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Biomedical subjects

Ge Wang

Publications and source records attributed to Ge Wang.

At least 19 recordsLinked to original sources

Engineering local nitrogen coordination environments of Palladium subnanometric clusters in metal-organic frameworks for efficient hydrogenation.

Subnanometric clusters (SCs) bridge the gap between single-atom catalysts and nanoparticles by combining high atomic utilization with cooperative multi-atom effects. However, stabilizing low-coordinated SCs while maintaining accessible active sites remains challenging. Here, we introduce pyrazole-3,5-dicarboxylic acid (PZDC), pyridine-3,5-dicarboxylic acid (PDC), and pyrrole-3,5-dicarboxylic acid (PPy) as secondary ligands in metal-organic frameworks to regulate the local nitrogen (N) coordination environment of Pd SCs (∼0.6 nm). Specifically, PZDC provides a chemically differentiated pyrazolic dual-N environment containing formally pyridinic-like and pyrrolic-like N sites. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (AC HAADF-STEM) and X-ray absorption spectroscopy (XAS) confirm the formation of low-coordinated Pd clusters containing PdN and PdPd interactions, while CO diffuse reflectance infrared Fourier transform spectroscopy (CO-DRIFTS) reveals a distinctive adsorption environment characterized by geminal dicarbonyl species and strongly suppressed bridge-bonded CO adsorption. Within this catalyst series, the PZDC-functionalized material exhibits the highest activity and tetrahydrocyclopentadiene (THDCPD) selectivity in dicyclopentadiene (DCPD) hydrogenation. These results demonstrate that modification of the local N environment can regulate the average coordination structure, adsorption behavior, and catalytic properties of MOF-supported Pd SCs.

Hydrogenation catalysis↗

Controlled framework nickel exsolution in metal-organic frameworks creates confined active sites for chemoselective citral hydrogenation.

Selective hydrogenation of citral to citronellal over non-noble-metal catalysts remains challenging because highly active metallic Ni simultaneously promotes efficient substrate activation and undesired over‑hydrogenation of the desired product. Herein, we develop a controlled exsolution strategy in waste polyethylene terephthalate (PET)-derived nickel metal-organic frameworks (Ni-MOFs) to transform framework Ni into confined metallic active sites while preserving the porous framework architecture. During reductive treatment, framework Ni2+ species undergo gradual node-to-metal evolution, generating highly dispersed Ni0 sites confined within the partially retained MOF framework. More importantly, the degree of framework Ni exsolution governs the balance between citral activation and citronellal over‑hydrogenation, thereby establishing a distinct chemoselective window. Within the optimal exsolution regime, the framework-confined Ni0 sites enable efficient H2 activation and selective hydrogenation of the CC bond while suppressing the subsequent hydrogenation of citronellal. Consequently, the optimized catalyst achieves ∼99% citral conversion and 100% citronellal selectivity at 90 °C and 2 MPa H2, together with excellent catalytic stability and recyclability. Beyond the sustainable valorization of waste PET, this work establishes controlled framework exsolution as an effective strategy for engineering confined active sites and regulating chemoselectivity in non-noble-metal hydrogenation catalysts.

Chemoselective hydrogenation↗

Numerical study on the validity of the diffusion approximation for computational optical biopsy.

Currently, we are developing a computational optical biopsy technology for molecular sensing. We use the diffusion equation to model photon propagation but have a concern about the accuracy of diffusion approximation when the optical sensor is close to a bioluminescent source. We derive formulas to describe photon fluence for point and ball sources and measurement formulas for an idealized optical biopsy probe. Then, we numerically compare the diffusion approximation and the radiative transport as implemented by Monte Carlo simulation in the cases of point and ball sources. Our simulation results show that the diffusion approximation can be accurately applied if mu's>>mu(a) even if the sensor is very close to the source (>1mm). Furthermore, an approximate formula is given to describe the measurement of a cut-end fiber probe for a ball source.

Biomedical Research↗

Bolus characteristics based on Magnetic Resonance Angiography.

