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Biomedical subjects

Liping Wang

Publications and source records attributed to Liping Wang.

At least 19 recordsLinked to original sources

Bibliometric analysis of retinoblastoma research over the past decade.

BACKGROUND: Retinoblastoma (RB), the most prevalent primary intraocular malignancy in children, has emerged as a model disease for exploring the molecular underpinnings of pediatric cancer. Over the past decade, research in this field has accelerated, propelled by advances in genomics, diagnostic imaging, targeted therapies, and global scientific collaboration. METHODS: This study systematically retrieved RB-related publications from 2015 to 2024 using the Web of Science Core Collection. A total of 4990 articles were included. CiteSpace and VOSviewer were employed to perform bibliometric and visual analyses across multiple dimensions, including countries, institutions, authors, journals, and thematic evolution. RESULTS: The United States and China were identified as the leading contributors, jointly accounting for over 40.55% of all publications. US-based journals led in both publication volume and citation impact, underscoring their global influence. Cluster analysis revealed 4 major research domains: clinical diagnosis, treatment, and prognosis; molecular mechanisms and signaling pathways; gene and protein function studies; and research methodologies and experimental models. CONCLUSION: RB research is transitioning into an era of precision oncology, characterized by molecular subtyping, novel therapeutic targets, and individualized treatment approaches. While diagnostic and therapeutic outcomes have markedly improved in high-income countries, significant disparities persist in low- and middle-income regions due to limited access to early detection and comprehensive care. Future priorities should include the refinement of preclinical models, investigation of drug resistance mechanisms, and promotion of international collaboration to standardize diagnostic and therapeutic strategies. These efforts are critical to improving global outcomes for children with RB.

Retinoblastoma↗

AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset.

Genetic intervention is increasingly being explored as a therapeutic option for debilitating disorders of the central nervous system. The safety and efficacy of gene therapies rely upon expressing a transgene in affected cells while minimizing off-target expression. Here we show organ-specific targeting of adeno-associated virus (AAV) capsids after intravenous delivery, which we achieved by employing a Cre-transgenic-based screening platform and sequential engineering of AAV-PHP.eB between the surface-exposed AA452 and AA460 of VP3. From this selection, we identified capsid variants that were enriched in the brain and targeted away from the liver in C57BL/6J mice. This tropism extends to marmoset (Callithrix jacchus), enabling robust, non-invasive gene delivery to the marmoset brain after intravenous administration. Notably, the capsids identified result in distinct transgene expression profiles within the brain, with one exhibiting high specificity to neurons. The ability to cross the blood-brain barrier with neuronal specificity in rodents and non-human primates enables new avenues for basic research and therapeutic possibilities unattainable with naturally occurring serotypes.

Administration, Intravenous↗

Crystallization of protein-ligand complexes.

Obtaining diffraction-quality crystals has long been a bottleneck in solving the three-dimensional structures of proteins. Often proteins may be stabilized when they are complexed with a substrate, nucleic acid, cofactor or small molecule. These ligands, on the other hand, have the potential to induce significant conformational changes to the protein and ab initio screening may be required to find a new crystal form. This paper presents an overview of strategies in the following areas for obtaining crystals of protein-ligand complexes: (i) co-expression of the protein with the ligands of interest, (ii) use of the ligands during protein purification, (iii) cocrystallization and (iv) soaks.

Animals↗

Determination of four benzodiazepine residues in pork using multiwalled carbon nanotube solid-phase extraction and gas chromatography-mass spectrometry.

A solid-phase extraction (SPE)/GC-MS method using multiwalled carbon nanotubes (MWCNTs) was developed for the determination of four benzodiazepine residues including diazepam, estazolam, alprazolam and triazolam in pork. The analytes were extracted by ultrasonic assistant extraction using acetonitrile, concentrated and purified by MWCNTs packed cartridge, and determined by GC-MS. Ultrasonic extraction conditions, which included temperature, time, power, and solvent volume, were optimized. Comparative studies showed that MWCNTs were superior to C18 for the adsorption of drugs. Parameters influencing SPE efficiency, such as sample amounts, variety and volume of the eluent, were also optimized. Electron ionization (EI) operating in time program-selected ion monitoring mode (SIM) was used for GC-MS identification. The analytes were quantified with external standard calibration curve method. Lower limit of detection and quantification was obtained by the new method. Linear calibration curves were obtained in the concentration range from 10 ng/mL to 500 ng/mL for diazepam and from 20 ng/mL to 1000 ng/mL for estazolam, alprazolam and triazolam with calibration coefficients of 0.99 and above. The average recoveries for the four benzodiazepines spiked in pork were 75% to 104% and their relative standard deviations were between 1.3% and 10%. The limits of detection were 2 microg/kg for diazepam and 5 microg/kg for estazolam, alprazolam and triazolam in pork, respectively.

