-microbe association for rhizoremediation of chloronitroaromatic pollutants with Comamonas sp. strain CNB-1.

Comamonas sp. strain CNB-1, isolated from activated sludge and having a strong ability to degrade 4-chloronitrobenzene (4CNB), was applied for rhizoremediation of 4CNB-polluted soil through association with alfalfa. Confocal laser scanning microscopy revealed that strain CNB-1 successfully colonized alfalfa roots. Determination of strain CNB-1 populations by cultivation method and by quantitative competitive PCR technique targeting the chloronitrobenzene nitroreductase gene showed that the population of strain CNB-1 in the rhizosphere was about 10-100 times higher than that in the bulk soil. Gnotobiotic and outdoor experiments showed that pollutant 4CNB was completely removed within 1 or 2 days after 4CNB application into soil, and that its phytotoxicity to alfalfa was eliminated by inoculation of strain CNB-1. Results from PCR-denaturing gradient gel electrophoresis and analysis of 16S rRNA gene libraries revealed that the indigenous soil microbial community mainly consisted of alphaproteobacteria, betaproteobacteria, gammaproteobacteria, the CFB bacteria (Cytophaga-Flavabacterium-Bacteriodes), and Acidobacteria. This microbial community was not significantly influenced by inoculation of strain CNB-1. Thus, this study has developed a Comamonas-alfalfa system for rhizoremediation of 4CNB.

Biodegradation, Environmental↗
PubMed2007

Fluorescence resonance energy transfer analysis of bid activation in living cells during ultraviolet-induced apoptosis.

Ultraviolet (UV) irradiation is a DNA-damaging agent that triggers apoptosis through both the membrane death receptor and mitochondrial apoptotic signaling pathways. Bid, a pro-apoptotic Bcl-2 family member, is important in most cell types to apoptosis in response to DNA damage. In this study, a recombinant plasmid, YFP-Bid-CFP, comprised of yellow and cyan fluorescent protein and a full length Bid, was used as a fluorescence resonance energy transfer analysis (FRET) probe. Using the FRET technique based on YFP-Bid-CFP, we found that Bid activation was initiated at 9+/-1 h after UV irradiation, and the average duration of the activation was 75+/-10 min. Bid activation coincided with a collapse of the mitochondrial membrane potential with an average duration of 50+/-10 min. When cells were pretreated with Z-IETD-fmk (caspase-8 specific inhibitor) the process of Bid activation was completely inhibited, but the apoptosis was only partially affected. Z-DEVD-fmk (caspase-3 inhibitor) and Z-FA-fmk (non asp specific inhibitor) did not block Bid activation. Furthermore, the endogenous Bid activation with or without Z-IETD-fmk in response to UV irradiation was confirmed by Western blotting. In summary, using the FRET technique, we observed the dynamics of Bid activation during UV-induced apoptosis and found that it was a caspase-8 dependent event.

Apoptosis↗
PubMed2007

[Alteration in serum cytokines of patients with multiple organ dysfunction syndrome after liver transplantation].

OBJECTIVE: To explore the serum cytokine fluctuation in those adult patients with multiple organ dysfunction syndrome (MODS) during the post-operation stage of orthotopic liver transplantation (OLT) to guide the clinical treatment. METHODS: Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-8 and IL-10 were determined in 53 MODS patients who had received OLT. They were divided into two groups as control group and experimental group, according to whether continuous blood purification (CBP) had been performed or not. The levels of serum cytokines and intensive care unit (ICU) stay time, intubation time, mortality and ICU expenses were compared between the two groups. RESULTS: The levels of serum TNF-alpha, IL-6 and IL-8 rose, while that of IL-10 increased dramatically compared with normal values (all P<0.05). After CBP, the serum levels of TNF-alpha, IL-6 and IL-8 all dropped to certain extent and became lower than those before the treatment (all P<0.05). IL-10's serum level was not changed compared with that before treatment. Those who received CBP stayed in the ICU for a longer period compared with control group, and the ICU expenses increased evidently with significant differences (P<0.05 or P<0.01). However, there was no difference in mortality between the two groups. CONCLUSION: Under the effect of immunosuppressant in the post-OLT period, the excessive release of the anti-inflammatory mediators may become dominant leading to imbalance between proinflammatory and anti-inflammatory mediators leading to MODS. CBP may remove serum proinflammatory cytokines to act as an effective supportive treatment.