BACKGROUND: A detailed contrast bolus propagation model is essential for optimizing bolus-chasing Computed Tomography Angiography (CTA). Bolus characteristics were studied using bolus-timing datasets from Magnetic Resonance Angiography (MRA) for adaptive controller design and validation. METHODS: MRA bolus-timing datasets of the aorta in thirty patients were analyzed by a program developed with MATLAB. Bolus characteristics, such as peak position, dispersion and bolus velocity, were studied. The bolus profile was fit to a convolution function, which would serve as a mathematical model of bolus propagation in future controller design. RESULTS: The maximum speed of the bolus in the aorta ranged from 5-13 cm/s and the dwell time ranged from 7-13 seconds. Bolus characteristics were well described by the proposed propagation model, which included the exact functional relationships between the parameters and aortic location. CONCLUSION: The convolution function describes bolus dynamics reasonably well and could be used to implement the adaptive controller design.

Computer Simulation↗

A general exact method for synthesizing parallel-beam projections from cone-beam projections via filtered backprojection.

In recent years, image reconstruction methods for cone-beam computed tomography (CT) have been extensively studied. However, few of these studies discussed computing parallel-beam projections from cone-beam projections. In this paper, we focus on the exact synthesis of complete or incomplete parallel-beam projections from cone-beam projections. First, an extended central slice theorem is described to establish a relationship between the Radon space and the Fourier space. Then, data sufficiency conditions are proposed for computing parallel-beam projection data from cone-beam data. Using these results, a general filtered backprojection algorithm is formulated that can exactly synthesize parallel-beam projection data from cone-beam projection data. As an example, we prove that parallel-beam projections can be exactly synthesized in an angular range in the case of circular cone-beam scanning. Interestingly, this angular range is larger than that derived in the Feldkamp reconstruction framework. Numerical experiments are performed in the circular scanning case to verify our method.

Algorithms↗

Dual Roles of Helicobacter pylori NapA in inducing and combating oxidative stress.

Neutrophil-activating protein (NapA) has been well documented to play roles in human neutrophil recruitment and in stimulating host cell production of reactive oxygen intermediates (ROI). A separate role for NapA in combating oxidative stress within H. pylori was implied by studies of various H. pylori mutant strains. Here, physiological analysis of a napA strain was the approach used to assess the iron-sequestering and stress resistance roles of NapA, its role in preventing oxidative DNA damage, and its importance to mouse colonization. The napA strain was more sensitive to oxidative stress reagents and to oxygen, and it contained fourfold more intracellular free iron and more damaged DNA than the parent strain. Pure, iron-loaded NapA bound to DNA, but native NapA did not, presumably linking iron levels sensed by NapA to DNA damage protection. Despite its in vitro phenotype of sensitivity to oxidative stress, the napA strain showed normal (like that of the wild type) mouse colonization efficiency in the conventional in vivo assay. By use of a modified mouse inoculation protocol whereby nonviable H. pylori is first inoculated into mice, followed by (live) bacterial strain administration, an in vivo role for NapA in colonization efficiency could be demonstrated. NapA is the critical component responsible for inducing host-mediated ROI production, thus inhibiting colonization by the napA strain. An animal colonization experiment with a mixed-strain infection protocol further demonstrated that the napA strain has significantly decreased ability to survive when competing with the wild type. H. pylori NapA has unique and separate roles in gastric pathogenesis.

Animals↗

Role of a MutY DNA glycosylase in combating oxidative DNA damage in Helicobacter pylori.

MutY is an adenine glycosylase that has the ability to efficiently remove adenines from adenine/7,8-dihydro-8-oxoguanine (8-oxo-G) or adenine/guanine mismatches, and plays an important role in oxidative DNA damage repair. The human gastric pathogen Helicobacter pylori has a homolog of the MutY enzyme. To investigate the physiological roles of MutY in H. pylori, we constructed and characterized a mutY mutant. H. pylori mutY mutants incubated at 5% O2 have a 325-fold higher spontaneous mutation rate than its parent. The mutation rate is further increased by exposing the mutant to atmospheric levels of oxygen, an effect that is not seen in an E. coli mutY mutant. Most of the mutations that occurred in H. pylori mutY mutants, as examined by rpoB sequence changes that confer rifampicin resistance, are GC to TA transversions. The H. pylori enzyme has the ability to complement an E. coli mutY mutant, restoring its mutation frequency to the wild-type level. Pure H. pylori MutY has the ability to remove adenines from A/8-oxo-G mismatches, but strikingly no ability to cleave A/G mismatches. This is surprising because E. coli MutY can more rapidly turnover A/G than A/8-oxo-G. Thus, H. pylori MutY is an adenine glycosylase involved in the repair of oxidative DNA damage with a specificity for detecting 8-oxo-G. In addition, H. pylori mutY mutants are only 30% as efficient as wild-type in colonizing the stomach of mice, indicating that H. pylori MutY plays a significant role in oxidative DNA damage repair in vivo.

