PubMed Health⌕ Search

Biomedical subjects

Xiaodong Yan

Publications and source records attributed to Xiaodong Yan.

12 recordsLinked to original sources

Integrated single-cell and bulk transcriptomic analysis identifies a novel senescent fibroblast subtype associated with poor prognosis in acral melanoma.

BACKGROUND: Acral melanoma (AM) exhibits significant intratumoral heterogeneity, but its tumor microenvironment (TME) and immune regulation remain unclear. This study aims to dissect TME heterogeneity and establish a prognostic model based on key cell subpopulations. METHODS: We collected AM single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). Unsupervised clustering, CellChat, and Scissor analysis were performed to characterize cellular heterogeneity, cell-cell communication, and prognosis-related cell subpopulations. Kaplan-Meier analysis was used to assess the prognostic value of key genes, which were further validated by multiplex immunohistochemistry (mIHC). RESULTS: In AM, Mel_C2, C7, and C9 with high SEMA6A and KIT expression were strongly linked to poor prognosis. We further identified a senescent fibroblast subpopulation (sCAF_CDKN2A) characterized by high fibroblast senescence signature (FSS) scores. Integrating Scissor analysis of fibroblast subtypes with bulk prognostic data, we identified COL3A1, VCAN, and KIT as prognosis-associated genes upregulated in poor-outcome-related fibroblast subsets. Cell-cell communication analysis revealed that sCAF_CDKN2A engages in an immunosuppressive network, interacting with regulatory T cells (Tregs) via MIF signaling and receiving signals from exhausted CD8+ T cells through PPIA-BSG interactions. Using transcription factor expression patterns from these fibroblast subtypes, we constructed a prognostic model that effectively stratified patients into distinct risk groups with significant differences in overall survival (OS). mIHC confirmed significantly higher protein levels of SEMA6A and COL3A1 in tumor tissues compared to matched normal tissues. CONCLUSIONS: We established a novel prognostic model for AM and identified sCAF_CDKN2A as an immunosuppressive senescent fibroblast subpopulation driving poor prognosis.

Acral melanoma↗

Surface stress changes induced by the conformational change of proteins.

A potential binding assay based on conformational-change-induced micromechanical motion is described. Calmodulin was used to modify a microcantilever (MCL) by a self-assembled layer-by-layer approach. The results showed that the modified MCL bent when the proteins changed their conformation upon binding with Ca2+. The cantilever deflection amplitudes were different under different ionic strengths, indicating different degrees of conformational change of the proteins in these conditions. On the contrary, cantilevers modified by proteins, such as hemoglobin and myoglobin, that do not change conformations upon binding with analytes do not cause the cantilever deflection. These results suggest that the conformational changes of proteins may be used to develop cantilever biosensors, and the MCL system has potential for use in label-free, protein-analyte screening applications.

Animals↗

AUTO3DEM--an automated and high throughput program for image reconstruction of icosahedral particles.

AUTO3DEM is an automation system designed to accelerate the computationally intensive process of three-dimensional structure determination from images of vitrified icosahedral virus particles. With minimal user input and intervention, AUTO3DEM manages the flow of data between the major image reconstruction programs, monitors the progress of the computations, and intelligently updates the input parameters as the resolution of the model is improved. It is designed to be used on any computer running the Linux or UNIX operating systems and can be run in parallel mode on multi-processor systems.

Algorithms↗

Ab initio random model method facilitates 3D reconstruction of icosahedral particles.

Model-based, three-dimensional (3D) image reconstruction procedures require a starting model to initiate data analysis. We have designed an ab initio method, which we call the random model (RM) method, that automatically generates models to initiate structural analysis of icosahedral viruses imaged by cryo-electron microscopy. The robustness of the RM procedure was demonstrated on experimental sets of images for five representative viruses. The RM method also provides a straightforward way to generate unbiased starting models to derive independent 3D reconstructions and obtain a more reliable assessment of resolution. The fundamental scheme embodied in the RM method should be relatively easy to integrate into other icosahedral software packages.

Algorithms↗

Microcantilevers modified by horseradish peroxidase intercalated nano-assembly for hydrogen peroxide detection.

Detection of hydrogen peroxide is of industry interest and of biological importance. Here we report a new approach to hydrogen peroxide measurement using multilayer modified microcantilevers. Through a layer-by-layer nanoassembly technique, horseradish peroxidase was intercalated into a nanoscale multilayer assembly on one surface of microcantilevers. These enzyme-functionalized microcantilevers deflected in response to hydrogen peroxide concentrations in the nanomolar level. The magnitudes of bending were proportional to the concentrations of hydrogen peroxide. Furthermore, our study also showed that microcantilever technique may be used as a novel, more sensitive tool for the study of the conformational or structural changes of enzymes or proteins on surfaces.