Adult↗
PubMed2007

Preparation and physicochemical properties of scaffold materials of heterogeneous deproteinized bone.

OBJECTIVE: To prepare and observe the physicochemical properties of scaffold materials of heterogeneous deproteinized tissue-engineered bone. METHODS: Deproteinized bone was made through a series of physicochemical treatments in pig ribs and analyzed with histological observation, scanning electron microscopy, infrared spectrum, X-ray diffraction and energy dispersive analysis, Kjeldahl determination and mechanics analysis. RESULTS: Interstitial collagen fiber was positive and mucin was negative in deproteinized bone, but, both were positive in fresh bone. Deproteinized bone maintained natural pore network. Its pore size was 472.51 micromolar+/-7.02 micromolar and the porosity was 78.15%+/-6.45%. The results of infrared spectrum showed that collagen was present in deproteinized bone. Both fresh and deproteinized bone had curve of hydroxyapatite. The Ca/P ratios were 1.71+/-0.95 and 1.68+/-0.76 (P larger than 0.05), and the protein contents were 26.6%+/-2.23% and 19.1%+/-2.14% (P less than 0.05) in fresh and deproteinized bone, respectively. There was no significant difference of destruction load under compression and maximal destruction load between fresh and deproteinized bone (P larger than 0.05). The elastic modulus was higher in deproteinized bone than that in fresh bone (P less than 0.05). CONCLUSIONS: Physicochemical properties and mechanic strength of deproteinized tissue-engineered bone meet the demands of ideal scaffold materials. But, its immunogenicity should be observed through further experiments for its clinical applications.

Animals↗
PubMed2006

Kinetic and cardiovascular effects of acute topiramate dosing among non-treatment-seeking, methamphetamine-dependent individuals.

Previously, we have shown that orally administered topiramate, a sulfamate-substituted fructopyranose derivative, appears to accentuate rather than diminish some aspects of methamphetamine-induced positive subjective mood and cognitive performance. One possible mechanism by which this might occur would be for topiramate to increase plasma methamphetamine level. Such an effect also would be expected to enhance methamphetamine-induced hemodynamic response. We, therefore, studied -- in the same experiment from which the previous findings originated -- the effects of topiramate on the kinetic profile and hemodynamic response to methamphetamine. In a 27-day inpatient study, 10 methamphetamine-dependent individuals participated in a double-blind, placebo-controlled, cross-over design, with oral doses of topiramate (0, 100, and 200 mg) administered as a pretreatment before intravenous doses of methamphetamine (0, 15, and 30 mg). The 3x3 factorial combination of topiramate and methamphetamine resulted in a sequence of the nine treatments administered to each subject in an order determined by a 9x9 Latin Square design. Methamphetamine alone was associated with prototypical increases in hemodynamic response that were not altered in the presence of topiramate. While there was no significant kinetic interaction between topiramate and methamphetamine, there was a non-significant trend for topiramate to increase plasma methamphetamine level. No significant adverse events were reported. The combination of topiramate and methamphetamine at pharmacologically relevant doses appears to be safe. Larger laboratory studies with chronic dosing regimens are needed to establish whether or not there is a kinetic interaction between topiramate and methamphetamine.

Adult↗
PubMed2006

Isoprenoid biosynthesis as a drug target: bisphosphonate inhibition of Escherichia coli K12 growth and synergistic effects of fosmidomycin.

