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Xiaofeng Liu

Publications and source records attributed to Xiaofeng Liu.

At least 19 recordsLinked to original sources
PubMed2026

Integrative single-cell and genomic analysis reveals NMB as a driver of metastatic adaptation in esophageal squamous cell carcinoma via metabolic rewiring and immune evasion.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has high mortality, and metastasis is the leading cause of patient death. Neuromedin B (NMB) promotes tumor development in various cancers, yet its role in ESCC metastasis remains unclear. METHODS: We integrated single-cell transcriptomic data from matched primary and metastatic ESCC lesions (GSE309392) with bulk transcriptomic cohorts from TCGA and GSE53624. In silico gene perturbation, ligand-receptor communication analysis, and single-cell prognostic model construction were performed, followed by functional validation through siRNA-mediated NMB knockdown in TE-1 and KYSE30 cell lines. RESULTS: NMB was identified as a key gene enriched in metastatic ESCC lesions, and its high expression was associated with coordinated upregulation of oxidative phosphorylation pathway genes and aldo-keto reductase family antioxidant enzymes (AKR1C1, AKR1C2, AKR1B10). Genomic analysis revealed that NMB-high tumors carried a higher clonal mutation burden and a markedly increased frequency of NFE2L2 activating mutations (23% vs. 8%, P = 0.04). In silico knockout and correlation analysis identified AKR1C1 as a downstream effector of NMB. NMB expression was negatively correlated with CD8+ T cell and activated NK cell infiltration. CellChat analysis revealed communication between NMB-positive cells and monocytes via the TGM2-ADGRG1 axis, and specifically detected IFNG signaling. In the single-cell prognostic model, NMB-positive cells accounted for 50% of the high-risk group but only 20% of the low-risk group. TCGA-based survival analysis demonstrated that high NMB expression was associated with shorter overall survival (HR = 2.98, P = 0.03). In vitro NMB-targeted RNA interference markedly inhibited proliferation, colony formation, and migration in TE-1 and KYSE30 cells. CMap screening identified the endothelin-PDE5-cGMP axis as a potential therapeutic target. CONCLUSION: NMB serves as a key driver of metastatic adaptation in ESCC, conferring a survival advantage to tumor cells during metastatic colonization through genomic evolution and immune remodeling, with metabolic adaptation as a downstream consequence of genomic alterations.

NMB↗
PubMed2006

Synthesis, characterization, and self-assembly of nitrogen-containing heterocoronenetetracarboxylic acid diimide analogues: photocyclization of N-heterocycle-substituted perylene bisimides.

Novel dibenzocoronenetetracarboxylic acid diimide analogues and naphthoperylenetetracarboxylic acid diimide analogues containing imidazole, 1,2,4-triazole, and pyrazole rings embedded as functional constituents within the parent hydrocarbon backbone have been synthesized. The pi-rich and pi-poor heterocycles have different influences on the physical properties of the parent benzocoronenetetracarboxylic acid diimide and naphthoperylenetetracarboxylic acid diimide systems. The pi-rich 3 was able to self-assemble into one-dimensional nanostructures through strong pi-pi stacking, whereas the pi-poor 8 lacked the one-dimensional self-assembly capability, thus offering the potential to control the self-assembly capability of the pi-conjugated perylene core by decoration with N-heterocycles.

Journal Article↗
PubMed2006

Ferritins: iron/oxygen biominerals in protein nanocages.

Ferritin protein nanocages that form iron oxy biominerals in the central nanometer cavity are nature's answer to managing iron and oxygen; gene deletions are lethal in mammals and render bacteria more vulnerable to host release of antipathogen oxidants. The multifunctional, multisubunit proteins couple iron with oxygen (maxi-ferritins) or hydrogen peroxide (mini-ferritins) at catalytic sites that are related to di-iron sites oxidases, ribonucleotide reductase, methane monooxygenase and fatty acid desaturases, and synthesize mineral precursors. Gated pores, distributed symmetrically around the ferritin cages, control removal of iron by reductants and chelators. Gene regulation of ferritin, long known to depend on iron and, in animals, on a noncoding messenger RNA (mRNA) structure linked in a combinatorial array to functionally related mRNA of iron transport, has recently been shown to be linked to an array of proteins for antioxidant responses such as thioredoxin and quinone reductases. Ferritin DNA responds more to oxygen signals, and ferritin mRNA responds more to iron signals. Ferritin genes (DNA and RNA) and protein function at the intersection of iron and oxygen chemistry in biology.