Adsorption↗

A model-based parallel origin and orientation refinement algorithm for cryoTEM and its application to the study of virus structures.

We present a model-based parallel algorithm for origin and orientation refinement for 3D reconstruction in cryoTEM. The algorithm is based upon the Projection Theorem of the Fourier Transform. Rather than projecting the current 3D model and searching for the best match between an experimental view and the calculated projections, the algorithm computes the Discrete Fourier Transform (DFT) of each projection and searches for the central section ("cut") of the 3D DFT that best matches the DFT of the projection. Factors that affect the efficiency of a parallel program are first reviewed and then the performance and limitations of the proposed algorithm are discussed. The parallel program that implements this algorithm, called PO(2)R, has been used for the refinement of several virus structures, including those of the 500 Angstroms diameter dengue virus (to 9.5 Angstroms resolution), the 850 Angstroms mammalian reovirus (to better than 7A), and the 1800 Angstroms paramecium bursaria chlorella virus (to 15 Angstroms).

Algorithms↗

Glucose oxidase multilayer modified microcantilevers for glucose measurement.

We report a novel enzyme-based microcantilever sensor by using layer-by-layer nanoassembly modification. A glucose oxidase (GOx) functionalized microcantilever underwent bending when it was exposed to glucose solutions. The magnitudes of bending were proportional to the concentrations of glucose. The cantilever bending was specific toward glucose, but not to other sugars such as mannose, fructose, or galactose. The flow rate effect on the cantilever bending response is also discussed. The bending mechanism was investigated, and the kinetic and thermodynamic analysis and experimental results showed that the conformational change of GOx and gluconic formation were the origin of cantilever deflection.

Enzymes, Immobilized↗

Experimental and theoretical aspects of glucose measurement using a microcantilever modified by enzyme-containing polyacrylamide.

We report a glucose oxidase-containing polyacrylamide hydrogel-coated microcantilever sensor for the measurement of glucose. This enzymatic reaction of glucose results in swelling of the hydrogel due to formation of charged ions (gluconate molecules and protons). The microcantilever undergoes reversible and reproducible bending deflection upon exposure to solutions containing various glucose concentrations due to swelling or shrinking of the hydrogels. The microcantilever deflections increase when the glucose concentrations increase. A theoretical model has been built to correlate volume changes of the gel with microcantilever bending. The calculated data matched with the experimental results very well. Such hydrogel-coated microcantilevers could potentially be used to prepare microcantilever-based chemical and biological sensors when other enzymes are immobilized in the hydrogel.

Acrylic Resins↗

The marine algal virus PpV01 has an icosahedral capsid with T=219 quasisymmetry.

Phaeocystis pouchetii virus (PpV01) infects and lyses the haptophyte Phaeocystis pouchetii (Hariot) Lagerheim and was first isolated from Norwegian coastal waters. We have used electron cryomicroscopy and three-dimensional image reconstruction methods to examine the native morphology of PpV01 at a resolution of 3 nm. The icosahedral capsid of PpV01 has a maximum diameter of 220 nm and is composed of 2,192 capsomers arranged with T=219 quasisymmetry. One specific capsomer in each asymmetric unit contains a fiber-like protrusion. Density attributed to the presence of a lipid membrane appears just below (inside) the capsid. PpV01 is the largest icosahedral virus whose capsid structure has been determined in three dimensions from images of vitrified samples. Striking similarities in the structures of PpV01 and a number of other large double-stranded DNA viruses are consistent with a growing body of evidence that they share a common evolutionary origin.

Capsid↗

The Asian nitrogen cycle case study.

We analyzed nitrogen budgets at national and regional levels on a timeline from 1961-2030 using a model, IAP-N 1.0. The model was designed based upon the Inter-governmental Panel on Climate Change (IPCC) methods using Asia-specific parameters and a Food and Agriculture Organization of the United Nations (FAO) database. In this paper we discuss new reactive-nitrogen and its various fates, and environmental nitrogen enrichment and its driving forces. The anthropogenic reactive nitrogen of Asia dramatically increased from approximately 14.4 Tg N yr-1 in 1961 to approximately 67.7 Tg N yr-1 in 2000 and is likely to be 105.3 Tg N yr-1 by 2030. Most of the anthropogenic reactive-nitrogen has accumulated in the environment. We found that an increasing demand for food and energy supplies and the lack of effective measures to improve the efficiency of fertilizer nitrogen use, as well as effective measures for the prevention of NOx emissions from fossil-fuel combustion, are the principal drivers behind the environmental nitrogen-enrichment problem. This problem may be finally solved by substituting synthetic nitrogen fertilizers with new high-efficiency nitrogen sources, but solutions are dependent on advances in biological technology.

Asia↗