Amino Acid Sequence↗

A novel deletion in TNNI2 causes distal arthrogryposis in a large Chinese family with marked variability of expression.

Distal arthrogryposis (DA) is composed of a group of clinically and genetically heterogeneous disorders, characterized by multiple congenital contractures of the limbs. Point mutations in three genes encoding contractile fast-twitch myofibers, TPM2, TNNI2 and TNNT3, were recently identified in DA type 1 (DA1; MIM 108120) and DA type 2B (DA2B; MIM 601680). We have described a large Chinese DA family in which different individuals had phenotypes similar to DA1 or DA2B. To map the disease locus in this family, two-point linkage analysis was first performed using microsatellite markers selected from the genomic regions close to the TPM2, TNNI2/TNNT3 and TNNC2 genes. A positive LOD score of 3.61 at theta = 0 was obtained with the marker close to the TNNI2/TNNT3 genes, corresponding to the genetic mapping site of DA2B. Direct sequencing of the PCR-amplified DNA fragment spanning exon 8 of the TNNI2 gene showed a heterozygous deletion, c.523_525delAAG (p.K175del), in the proband. This novel mutation was confirmed to cosegregate with the DA phenotype in affected individuals but not detected in all unaffected individuals of the family and not in 50 healthy controls. In summary, we have found a novel TNNI2 mutation in a Chinese family with DA2B. Our work represents the first report on the link between TNNI2 and the DA phenotype in Chinese.

Arthrogryposis↗

Lipid peroxidation as a source of oxidative damage in Helicobacter pylori: protective roles of peroxiredoxins.

Oxidative stress conditions lead to enzymatic and non-enzymatic unsaturated fatty acid-initiated lipid peroxidation reactions. One exacerbating product is lipid hydroperoxide (LOOH) which itself promotes formation of several additional peroxyl radicals. Helicobacter pylori mutant strains with disruptions in genes encoding the peroxiredoxins, alkyl hydroperoxide reductase (ahpC) and the bacterioferritin comigratory protein (bcp), were more sensitive than the parent strain to oxidizing agents. These mutant strains were particularly sensitive, compared to the wild type, to killing by the unsaturated fatty acid linolenic acid but were not sensitive to the saturated fatty acid palmitic acid. A double mutant strain (ahpC bcp) accumulated more than 3-fold more lipid peroxides than the parent strain, indicating these peroxiredoxins together play a role in detoxifying lipid peroxides. The level of free iron accumulation, a signature of oxidative stress damage, was correlated specifically to organic peroxide-mediated stress by both in vivo and in vitro approaches. Free iron accumulation and concomitant destruction of [Fe-S] cluster-containing proteins (hydrogenase and aconitase) was correlated to damage mediated by exogenous t-butyl peroxide, or separately to intracellular accumulation of lipid peroxides in mutant strains. A major macromolecular target of accumulating lipid peroxides in H. pylori is DNA, as mutant analysis approaches combined with quantitative DNA fragmentation studies and specific DNA damage assessment (i.e. 8-oxoguanine formation) were used to demonstrate that such damage was especially associated with ahpC and ahpC bcp strains.

Bacterial Proteins↗

Reduction of half-scan shading artifact based on full-scan correction.

