Biomedical subjects

Chang Xu

Publications and source records attributed to Chang Xu.

4 recordsLinked to original sources

PubMed2026

P1D6 inhibits FnBP-induced extracellular proteome remodeling: proteomic evidence for a novel intervention strategy in atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory skin disorder characterized by skin barrier impairment, chronic inflammation, and intense pruritus. Staphylococcus aureus (S. aureus) critically contributes to its pathogenesis; however, the mechanistic role of its virulence factor fibronectin-binding protein (FnBP) in keratinocytes remains poorly understood. This study used bibliometric analysis and quantitative proteomics to examine the relationship. We first performed a bibliometric analysis, revealing a sustained increase in publications on S. aureus and AD, peaking at 99 articles in 2023, with hotspots focused on skin barrier function, immune inflammation, and pediatrics. Quantitative proteomics was employed to investigate how FnBP reshapes the extracellular proteome and whether the anti-α5 integrin antibody P1D6 exerts interventional effects. HaCaT cells were stimulated with recombinant FnBP alone or in combination with P1D6, followed by data-independent acquisition (DIA)-based proteomic analysis of secretome changes. Proteomic analysis identified FnBP-induced differentially expressed proteins enriched in immune- and barrier-related pathways, including cell adhesion, cell junctions, and VEGFA-VEGFR2 signaling. P1D6 intervention significantly inhibited the secretome profile and identified 241 core responsive proteins, of which approximately 52% returned to baseline levels after intervention (P > 0.05). These proteins were primarily enriched in pathways governing protein homeostasis, folding, proteasomal degradation, and interleukin-7 signaling. Notably, P1D6 modulated the downregulation of ATP5F1B and P4HB, key effectors within the interleukin-7 pathway. This study demonstrates that FnBP remodels the keratinocyte secretome by disrupting protein homeostasis, consequently inducing barrier injury and chronic inflammation related to AD, which can be effectively blocked by P1D6. Combined with bibliometric trends and proteomic evidence, this study focuses on FnBP, an underexplored virulence factor, and provides novel insights into AD pathogenesis and therapeutic interventions.

Humans↗

PubMed2026

Divergent responses of the gill, hepatopancreas, and eyestalk to acute alkalinity stress in Penaeus vannamei: Osmoregulatory compromise, metabolic trade-off, and endocrine disruption.

The expansion of aquaculture into inland saline-alkali waters is constrained by high carbonate alkalinity (CA), a severe environmental stressor for crustaceans. However, the systemic molecular mechanisms underlying its lethal toxicity remain poorly understood. In this study, we employed a comparative transcriptomic approach to investigate the tissue-specific responses of Pacific white shrimp, Penaeus vannamei, under acute lethal stress (48 h-LC50). We focused on three functionally distinct organs: the gill, hepatopancreas, and eyestalk. The results revealed a systemic but highly tissue-specific transcriptomic response. The gill, as the primary interface, exhibited severe structural impairment and critical failure of osmoregulation, highlighted by the significant downregulation of delta-1-pyrroline-5-carboxylate synthetase (P5CS). In contrast, the hepatopancreas initiates a profound metabolic trade-off, sacrificing growth-related pathways to bolster a robust antioxidant defense system, as evidenced by the activation of sulfur metabolism and high protein turnover. The eyestalk displayed a striking disconnect between hyperactivated stress signaling pathways (e.g., mTOR/FoxO) and the collapse of its protein secretory machinery, marked by the suppression of the ER translocon component Sec61. Collectively, our findings suggest that lethal alkalinity toxicity in P. vannamei results from systemic collapse driven by a complex interplay of osmoregulatory failure, metabolic trade-offs, and endocrine disruption. This study provides a comprehensive molecular snapshot of an organism at its physiological limit, offering novel insights into the adaptive strategies and ultimate tolerance boundaries of crustaceans in extreme environments.

Animals↗

PubMed2026

Calibrated Prediction Intervals for Polygenic Scores: Updated Comparisons, Contextual Calibration, and Data Normalization.

Calibrated prediction intervals for polygenic scores (PGS) are essential for communicating individual-level uncertainty in genomic medicine. We present updated comparisons of two methods for constructing such intervals: CalPred, a parametric approach, and PredInterval, a non-parametric approach. Our results show that both methods can achieve calibrated coverage, although CalPred additionally requires a sufficiently large calibration set. The two methods also exhibit complementary trade-offs with respect to dataset size and risk identification. We further show that contextual calibration, as introduced in Hou et al. and followed in Shi et al., is most naturally achieved through appropriate phenotype normalization and data preprocessing. Apparent miscalibration can arise from inadequate normalization or from providing contextual information to some methods but not others. In UK Biobank, standard GWAS phenotype normalization procedures are sufficient to achieve contextual calibration for traits analyzed. In the extreme simulations of Hou et al. and Shi et al., supplying contextual covariates to PredInterval restores contextual calibration without normalization, and appropriate normalization can achieve contextual calibration without supplying covariates, while also substantially improving upstream tasks including association power and PGS accuracy. Together, these results underscore the central role of phenotype normalization and data preprocessing in GWAS analyses, including reliable uncertainty quantification for PGS.

Journal Article↗

PubMed2021

Evaluating the analytical validity of circulating tumor DNA sequencing assays for precision oncology.

Circulating tumor DNA (ctDNA) sequencing is being rapidly adopted in precision oncology, but the accuracy, sensitivity and reproducibility of ctDNA assays is poorly understood. Here we report the findings of a multi-site, cross-platform evaluation of the analytical performance of five industry-leading ctDNA assays. We evaluated each stage of the ctDNA sequencing workflow with simulations, synthetic DNA spike-in experiments and proficiency testing on standardized, cell-line-derived reference samples. Above 0.5% variant allele frequency, ctDNA mutations were detected with high sensitivity, precision and reproducibility by all five assays, whereas, below this limit, detection became unreliable and varied widely between assays, especially when input material was limited. Missed mutations (false negatives) were more common than erroneous candidates (false positives), indicating that the reliable sampling of rare ctDNA fragments is the key challenge for ctDNA assays. This comprehensive evaluation of the analytical performance of ctDNA assays serves to inform best practice guidelines and provides a resource for precision oncology.

Circulating Tumor DNA↗