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Xiaolong Zhang

Publications and source records attributed to Xiaolong Zhang.

10 recordsLinked to original sources
PubMed2026

Multi-omics identification and functional validation of signal regulatory protein gamma as a prognostic biomarker and immune regulator in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) comprises biologically diverse tumors, and durable responses to immune-checkpoint blockade are achieved by only a subset of patients. There remains a need for markers that connect clinical outcome with malignant-cell phenotypes and tissue-level immune organization. METHODS: We integrated The Cancer Genome Atlas HNSCC cohort (TCGA-HNSC), five Gene Expression Omnibus (GEO) validation cohorts, single-cell RNA sequencing, Visium spatial transcriptomics, cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq)-informed protein-potential inference, pharmacogenomic screening, genetic-risk analysis and experimental validation. A reconstructed 296-pipeline survival modelling framework was used to prioritize prognostic hub genes across validation-cohort-specific analyses. RESULTS: SIRPG was repeatedly ranked among the top ten selected genes in all five validation cohorts. At single-cell resolution, SIRPG-high tumor cells showed stronger malignant-cell features, immune-inhibitory and metabolic programs, Scissor-positive risk association, CLCA2/P53-related perturbation signals and inferred SIRPG-CD47/signal regulatory protein (SIRP) communication. Spatial analyses placed this axis within an immune-checkpoint-coupled niche, supported by Maxspin/multiview intercellular spatial modelling (MISTy) spatial coupling, communication analysis by optimal transport (COMMOT)-inferred CD47-SIRPG communication and scProTrans-inferred CD47/SIRPG protein-potential overlap. Functionally, SIRPG knockdown reduced HNSCC cell viability and increased apoptosis, whereas re-expression of short hairpin RNA (shRNA)-resistant SIRPG restored the CLCA2-BAX/BCL2 protein response. CONCLUSION: Together, these findings identify SIRPG as an immune-related prognostic hub and context-dependent tumor-cell regulator associated with apoptosis, immune communication and spatial microenvironmental organization in HNSCC.

Humans↗
PubMed2025

The GSA Family in 2025: A Broadened Sharing Platform for Multi-omics and Multimodal Data.

The Genome Sequence Archive family (GSA family) provides a comprehensive suite of database resources for archiving, retrieving, and sharing multi-omics data for the global academic and industrial communities. It currently comprises four distinct database members: the Genome Sequence Archive (GSA, https://ngdc.cncb.ac.cn/gsa), the Genome Sequence Archive for Human (GSA-Human, https://ngdc.cncb.ac.cn/gsa-human), the Open Archive for Miscellaneous Data (OMIX, https://ngdc.cncb.ac.cn/omix), and the Open Biomedical Imaging Archive (OBIA, https://ngdc.cncb.ac.cn/obia). Compared to its 2021 version, the GSA family has expanded significantly by introducing a new repository, the OBIA, and by comprehensively upgrading the existing databases. Notable enhancements to the existing members include broadening the range of accepted data types, strengthening quality control systems, improving the data retrieval system, and refining data-sharing management mechanisms.

Humans↗
PubMed2006

Dendritic cell surface calreticulin is a receptor for NY-ESO-1: direct interactions between tumor-associated antigen and the innate immune system.

How the immune system recognizes endogenously arising tumors and elicits adaptive immune responses against nonmutated tumor-associated Ags is poorly understood. In search of intrinsic factors contributing to the immunogenicity of the tumor-associated Ag NY-ESO-1, we found that the NY-ESO-1 protein binds to the surface of immature dendritic cells (DC), macrophages, and monocytes, but not to that of B cells or T cells. Using immunoprecipitation coupled with tandem mass spectrometry, we isolated DC surface calreticulin as the receptor for NY-ESO-1. Calreticulin Abs blocked NY-ESO-1 binding on immature DC and its cross-presentation to CD8+ T cells in vitro. Calreticulin/NY-ESO-1 interactions provide a direct link between NY-ESO-1, the innate immune system, and, potentially, the adaptive immune response against NY-ESO-1.

Antigens, Neoplasm↗
PubMed2004

TULA: an SH3- and UBA-containing protein that binds to c-Cbl and ubiquitin.

Downregulation of protein tyrosine kinases is a major function of the multidomain protein c-Cbl. This effect of c-Cbl is critical for both negative regulation of normal physiological stimuli and suppression of cellular transformation. In spite of the apparent importance of these effects of c-Cbl, their own regulation is poorly understood. To search for possible novel regulators of c-Cbl, we purified a number of c-Cbl-associated proteins by affinity chromatography and identified them by mass spectrometry. Among them, we identified the UBA- and SH3-containing protein T-cell Ubiquitin LigAnd (TULA), which can also bind to ubiquitin. Functional studies in a model system based on co-expression of TULA, c-Cbl, and EGF receptor in 293T cells demonstrate that TULA is capable of inhibiting c-Cbl-mediated downregulation of EGF receptor. Furthermore, modulation of TULA concentration in Jurkat T-lymphoblastoid cells demonstrates that TULA upregulates the activity of both Zap kinase and NF-AT transcription factor. Therefore, our study indicates that TULA counters the inhibitory effect of c-Cbl on protein tyrosine kinases and, thus, may be involved in the regulation of biological effects of c-Cbl. Finally, our results suggest that TULA-mediated inhibition of the effects of c-Cbl on protein tyrosine kinases is caused by TULA-induced ubiquitylation and degradation of c-Cbl.

Amino Acid Substitution↗
PubMed2002

Serine 577 is phosphorylated and negatively affects the tRNA binding and eIF2alpha kinase activities of GCN2.