RATIONALE AND OBJECTIVES: Temporal studies (such as blood perfusion) commonly are used to measure function. Radiation dosage is a primary limiting factor for these scans. Half-scan reconstruction can decrease dosage and improve temporal resolution, but is not viable for quantitative studies because of shading artifact. We propose a method for identifying the artifact and minimizing its effect. MATERIALS AND METHODS: It is possible to measure the shading artifact by producing both a full-scan and a half-scan reconstruction from the same projection data. A correlation was shown between the subset of data used for reconstruction and per-pixel variation. Furthermore, this variation can be parameterized by only the center angle of the projection data. By performing a single full-scan acquisition, it is possible to generate many half-scan reconstructions and measure the artifact; then future half-scan acquisitions can be corrected. RESULTS: The artifact is caused by the inhomogeneity in the object being scanned. Before correction, the root mean square error between the half-scan reconstruction and the full-scan is 41.0. After correction, the error is decreased to 10.7, or 26% of the original value. CONCLUSION: We present a method that can measure and correct for object-dependent half-scan shading artifact. This can enable half-scan reconstruction for use in quantitative temporal studies.

Algorithms↗

Helicobacter hepaticus Dps protein plays an important role in protecting DNA from oxidative damage.

The ferritin-like DNA-binding protein from starved cells (Dps) family proteins are present in a number of pathogenic bacteria. Dps in the enterohepatic pathogen, Helicobacter hepaticus is characterized and a H. hepaticus dps mutant was generated by insertional mutagenesis. While the wild type H. hepaticus cells were able to survive in an atmosphere containing up to 6.0% O2, the dps mutant failed to grow in 3.0% O2, and it was also more sensitive to oxidative reagents like H2O2, cumene hydroperoxide and t-butyl hydroperoxide. Upon air exposure, the dps- cells had more damaged DNA than the wild type; they became coccoid or lysed and they contained approximately 6-fold higher amount of 8-oxoguanine (8-oxoG) DNA lesions than wild type cells. Purified H. hepaticus Dps was shown to be able to bind both iron and DNA. The iron-loaded form of Dps protein had much greater DNA binding ability than the native Dps or the iron-free Dps.

Bacterial Proteins↗

Data consistency based translational motion artifact reduction in fan-beam CT.

A basic assumption in the classic computed tomography (CT) theory is that an object remains stationary in an entire scan. In biomedical CT/micro-CT, this assumption is often violated. To produce high-resolution images, such as for our recently proposed clinical micro-CT (CMCT) prototype, it is desirable to develop a precise motion estimation and image reconstruction scheme. In this paper, we first extend the Helgason-Ludwig consistency condition (HLCC) from parallel-beam to fan-beam geometry when an object is subject to a translation. Then, we propose a novel method to estimate the motion parameters only from sinograms based on the HLCC. To reconstruct the moving object, we formulate two generalized fan-beam reconstruction methods, which are in filtered backprojection and backprojection filtering formats, respectively. Furthermore, we present numerical simulation results to show that our approach is accurate and robust.

Algorithms↗

The diverse antioxidant systems of Helicobacter pylori.

The gastric pathogen Helicobacter pylori induces a strong inflammatory host response, yet the bacterium maintains long-term persistence in the host. H. pylori combats oxidative stress via a battery of diverse activities, some of which are unique or newly described. In addition to using the well-studied bacterial oxidative stress resistance enzymes superoxide dismutase and catalase, H. pylori depends on a family of peroxiredoxins (alkylhydroperoxide reductase, bacterioferritin co-migratory protein and a thiol-peroxidase) that function to detoxify organic peroxides. Newly described antioxidant proteins include a soluble NADPH quinone reductase (MdaB) and an iron sequestering protein (NapA) that has dual roles - host inflammation stimulation and minimizing reactive oxygen species production within H. pylori. An H. pylori arginase attenuates host inflammation, a thioredoxin required as a reductant for many oxidative stress enzymes is also a chaperon, and some novel properties of KatA and AhpC were discovered. To repair oxidative DNA damage, H. pylori uses an endonuclease (Nth), DNA recombination pathways and a newly described type of bacterial MutS2 that specifically recognizes 8-oxoguanine. A methionine sulphoxide reductase (Msr) plays a role in reducing the overall oxidized protein content of the cell, although it specifically targets oxidized Met residues. H. pylori possess few stress regulator proteins, but the key roles of a ferric uptake regulator (Fur) and a post-transcriptional regulator CsrA in antioxidant protein expression are described. The roles of all of these antioxidant systems have been addressed by a targeted mutant analysis approach and almost all are shown to be important in host colonization. The described antioxidant systems in H. pylori are expected to be relevant to many bacterial-associated diseases, as genes for most of the enzymes carrying out the newly described roles are present in a number of pathogenic bacteria.

