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Biomedical subjects

Mingwei Chen

Publications and source records attributed to Mingwei Chen.

9 recordsLinked to original sources

Plasma proteome profiling identifies XPNPEP3 as a novel biomarker associated with metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To identify plasma protein differences between type 2 diabetes mellitus (T2DM) patients with and without metabolic dysfunction-associated steatotic liver disease (MASLD), and to evaluate the diagnostic potential of X-prolyl aminopeptidase 3 (XPNPEP3) for identifying MASLD in T2DM patients. METHODS: Twenty T2DM inpatients were categorized into groups with and without MASLD and their plasma samples were analyzed using data-independent acquisition mass spectrometry, followed by bioinformatics analysis to identify differentially expressed proteins. The cohort was then expanded to 84 patients, and plasma XPNPEP3 levels were validated by enzyme-linked immunosorbent assay. Correlation between XPNPEP3 and clinical indicators were evaluated, and diagnostic performance was determined via receiver operating characteristic (ROC) analysis. Immunohistochemistry was employed to compare hepatic XPNPEP3 expression between the two groups. RESULTS: Proteomic analysis identified 176 differentially expressed proteins, with XPNPEP3 exhibiting the most significant down-regulation by fold change. In the validation cohort, plasma XPNPEP3 was significantly lower in T2DM+MASLD versus T2DM alone. XPNPEP3 levels were negatively correlated with diabetes duration, liver function markers, and triglyceride levels, and was identified as an independent factor inversely associated with MASLD in T2DM.ROC analysis demonstrated strong diagnostic performance for XPNPEP3, further enhanced when combined with BMI and diabetes duration.  Immunohistochemistry confirmed reduced hepatic XPNPEP3 expression in T2DM+MASLD patients. CONCLUSIONS: Lower plasma XPNPEP3 is independently associated with MASLD in T2DM patients and demonstrates strong diagnostic potential, positioning XPNPEP3 as a promising biomarker for diagnosing MASLD in T2DM patients and a novel target for non-invasive diagnostic tool development.

Humans↗

Gefitinib (IRESSA) sensitive lung cancer cell lines show phosphorylation of Akt without ligand stimulation.

BACKGROUND: Phase III trials evaluating the efficacy of gefitinib (IRESSA) in non-small cell lung cancer (NSCLC) lend support to the need for improved patient selection in terms of gefitinib use. Mutation of the epidermal growth factor receptor (EGFR) gene is reported to be associated with clinical responsiveness to gefitinib. However, gefitinib-sensitive and prolonged stable-disease-defined tumors without EGFR gene mutation have also been reported. METHODS: To identify other key factors involved in gefitinib sensitivity, we analyzed the protein expression of molecules within the EGFR family, PI3K-Akt and Ras/MEK/Erk pathways and examined the sensitivity to gefitinib using the MTT cell proliferation assay in 23 lung cancer cell lines. RESULTS: We identified one highly sensitive cell line (PC9), eight cell lines displaying intermediate-sensitivity, and 14 resistant cell lines. Only PC9 and PC14 (intermediate-sensitivity) displayed an EGFR gene mutation including amplification. Eight out of the nine cell lines showing sensitivity had Akt phosphorylation without ligand stimulation, while only three out of the 14 resistant lines displayed this characteristic (P = 0.0059). Furthermore, the ratio of phosphor-Akt/total Akt in sensitive cells was higher than that observed in resistant cells (P = 0.0016). Akt phosphorylation was partially inhibited by gefitinib in all sensitive cell lines. CONCLUSION: These results suggest that Akt phosphorylation without ligand stimulation may play a key signaling role in gefitinib sensitivity, especially intermediate-sensitivity. In addition, expression analyses of the EGFR family, EGFR gene mutation, and FISH (fluorescence in situ hybridization) analyses showed that the phosphorylated state of EGFR and Akt might be a useful clinical marker of Akt activation without ligand stimulation, in addition to EGFR gene mutation and amplification, particularly in adenocarcinomas.

Antineoplastic Agents↗

Extraordinary plasticity of ductile bulk metallic glasses.

Shear bands generally initiate strain softening and result in low ductility of metallic glasses. In this Letter, we report high-resolution electron microscope observations of shear bands in a ductile metallic glass. Strain softening caused by localized shearing was found to be effectively prevented by nanocrystallization that is in situ produced by plastic flow within the shear bands, leading to large plasticity and strain hardening. These atomic-scale observations not only well explain the extraordinary plasticity that was recently observed in some bulk metallic glasses, but also reveal a novel deformation mechanism that can effectively improve the ductility of monolithic metallic glasses.

Journal Article↗

Metallic mesoporous nanocomposites for electrocatalysis.

We describe the fabrication, characterization, and applications of ultrathin, free-standing mesoporous metal membranes uniformly decorated with catalytically active nanoparticles. Platinum-plated nanoporous gold leaf (Pt-NPG) made by confining a plating reaction to occur within the pores of dealloyed silver/gold leaf is 100 nm thick and contains an extremely high, uniform dispersion of 3 nm diameter catalytic particles. This nanostructured composite holds promise as a prototypical member of a new class of fuel cell electrodes, showing good electrocatalytic performance at low platinum loading (less than 0.05 mg cm-2), while also maintaining long-term stability against coarsening and aggregation of catalytic nanoparticles.

Journal Article↗

Deformation twinning in nanocrystalline aluminum.

We report transmission electron microscope observations that provide evidence of deformation twinning in plastically deformed nanocrystalline aluminum. The presence of these twins is directly related to the nanocrystalline structure, because they are not observed in coarse-grained pure aluminum. We propose a dislocation-based model to explain the preference for deformation twins and stacking faults in nanocrystalline materials. These results underscore a transition from deformation mechanisms controlled by normal slip to those controlled by partial dislocation activity when grain size decreases to tens of nanometers, and they have implications for interpreting the unusual mechanical behavior of nanocrystalline materials.

Journal Article↗

Shock-induced localized amorphization in boron carbide.

High-resolution electron microscope observations of shock-loaded boron carbide have revealed the formation of nanoscale intragranular amorphous bands that occur parallel to specific crystallographic planes and contiguously with apparent cleaved fracture surfaces. This damage mechanism explains the measured, but not previously understood, decrease in the ballistic performance of boron carbide at high impact rates and pressures. The formation of these amorphous bands is also an example of how shock loading can result in the synthesis of novel structures and materials with substantially altered properties.

Journal Article↗

High tensile ductility in a nanostructured metal.

Nanocrystalline metals--with grain sizes of less than 100 nm--have strengths exceeding those of coarse-grained and even alloyed metals, and are thus expected to have many applications. For example, pure nanocrystalline Cu (refs 1-7) has a yield strength in excess of 400 MPa, which is six times higher than that of coarse-grained Cu. But nanocrystalline materials often exhibit low tensile ductility at room temperature, which limits their practical utility. The elongation to failure is typically less than a few per cent; the regime of uniform deformation is even smaller. Here we describe a thermomechanical treatment of Cu that results in a bimodal grain size distribution, with micrometre-sized grains embedded inside a matrix of nanocrystalline and ultrafine (<300 nm) grains. The matrix grains impart high strength, as expected from an extrapolation of the Hall-Petch relationship. Meanwhile, the inhomogeneous microstructure induces strain hardening mechanisms that stabilize the tensile deformation, leading to a high tensile ductility--65% elongation to failure, and 30% uniform elongation. We expect that these results will have implications in the development of tough nanostructured metals for forming operations and high-performance structural applications including microelectromechanical and biomedical systems.

Journal Article↗