We screened a library of 117 bisphosphonates for antibacterial activity against Escherichia coli. The most potent growth inhibitors where N-[methyl(4-phenylalkyl)]-3-aminopropyl-1-hydroxy-1,1-bisphosphonates, known potent bone resorption inhibitors, and there was a generally good correlation between cell growth inhibition and E. coli farnesyl diphosphate synthase (FPPS) inhibition. However, some potent FPPS inhibitors had no activity in cell growth inhibition, and based on the result of Catalyst pharmacophore modeling, this could be attributed to the requirement of a large hydrophobic feature for cellular activity (due most likely to transport). The activity of the most potent compound, N-[methyl(4-phenylbutyl)]-3-aminopropyl-1-hydroxy-1,1-bisphosphonate (13), was strongly potentiated by the drug fosmidomycin. The transcription profiles for 13 or fosmidomycin alone were different from those found with carbenicillin or ciprofloxacin alone, but there were many similarities between the combination (13-fosmidomycin) and carbenicillin or ciprofloxacin, reflecting the more potent bactericidal activity of the drug combination on bacterial growth.

Anti-Bacterial Agents↗
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

Buffering airway acid decreases exhaled nitric oxide in asthma.

BACKGROUND: The human airway is believed to be acidified in asthma. In an acidic environment nitrite is converted to nitric oxide (NO). OBJECTIVE: We hypothesized that buffering airway lining fluid acid would decrease the fraction of exhaled NO (F(ENO)). METHODS: We treated 28 adult nonsmoking subjects (9 healthy control subjects, 11 subjects with mild intermittent asthma, and 8 subjects with persistent asthma) with 3 mL of 10 mmol/L phosphate buffered saline (PBS) through a nebulizer and then serially measured F(ENO) levels. Six subjects also received PBS mouthwash alone. RESULTS: F(ENO) levels decreased after buffer inhalation. The maximal decrease occurred between 15 and 30 minutes after treatment; F(ENO) levels returned to pretreatment levels by 60 minutes. The decrease was greatest in subjects with persistent asthma (-7.1 +/- 1.0 ppb); this was more than in those with either mild asthma (-2.9 +/- 0.3 ppb) or healthy control subjects (-1.7 +/- 0.3 ppb, P < .001). Levels did not decrease in subjects who used PBS mouthwash. CONCLUSION: Neutralizing airway acid decreases F(ENO) levels. The magnitude of this change is greatest in persistent asthma. These data suggest that airway pH is a determinant of F(ENO) levels downstream from NO synthase activation. CLINICAL IMPLICATIONS: Airway biochemistry modulates F(ENO) levels. For example, nitrite is converted to NO in the airway, particularly the inflamed airway, by means of acid-based chemistry. Thus airway pH should be considered in interpreting clinical F(ENO) values. In fact, PBS challenge testing integrates airway pH and F(ENO) analysis, potentially improving the utility of F(ENO) as a noninvasive test for the type and severity of asthmatic airway inflammation.

Acids↗
PubMed2006

Electrochemical analysis of the effect of Ca2+ on cardiolipin-cytochrome c interaction.

Mitochondrial Ca2+ has been considered a trigger for the release of cytochrome c, which is a critical and early event in the induction of cell apoptosis, although the molecular mechanism underlying this effect is still not fully understood. Here we investigate the interaction between cytochrome c and cardiolipin and the effect of Ca2+ on this interaction using electrochemical methods. Experimental results revealed that modification of cardiolipin onto the surface of a pyrolytic graphite electrode could lead to a rapid direct electron transfer of cytochrome c through the electrostatic interaction between the protein and the cardiolipin. Addition of Ca2+ to the test solution containing cytochrome c could cause the decrease of the redox peaks of the protein, and the peaks could be recovered when Ca2+ was chelated by ethylenediaminetetraacetate. The cardiolipin-cytochrome c interaction and the Ca2+ effect were also investigated with the variation of the charges of lipids, buffer solutions, reaction time, and valencies of cations for comparison.

Animals↗
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↗