Animals↗

A born-type approximation method for bioluminescence tomography.

In this paper, we present a Born-type approximation method for bioluminescence tomography (BLT), which is to reconstruct an internal bioluminescent source from the measured bioluminescent signal on the external surface of a small animal. Based on the diffusion approximation for the photon propagation in biological tissue, this BLT method utilizes the Green function to establish a linear relationship between the measured bioluminescent signal and the internal bioluminescent source distribution. The Green function can be modified to describe a heterogeneous medium with an arbitrary boundary using the Born approximation. The BLT reconstruction is formulated in a linear least-squares optimization framework with simple bounds constraint. The performance of this method is evaluated in numerical simulation and phantom experiments.

Algorithms↗

Cone-beam mammo-computed tomography from data along two tilting arcs.

Over the past several years there has been an increasing interest in cone-beam computed tomography (CT) for breast imaging. In this article, we propose a new scheme for theoretically exact cone-beam mammo-CT and develop a corresponding Katsevich-type reconstruction algorithm. In our scheme, cone-beam scans are performed along two tilting arcs to collect a sufficient amount of information for exact reconstruction. In our algorithm, cone-beam data are filtered in a shift-invariant fashion and then weighted backprojected into the three-dimensional space for the final reconstruction. Our approach has several desirable features, including tolerance of axial data truncation, efficiency in sequential/parallel implementation, and accuracy for quantitative analysis. We also demonstrate the system performance and clinical utility of the proposed technique in numerical simulations.

Algorithms↗

Practical cone-beam lambda tomography.

As a potentially important technology for medical x-ray computed tomography (CT), lambda tomography (LT) is to reconstruct a gradient-like image only from local projection data. Based on our recently derived exact fan-beam LT formula, [H. Y. Gu and G. Wang, Int. J. Biomed. Imaging 2006(1), 1-9 (2006)] here we propose a practical cone-beam LT algorithm for LT reconstruction from local data collected along an arbitrary smooth three-dimensional curve. A key step in our algorithm is to determine an appropriate vector perpendicular to the line connecting the x-ray source and an image point. The algorithm is implemented assuming an equispatial planar detector and a nonstandard spiral trajectory. The numerical simulation results demonstrate the merits of our method.

Algorithms↗

[Construction and identification of a multiple myeloma-specific APE1 siRNA expression vector].

OBJECTIVE: To construct a multiple myeloma (MM)-specific APE1siRNA expression vector, and detect the specific knock-down effect of the siRNA on expression of APE1 protein. METHODS: APE1siRNA cDNA sequence was designed, synthesized and inserted into pSilencer 2.0-U6 linear expression vector. pSilencer APE1siRNA was digested by enzyme EcoRI and BamHI, then linear vector and IgP fragments were conjugated by T4 DNA ligase. pSilencer IgP-APE1siRNA and pSilencer IE-IgP-APE1siRNA were digested by enzyme EcoRI or XhoI. Linear vector and IE or Kappa fragments were conjugated by T4 DNA ligase. Then a MM specific pSilencer K-IE-IgP-APE1siRNA was cloned. The recombinant products were identified by DNA sequencing and enzyme digestions at each step. pSilencer K-IE-IgP-APE1siRNA plasmid was transfected to KM3, HOS, MDA-231 cells by liposome. APE1 gene silence induced by RNAi was analysed by Western blot. RESULTS: APE1 protein in KM3 cells could be knocked down effectively and specifically by pSilencer K-IE-IgP-APE1siRNA vector. After 2 days, the level of APE1 protein in KM3 cells transfected with siRNA was 0.118 +/- 0.047, while that transfected with plasmid only was 0.988 +/- 0.029. The efficiency of gene silence was 90%. CONCLUSION: A MM specific APE1siRNA expression vector was successfully constructed.

Base Sequence↗