Adsorption↗

Relationships between three-body and two-body interactions in fluids and solids.

Molecular dynamics data are reported for two-body and three-body interactions in noble gases at densities covering the gas, liquid, and solid phases. The data indicate that simple relationships exist between three- and two-body interactions in both fluid and solid phases. The relationship for liquids has a simple density dependence with only one external parameter. In contrast, the solid phase relationship depends both on density and on the square of density and requires the evaluation of two parameters. The relationships are tested for both system-size and temperature dependences. The values of the relationship parameters are only sensitive to system size when a small number of atoms are involved. For 500 or more atoms, they remain nearly constant. The relationships are valid for both subcritical and slightly supercritical temperatures. A practical benefit of the relationships is that they enable the use of two-body intermolecular potentials for the prediction of the properties of real systems without the computational expense of three-body calculations.

Journal Article↗

HPLC quantification of sphingolipids in soybeans with modified palmitate content.

Efficient separation and accurate quantification of sphingolipids (SL) are important for studying SL concentrations and biological functions. The objectives of this study were to develop effective methods for the separation and quantification of SL and to determine the relationship between palmitate and SL contents of mature soybean seeds. Methods using column chromatography and high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) were developed to separate and quantify glucosylceramide (GlcCer) and ceramide (Cer) in 15 soybeans lines in which palmitate content ranged from 3.7 to 40.7%. There were significant differences among the lines for GlcCer (83.4-397.6 nmol/g) and major Cer contents (8.4-20.7 nmol/g) on a dry weight basis. The correlations of palmitate content with GlcCer and Cer concentrations were not significant. The results indicated that the palmitate content of soybean seed did not affect their GlcCer and Cer contents. Genetic factors other than those that control palmitate content seemed to be responsible for the variation among soybean lines for GlcCer and Cer contents.

Ceramides↗

Effect of seed development stage on sphingolipid and phospholipid contents in soybean seeds.

Glucosylceramide (GlcCer) and ceramide (Cer) are the predominant sphingolipids (SL) in soybeans. They have been recognized as functional components in plants and may have health benefits for humans. The objective of this study was to evaluate the changes in SL and phospholipid (PL) contents that occurred during seed development. Soybean seeds of three cultivars (IA1008, IA1010, and IA1014) were harvested at 5-day intervals from 28 days after flowering (DAF) to 68 DAF (mature seed). SL and PL contents of seeds were quantified using high-performance liquid chromatography (HPLC) with an evaporative light scattering detector (ELSD). SL and PL contents decreased significantly during seed development. Averaged across cultivars, Cer content on a dry weight basis decreased from 51.4 nmol/g at 28 DAF to 22.2 nmol/g at 68 DAF, whereas GlcCer content decreased from 522.8 nmol/g at 28 DAF to 135.8 nmol/g at 68 DAF. PL percentage of the total lipid decreased from 9.1% at 28 DAF to 3.5% at 68 DAF.

Ceramides↗

X-ray crystal structures of the estrogen-related receptor-gamma ligand binding domain in three functional states reveal the molecular basis of small molecule regulation.