Catalysis↗
PubMed2006

Paired Bacillus anthracis Dps (mini-ferritin) have different reactivities with peroxide.

Dps (DNA protection during starvation) proteins, mini-ferritins in the ferritin superfamily, catalyze Fe(2+)/H(2)O(2)/O(2) reactions and make minerals inside protein nanocages to minimize radical oxygen-chemistry (metal/osmotic/temperature/nutrient/oxidant) and sometimes to confer virulence. Paired Dps proteins in Bacillus, rare in other bacteria, have 60% sequence identity. To explore functional differences in paired Bacilli Dps protein, we measured ferroxidase activity and DNA protection (hydroxyl radical) for Dps protein dodecamers from Bacillus anthracis (Ba) since crystal structures and iron mineralization (iron-stain) were known. The self-assembled (200 kDa) Ba Dps1 (Dlp-1) and Ba Dps2 (Dlp-2) proteins had similar Fe(2+)/O(2) kinetics, with space for minerals of 500 iron atoms/protein, and protected DNA. The reactions with Fe(2+) were novel in several ways: 1) Ba Dps2 reactions (Fe(2+)/H(2)O(2)) proceeded via an A(650 nm) intermediate, with similar rates to maxi-ferritins (Fe(2+)/O(2)), indicating a new Dps protein reaction pathway, 2) Ba Dps2 reactions (Fe(2+)/O(2) versus Fe(2+)/O(2) + H(2)O(2)) differed 3-fold contrasting with Escherichia coli Dps reactions, with 100-fold differences, and 3) Ba Dps1, inert in Fe(2+)/H(2)O(2) catalysis, inhibited protein-independent Fe(2+)/H(2)O(2) reactions. Sequence similarities between Ba Dps1 and Bacillus subtilis DpsA (Dps1), which is regulated by general stress factor (SigmaB) and Fur, and between Ba Dps2 and B. subtilis MrgA, which is regulated by H(2)O(2) (PerR), suggest the function of Ba Dps1 is iron sequestration and the function of Ba Dps2 is H(2)O(2) destruction, important in host/pathogen interactions. Destruction of H(2)O(2) by Ba Dps2 proceeds via an unknown mechanism with an intermediate similar spectrally (A(650 nm)) and kinetically to the maxi-ferritin diferric peroxo complex.

Amino Acid Sequence↗
PubMed2006

A rapid reversed phase high-performance liquid chromatographic method for determination of sophoridine in rat plasma and its application to pharmacokinetics studies.

A high-performance liquid chromatography (HPLC) method for determining sophoridine in rat plasma was developed for application in the pharmacokinetic studies. The plasma was deproteinized with acetonitrile that contained an internal standard (ephedrine) and was separated from the aqueous layer by adding sodium chloride and sodium carbonate. The HPLC assay was carried out using a YMC-ODS column. The mobile phase was methanol-ethanol-0.01 moll(-1) ammonium acetate buffer-triethylamine (10:0.5:89.5:0.03, v/v/v/v) (pH 6.80). The flow rate was 0.8 ml min(-1). The detection wavelength was set at 210 nm. The method was used to determine the concentration-time profiles of sophoridine in the plasma following oral administration or injection of sophoridine aqueous solution. The fractions of sophoridine reaching the systemic circulation were estimated for the first time by a deconvolution method.

Alkaloids↗
PubMed2006

A versatile synthesis of 17-heteroaryl androstenes via palladium-mediated Suzuki cross-coupling with heteroaryl boronic acids.