Protein kinase GCN2 regulates translation initiation by phosphorylating eukaryotic initiation factor 2alpha (eIF2alpha), impeding general protein synthesis but specifically inducing translation of GCN4, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. GCN2 activity is stimulated in amino acid-deprived cells through binding of uncharged tRNA to a domain related to histidyl tRNA synthetase. We show that GCN2 is phosphorylated by another kinase on serine 577, located N-terminal to the kinase domain. Mutation of Ser-577 to alanine produced partial activation of GCN2 in nonstarved cells, increasing the level of phosphorylated eIF2alpha, derepressing GCN4 expression, and elevating the cellular levels of tryptophan and histidine. The Ala-577 mutation also increased the tRNA binding affinity of purified GCN2, which can account for the elevated kinase activity of GCN2-S577A in nonstarved cells where uncharged tRNA levels are low. Whereas Ser-577 remains phosphorylated in amino acid-starved cells, its dephosphorylation could mediate GCN2 activation in other stress or starvation conditions by lowering the threshold of uncharged tRNA required to activate the protein.

Mass Spectrometry↗
PubMed2002

N-Terminal peptide labeling strategy for incorporation of isotopic tags: a method for the determination of site-specific absolute phosphorylation stoichiometry.

Determining the phosphorylation stoichiometry at specific sites in a phosphoprotein is a very challenging task. We describe here a novel mass spectrometry based method that is capable of measuring the absolute phosphorylation stoichiometry at specific sites without the need for specific internal standards, phospho-site antibodies or radioactivity. The method is based on a gentle chemical labeling strategy which specifically and differentially labels the N-terminus of all peptides in a sample with either a D(5)- or D(0)-propionyl group and measures the ratio of the abundance of the D(5)/D(0) peptide pairs simultaneously using mass spectrometry. Using matrix-assisted laser desorption/ionization (MALDI), the method can measure absolute stoichiometry to within at least 10% and can be applied to both in vitro and in vivo phosphorylated peptides and proteins. Furthermore, this method can potentially be applied to the quantitative study of other types of protein post-translational modifications, and the profiling of protein expression on the proteome level.

Amino Acid Sequence↗
PubMed2002

Serine phosphorylation of Stat5 proteins in lymphocytes stimulated with IL-2.

Tyrosine phosphorylation regulates cytokine-induced dimerization of STAT proteins. Serine phosphorylation has also been found to occur in a number of STAT proteins, including Stat1, Sat3, Stat4, Stat5a, Stat5b and Stat6, and was shown to be important for maximal transcriptional activation mediated by Stat1, Stat3 and Stat4, but not for Stat5a or Stat5b. As these latter proteins were studied in transiently transfected COS-7 cells stimulated with prolactin, we sought to further investigate the significance of their serine phosphorylation in a more physiologically based system in response to IL-2. Both Stat5a and Stat5b were rapidly phosphorylated on serine in response to IL-2 and the phosphorylation site in Stat5a was mapped to Ser780, which is not conserved in Stat5b. In vitro studies with reporter constructs, and experiments in which wild-type and mutant Stat5a retroviruses were used to transduce Stat5a-deficient splenocytes revealed that the serine mutant constructs were not diminished in their ability to mediate IL-2 signaling and if anything exhibited augmented proliferative capability. Thus, in contrast to the apparent importance of serine phosphorylation for transcriptional activation by Stat1, Stat3 and Stat4 in response to IFN, IL-6 and IL-12 respectively, serine phosphorylation of Stat5a does not enhance Stat5a-mediated signaling in response to IL-2.

Animals↗
PubMed2002

[Computer aided intracranial aneurysm embolization with GDC].

OBJECTIVE: To establish an expert system that automatically generates optimal GDC selection program for the embolization of intracranial aneurysm. METHODS: Twenty highly cost-effective cases of intracranial aneurysm embolized with GDC dense packing were collected. Each of them contains information including aneurysm's volume measured by three-dimension digital subtraction angiography (3D DSA), aneurysm's location, maximum transverse diameter, maximum length diameter, and GDC selection program. An expert system made up of a case base, a mathematical model simulating experts' experience (established with the help of data mining techniques combining multi-layer perceptron network with polyhedrons in high dimensional space), and data envelopment analysis (DEA), was implemented. RESULTS: When the user inputted four required parameters (volume, location, maximum transverse diameter, and maximum length diameter) into the expert system and clicked the "program design" button, candidate GDC selection program(s) would be presented in the result box. CONCLUSION: Case base, data mining techniques, and DEA can be used to establish the expert system that automatically generates optimal GDC selection program for the embolization of intracranial aneurysm. Its clinical value needs to be further evaluated.

Adult↗
PubMed2002

[Three dimensional digital subtraction angiography in volume embolization ratio measurement of densely packing experimental aneurysms].

OBJECTIVE: To calculate the volume embolization ratio of densely packing experimental aneurysms by three dimensional digital subtraction angiography (3D-DSA). METHODS: Six experimental crotch aneurysms were created microsurgically in the common carotid artery of white rabbits. Two weeks later, each aneurysm's volume was measured with 3D-DSA surface shaded display(SSD) and the correction of lacteprene balloon calibration method. In the same time, the aneurysms were densely packed with electric detachable coils. The volume of coils that were used in each aneurysm was calculated separately. The ratio of coils volume and aneurysm volume was the volume embolization ratio (VER). RESULTS: The aneurysms volumes measured by 3D DSA SSD ranged from 0.037 to 0.087 ml. The VER ranged from 23.5% to 32.5% (average 27.4%). CONCLUSION: The minimum VER of densely packing experimental crotch aneurysms with electronic detachable coils was 23.5%.

Angiography, Digital Subtraction↗