X-ray crystal structures of the ligand binding domain (LBD) of the estrogen-related receptor-gamma (ERRgamma) were determined that describe this receptor in three distinct states: unliganded, inverse agonist bound, and agonist bound. Two structures were solved for the unliganded state, the ERRgamma LBD alone, and in complex with a coregulator peptide representing a portion of receptor interacting protein 140 (RIP140). No significant differences were seen between these structures that both exhibited the conformation of ERRgamma seen in studies with other coactivators. Two structures were obtained describing the inverse agonist-bound state, the ERRgamma LBD with 4-hydroxytamoxifen (4-OHT), and the ERRgamma LBD with 4-OHT and a peptide representing a portion of the silencing mediator of retinoid and thyroid hormone action protein (SMRT). The 4-OHT structure was similar to other reported inverse agonist bound structures, showing reorientation of phenylalanine 435 and a displacement of the AF-2 helix relative to the unliganded structures with little other rearrangement occurring. No significant changes to the LBD appear to be induced by peptide binding with the addition of the SMRT peptide to the ERRgamma plus 4-OHT complex. The observed agonist-bound state contains the ERRgamma LBD, a ligand (GSK4716), and the RIP140 peptide and reveals an unexpected rearrangement of the phenol-binding residues. Thermal stability studies show that agonist binding leads to global stabilization of the ligand binding domain. In contrast to the conventional mechanism of nuclear receptor ligand activation, activation of ERRgamma by GSK4716 does not appear to involve a major rearrangement or significant stabilization of the C-terminal helix.

Binding Sites↗

Three-body interactions and solid-liquid phase equilibria: application of a molecular dynamics algorithm.

The effect of three-body interactions on the solid-liquid phase boundaries of argon, krypton, and xenon is investigated via a novel technique that combines both nonequilibrium and equilibrium molecular dynamics. The simulations involve the evaluation of two- and three-body forces using accurate two-body and three-body intermolecular potentials. The effect of three-body interactions is to substantially increase the coexistence pressure and to lower the densities of liquid and solid phases. Comparison with experiment indicates that three-body interactions are required to accurately determine the total pressure. In contrast to vapor-liquid phase equilibria, the relative contribution of three-body interactions to the freezing pressure exceeds the contribution of two-body interactions at all temperatures.

Journal Article↗

Influence of two-body and three-body interatomic forces on gas, liquid, and solid phases.

Accurate molecular dynamics simulations are reported which quantify the contributions of two- and three-body interactions in the gas, liquid, and solid phases of argon at both subcritical and supercritical conditions. The calculations use an accurate two-body potential in addition to contributions from three-body dispersion interactions from third-order triple-dipole interactions. The number dependence of three-body interactions is quantified, indicating that a system size of at least five hundred atoms is required for reliable calculations. The results indicate that, although the contribution of three-body interaction to the overall energy is small, three-body interactions significantly affect the pressure at which vapor-liquid and solid-liquid transitions are observed. In particular, three-body interactions substantially increase the pressure of the freezing point. Unlike two-body interactions, which vary with both density and temperature, for a given density, three-body interactions have a near-constant 'background' value irrespective of the temperature. Both two-body interactions and kinetic energy have an important role in vapor-liquid equilibria whereas solid-liquid equilibria are dominated by two-body interactions.

Journal Article↗

Effect of three-body interactions on the vapor-liquid phase equilibria of binary fluid mixtures.

Gibbs-Duhem Monte Carlo simulations are reported for the vapor-liquid phase coexistence of binary argon+krypton mixtures at different temperatures. The calculations employ accurate two-body potentials in addition to contributions from three-body dispersion interactions resulting from third-order triple-dipole interactions. A comparison is made with experiment that illustrates the role of three-body interactions on the phase envelope. In all cases the simulations represent genuine predictions with input parameters obtained independently from sources other than phase equilibria data. Two-body interactions alone are insufficient to adequately describe vapor-liquid coexistence. In contrast, the addition of three-body interactions results in very good agreement with experiment. In addition to the exact calculation of three-body interactions, calculations are reported with an approximate formula for three-body interactions, which also yields good results.

Journal Article↗

Simultaneous determination of three residual barbiturates in pork using accelerated solvent extraction and gas chromatography-mass spectrometry.