Suzuki coupling of 17-iodoandrosta-5,16-dien-3beta-ol (1) and 17-iodoandrosta-4,16-dien-3-one (2) with nine heteroaryl boronic acids (mainly 2- or 3-furanyl, thienyl, benzofuranyl and benzothienyl boronic acid derivatives) were carried out under normal Suzuki condition (Pd(PPh(3))(4), 2M Na(2)CO(3) and MeOH), generally yielded C(17)-heteroaryl steroids in moderate (10-60%) yields, but furanyl-2- and 5-chlorothienyl-2-boronic acid did not give any coupling product.

Androstenes↗
PubMed2006

Dual-function cinchona alkaloid catalysis: catalytic asymmetric tandem conjugate addition-protonation for the direct creation of nonadjacent stereocenters.

Catalytic tandem asymmetric reactions constitute a powerful strategy for the asymmetric construction of nonadjacent stereocenters in acyclic molecules directly from achiral precursors. In this Communication, we report a highly enantioselective and diastereoselective addition of trisubstituted carbon donors to 2-chloroacrylonitrile catalyzed by bifunctional cinchona alkaloid catalysts. This represents the first asymmetric tandem conjugate addition-protonation with efficient catalytic control of two nonadjacent stereocenters. As demonstrated in a concise and highly stereoselective formal total synthesis of (-)-manzacidin A, this asymmetric tandem reaction establishes a new and versatile catalytic approach for the enantioselective and diastereoselective creation of 1,3-tertiary-quaternary stereocenters.

Acrylonitrile↗
PubMed2006

Iron absorption from soybean ferritin in nonanemic women.

BACKGROUND: Dietary ferritin, a protein cage around an iron mineral, is an underestimated source of bioavailable iron. Plant ferritin, the most common dietary ferritin, has not been studied. Iron from animal ferritin is absorbed as well as is iron from FeSO4 in women. OBJECTIVE: The objective was to examine iron absorption from purified soybean ferritin. DESIGN: Healthy, nonanemic women (n = 16) were fed a standardized meal (bagel, cream cheese, and apple juice) containing 1 microCi 59Fe/meal as FeSO4 or (extrinsically labeled) as iron-free soybean ferritin reconstituted with the high phosphate characteristic of plant ferritin (iron:phosphorus = 4:1). Iron-free, apo-soybean ferritin was prepared (with the use of thioglycolic acid and extensive dialysis) from purified ferritin. In a randomized crossover design, the other labeled meal, which contained FeSO4 or ferritin, was given after 4 wk. The subjects received 140 microg Fe as ferritin (2.5 mg) or as FeSO4. After 28 d, whole-body 59Fe and 59Fe in red blood cells were measured before and after dosing. RESULTS: There was no significant difference in whole-body iron absorption from soybean ferritin (29.9 +/- 19.8%) and that from FeSO4 (34.3 +/- 23.6%) or in iron absorption calculated from red blood cell incorporation (33.0 +/- 20.1% for soybean ferritin and 35.3 +/- 23.4% for FeSO4), which confirmed previous results with animal ferritin that was mineralized and labeled similarly. An inverse relation was observed between serum ferritin and iron absorption from both ferritin and FeSO4, which suggested that sensors regulating iron absorption respond similarly to iron provided as ferrous salts or as ferritin mineral. CONCLUSION: Iron from soybean ferritin is well absorbed and may provide a model for novel, utilizable, plant-based forms of iron for populations with a low iron status.

Adult↗
PubMed2005

Wavelet-based estimation of EEG coherence during Chinese Stroop task.

Wavelet-based estimation of instantaneous EEG coherence was applied to investigate the synchronization of different brain regions whilst 10 subjects performing Stroop task presented in Chinese. In contrast to coherence based on Fourier transform, wavelet-based coherence, which does not depend on the stationarity of signals, applies an adaptive window to the frequency of the signal and has a more accurate time-frequency resolution. In the present study, a greater negativity for the incongruent situation than congruent situation appeared from 350 to 600 ms post-stimulus onset over frontal, central, and parietal regions, and significantly higher EEG coherences for the incongruent situation than congruent situation were observed over frontal, parietal, and frontoparietal regions from 100 to 400 ms at beta1 (13-18Hz) frequency band, which was found to be sensitive in the discrimination between congruent and incongruent situations. The findings in the present study may indicate that functional synchronization as indexed by EEG coherence at beta1 frequency band is enhanced at the earlier stage while processing the conflicting information from the incongruent stimulus, and that beta1 frequency band is close related to interactions of brain areas in the selected attention task.