A new method was developed for the rapid extraction and unequivocal determination of barbital, amobarbital and phenobarbital residues in pork. The isolation of the analytes from pork samples was accomplished by utilizing an accelerated solvent extractor ASE 300. The procedure was automatically carried out in series for fat removing and extraction, respectively with n-hexane and acetonitrile pressurized constantly at 10.3 MPa for 30 min. After evaporation, the extracts were cleaned up on a C(18) solid phase extraction (SPE) cartridge and the barbiturates were eluted with hexane-ethyl acetate (7:3), evaporated on a rotary evaporator and derivatized with CH(3)I. The methylated barbiturates were separated on a HP-5MS capillary column and detected with a mass detector. Electron impact ion source (EI) operating in time program-selected ion monitoring mode (SIM) was used for identification and external standard method was used for quantification. Good linearity was obtained in the range from 0.5 microg/kg to 25 microg/kg. Average recoveries of the three barbiturates spiked in pork ranged from 84.0% to 103.0%, with relative standard deviations from 1.6% to 12%. The limit of detection (LOD) was 0.5 microg/kg for the three barbiturates (S/N>or=3). The quantification limit (LOQ) was 1 microg/kg for the three barbiturates (S/N>or=10).

Animals↗

Electrochemical studies of the interaction of the anticancer herbal drug emodin with DNA.

The interaction between anticancer herbal drug emodin and DNA was studied with differential pulse voltammetry (DPV) and cyclic voltammetry (CV) at the bare or DNA modified GCE and ultraviolet-visible (UV) spectra. The DPV of emodin showed that peak potentials shifted to more positive value and peak currents decreased with the addition of DNA. UV spectra exhibited that the absorption of emodin at about 440nm decreased with red shift. The results showed that the herbal drug emodin interacted with DNA by intercalating into the double helix of DNA. Under our experiment conditions, the decrease of peak current was proportional to DNA concentration, which can be applied to determining DNA concentration. The combining constant (beta) and combing number (m) of DNA-mEM were determined too.

Antineoplastic Agents, Phytogenic↗

Acute behavioural stress facilitates long-term depression in temporoammonic-CA1 pathway.

Behavioural stress facilitates long-term depression in Schaffer collaterals-CA1 pathway, but it is unknown whether it influences long-term depression in temporoammonic fibres-CA1. Here, we report that low-frequency stimulation induced long-term depression and foot shock stress before slice preparation facilitated long-term depression in both pathways of young rat slices. When the field excitatory postsynaptic potentials were recorded by stimulating the two pathways alternately and low-frequency stimulation was given to the two pathways simultaneously, a reliable long-term depression was induced in Schaffer collaterals-CA1 but a reliable long-term potentiation took place in temporoammonic fibres-CA1. Interestingly, foot shock stress now enabled low-frequency stimulation to induce reliable long-term depressions in both pathways. These findings suggested that acute behavioural stress facilitated long-term depressions in both pathways and disrupted the interactions between pathways.

Animals↗

Integrin beta1 silencing in osteoblasts alters substrate-dependent responses to 1,25-dihydroxy vitamin D3.

Surface microroughness increases osteoblast differentiation and enhances responses of osteoblasts to 1,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3]. The observations that beta1 integrin expression is increased in osteoblasts grown on Ti substrates with rough microarchitecture, and that it is regulated by 1alpha,25(OH)2D3 in a surface-dependent manner, suggest that beta1 may play a role in mediating osteoblast response. To test this hypothesis, we silenced beta1 expression in MG63 human osteoblast-like cells using small interfering RNA (siRNA) and examined the responses of the beta1-silenced osteoblasts to surface microtopography and 1alpha,25(OH)2D3. To better understand the role of beta1, MG63 cells were also treated with two different monoclonal antibodies to human beta1 to block ligand binding. beta1-silenced MG63 cells grown on a tissue culture plastic had reduced alkaline phosphatase activity and levels of osteocalcin, transforming growth factor beta1, prostaglandin E2, and osteoprotegerin in comparison with control cells. Moreover, beta1-silencing inhibited the effects of surface roughness on these parameters and partially inhibited effects of 1alpha,25(OH)2D3. Anti beta1 antibody AIIB2 had no significant effect on cell number and osteocalcin, but decreased alkaline phosphatase; MAB2253Z caused dose-dependent decreases in cell number and alkaline phosphatase and an increase in osteocalcin. Effects of 1alpha,25(OH)2D3 on cell number and alkaline phosphatase were reduced and effects on osteocalcin were increased. These findings indicate that beta1 plays a major and complex role in osteoblastic differentiation modulated by either surface microarchitecture or 1alpha,25(OH)2D3. The results also show that beta1 mediates, in part, the synergistic effects of surface roughness and 1alpha,25(OH)2D3.