Adult↗
PubMed2005

Catalytic enantioselective C-C bond forming conjugate additions with vinyl sulfones.

In this communication, we describe the development of the first highly enantioselective catalytic conjugate addition to vinyl sulfones. Promoted by readily accessible organocatalysts derived from C6'-OH cinchona alkaloid derivatives and under mild, air- and moisture-tolerant conditions, conjugate additions of a wide range of alpha-cyanoacetates bearing either an alpha-aryl or an alpha-alkyl substituent to vinyl sulfones proceeded in excellent enantioselectivity and high yield. Consequently, this efficient and operationally simple enantioselective C-C bond forming conjugate addition provides a new and useful approach for the enantioselective construction of all-carbon quaternary stereocenters.

Carbon↗
PubMed2005

Highly enantioselective amination of alpha-substituted alpha-cyanoacetates with chiral catalysts accessible from both quinine and quinidine.

[Reaction: see text] The catalytic construction of nitrogen-substituted quaternary stereocenters is an important and challenging task in asymmetric synthesis. In this paper, we describe the use of 6'-OH-modified cinchona alkaloids that are accessible from either quinine or quinidine for the development of a highly enantioselective amination of alpha,alpha-disubstituted carbonyl compounds that is suitable for the creation of nitrogen-substituted quaternary stereocenters in either the R or S configuration.

Journal Article↗
PubMed2005

Ferritins: dynamic management of biological iron and oxygen chemistry.

Ferritins are spherical, cage-like proteins with nanocavities formed by multiple polypeptide subunits (four-helix bundles) that manage iron/oxygen chemistry. Catalytic coupling yields diferric oxo/hydroxo complexes at ferroxidase sites in maxi-ferritin subunits (24 subunits, 480 kDa; plants, animals, microorganisms). Oxidation occurs at the cavity surface of mini-ferritins/Dps proteins (12 subunits, 240 kDa; bacteria). Oxidation products are concentrated as minerals in the nanocavity for iron-protein cofactor synthesis (maxi-ferritins) or DNA protection (mini-ferritins). The protein cage and nanocavity characterize all ferritins, although amino acid sequences diverge, especially in bacteria. Catalytic oxidation/di-iron coupling in the protein cage (maxi-ferritins, 480 kDa; plants, bacteria and animal cell-specific isoforms) or on the cavity surface (mini-ferritins/Dps proteins, 280 kDa; bacteria) initiates mineralization. Gated pores (eight or four), symmetrically arranged, control iron flow. The multiple ferritin functions combine pore, channel, and catalytic functions in compact protein structures required for life and disease response.

Animals↗
PubMed2005

Ferritin as an iron concentrator and chelator target.

Ferritin has a broad role to play in new strategies for managing Cooley's anemia and the thalassemias. Serum ferritin iron content is relegated to reporting on tissue iron concentrations. Recently, a new property of ferritin was discovered: gated pores, which are highly conserved in ferritins of humans down to bacteria, and control iron flow to chelators. The pore gates can be selectively opened to increase chelator access by mutation, temperature, and physiological concentrations of urea. In another recent observation, the iron in ferritin from seeds such as soybeans has been shown to be readily available to tissues with high demand for iron, such as red blood cells, but slower to be mobilized in other tissues, compared to nonheme iron salts, presumably through a controlled iron gating mechanism. Because the iron pore gating property of ferritin is more thoroughly investigated, and the knowledge that much of the iron to be chelated in the thalassemias is from a solid iron mineral inside the ferritin protein nanocage, a new role of ferritin in regulating cellular iron homeostasis is established. Two new areas, based on recent knowledge of the molecular properties of ferritin, are (1) exploration of food ferritin as a potentially safer form of dietary nonheme iron, and (2) development of chelators targeted to ferritin protein pores that control chelator access.

Binding Sites↗
PubMed2005

[Effect of rare-earth element Eu3+ on callus growth and flavonoids content in Glycyrrhiza uralensis].

The effect of rare-earth element Eu3+ on callus growth and its flavonoids content in Glycyrrhiza uralensis was studied. The results showed that lower concentration of rare-earth element Eu3+ could promote the callus growth and flavonoids productions. 0.1 mg/l Eu3+ was the most suitable for the biomass accumulation of the callus and flavonoids biosynthesis. In that concentration flavonoids content was 2.7 times and liquiritigenin was 4 times as that of the control.

Culture Media↗
PubMed2004

Ferritin reactions: direct identification of the site for the diferric peroxide reaction intermediate.

Ferritins managing iron-oxygen biochemistry in animals, plants, and microorganisms belong to the diiron carboxylate protein family and concentrate iron as ferric oxide approximately 10(14) times above the ferric K(s). Ferritin iron (up to 4,500 atoms), used for iron cofactors and heme, or to trap DNA-damaging oxidants in microorganisms, is concentrated in the protein nanocage cavity (5-8 nm) formed during assembly of polypeptide subunits, 24 in maxiferritins and 12 in miniferritins/DNA protection during starvation proteins. Direct identification of ferritin ferroxidase (F(ox)) sites, complicated by multiple types of iron-ferritin interactions, is now achieved with chimeric proteins where putative F(ox) site residues were introduced singly and cumulatively into an inactive host, an L maxiferritin. A dimagnesium ferritin cocrystal model guided site design and the diferric peroxo F(ox) intermediates (A at 650 nm) monitored activity. Diferric peroxo formation in chimeric and WT proteins had similar K(app) values and Hill coefficients. Catalytic activity required cooperative ferrous substrate binding to two sites A (E, EXXH) and B (E, QXXD). The weaker B sites in ferritin contrast with stronger B sites (E, EXXH) in diiron carboxylate oxygenases, explaining diferric oxo/hydroxo product release in ferritin vs. diiron cofactor retention in oxygenases. Codons for Q/H and D/E differ by single nucleotides, suggesting simple DNA mutations relate site B diiron substrate sites and diiron cofactor sites in proteins. The smaller k(cat) values in chimeras indicate the absence of second-shell residues important for ferritin substrate-product channeling that, when identified, will outline the entire iron path from ferritin pores through the F(ox) site to the mineral cavity.

Amino Acid Sequence↗
PubMed2003

Opening protein pores with chaotropes enhances Fe reduction and chelation of Fe from the ferritin biomineral.

Iron is concentrated in ferritin, a spherical protein with a capacious cavity for ferric nanominerals of <4,500 Fe atoms. Global ferritin structure is very stable, resisting 6 M urea and heat (85 degrees C) at neutral pH. Eight pores, each formed by six helices from 3 of the 24 polypeptide subunits, restrict mineral access to reductant, protons, or chelators. Protein-directed transport of Fe and aqueous Fe(3+) chemistry (solubility approximately 10(-18) M) drive mineralization. Ferritin pores are "gated" based on protein crystals and Fe chelation rates of wild-type (WT) and engineered proteins. Pore structure and gate residues, which are highly conserved, thus should be sensitive to environmental changes such as low concentrations of chaotropes. We now demonstrate that urea or guanidine (1-10 mM), far below concentrations for global unfolding, induced multiphasic rate increases in Fe(2+)-bipyridyl formation similar to conservative substitutions of pore residues. Urea (1 M) or the nonconservative LeuPro substitution that fully unfolded pores without urea both induced monophasic rate increases in Fe(2+) chelation rates, indicating unrestricted access between mineral and reductantchelator. The observation of low-melting ferritin subdomains by CD spectroscopy (melting midpoint 53 degrees C), accounting for 10% of ferritin alpha-helices, is unprecedented. The low-melting ferritin subdomains are pores, based on percentage helix and destabilization by either very dilute urea solutions (1 mM) or LeuPro substitution, which both increased Fe(2+) chelation. Biological molecules may have evolved to control gating of ferritin pores in response to cell iron need and, if mimicked by designer drugs, could impact chelation therapies in iron-overload diseases.

Animals↗