Animals↗

The pH-dependence of photochemical intermediates of O and P in bacteriorhodopsin by continuous light.

The pH-dependence of the O and P intermediates in the photocycle of bacteriorhodopsin (bR) on the intensity and duration of the exciting flash was investigated for bR glycerol suspensions and bR gelatin films. Green and red laser flashes (532 and 670 nm) were utilized to generate a photoequilibrium state of bR and O at ambient temperature, and UV-vis spectroscopy was used to determine the photoconversion for the bR suspensions and films. The maximal concentration of the O intermediate was observed to be pH-dependent and the dependency was most pronounced at a slightly alkaline pH values. The photochemical conversion from the O to P intermediate was investigated for both bR suspensions and films. The P intermediate was only found in bR gelatin film. These results indicate that bR gelatin film may be an attractive candidate for the information storage based on P intermediate. It is possible, with red light, to create photoproducts which are thermally stable at ambient temperature and that can be photochemically erased.

Bacteriorhodopsins↗

D-Aspartate as a putative cell-cell signaling molecule in the Aplysia californica central nervous system.

The content, synthesis and transport of D-aspartate (D-Asp) in the CNS of Aplysia californica is investigated using capillary electrophoresis (CE) with both laser-induced fluorescence and radionuclide detection. Millimolar concentrations of D-Asp are found in various regions of the CNS. In the cerebral ganglion, three adjacent neuronal clusters have reproducibly different D-Asp levels; for example, in the F- and C-clusters, up to 85% of the free Asp is present in the D-form. Heterogeneous distribution of D-Asp is also found in the individual identified neurons tested, including the optical ganglion top-layer neurons, metacerebral cells, R2 neurons, and F-, C- and G-cluster neurons. The F-cluster neurons have the highest percentage of D-Asp (approximately 58% of the total Asp), whereas the lowest value of approximately 8% is found in R2 neurons. In pulse-chase experiments with radiolabeled D-Asp, followed by CE with radionuclide detection, the synthesis of D-Asp from L-aspartate (L-Asp) is confirmed. Is D-Asp in the soma, or is it transported to distantly located release sites? D-Asp is clearly detected in the major nerves of A. californica, including the pleuroabdominal and cerebrobuccal connectives and the anterior tentacular nerves, suggesting it is transported long distances. In addition, both D-Asp and L-Asp are transported in the pleuroabdominal connectives in a colchicine-dependent manner, whereas several other amino acids are not. Finally, d-Asp produces electrophysiological effects similar to those induced by L-Asp. These data are consistent with an active role for D-Asp in cell-to-cell communication.

Animals↗

Type-2 cells as link between glial and neuronal lineage in adult hippocampal neurogenesis.

In the course of adult hippocampal neurogenesis, new cells go through a series of stages associated with proliferative activity. The most highly proliferative cell type is an intermediate precursor cell, called type-2 cell. We here report that on the level of type-2 cells a transition takes place between features associated with the glial and the neuronal lineage. We show that stem-cell marker Sox2 and radial glia marker BLBP are expressed in type-2 cells but label only a small percentage of the proliferating cells. By and large, precursor cell marker Sox2 was found to be widely expressed in hippocampal astrocytes. Between 3 h and 1 week after a single injection of permanent S-phase marker bromodeoxyuridine (BrdU), the number of BrdU-labeled BLBP-positive cells did not change, consistent with the idea that both markers here are associated with the maintained precursor cell pool. Using reporter gene mice expressing the green fluorescent protein (GFP) under the promoter for nestin we found an overlap of GFP with markers of the neuronal lineage, doublecortin (DCX) and transcription factor NeuroD1 in type-2 cells, whereas in glial fibrillary acidic protein (GFAP)-GFP mice expression of GFP and NeuroD1 or DCX was mutually exclusive. Electrophysiologically, the group of type-2 cells fell into two subgroups: one with astrocytic properties and another with an early "complex" phenotype of neural progenitor cells. Our data further support the existence of proliferative precursor cells that mark the transition between glia-like states and neuronal differentiation.

Animals↗