Biology subjects

chen, y.

Publications and source records attributed to chen, y..

8 recordsLinked to original sources

bioRxiv2026

KRAS-driven metabolic reprogramming of enhanced MFSD2A-mediated lysophosphatidylcholine scavenging promotes survival and progression of pancreatic ductal adenocarcinoma

Oncogenic KRAS drives lipid reprogramming in pancreatic ductal adenocarcinoma (PDAC) to promote disease progression, and these changes are manifest in circulation. Using mass spectrometry, we performed lipidomic analyses on plasmas from a cohort of 93 newly-diagnosed resectable PDAC cases, 43 patients with chronic pancreatitis, and 93 age- and sex-matched healthy controls, the results of which revealed pronounced reductions in circulating lysophosphatidylcholines (LysoPC) as a prominent feature associated with PDAC. Using stable-isotope resolved lipidomics, we further found that PDAC cells exhibit a lipid scavenging phenotype characterized by preferential uptake of extracellular unsaturated LysoPCs to sustain pro-growth signals. Restricting bioavailability of extracellular unsaturated LysoPCs shifted the metabolic phenotype of PDAC cells towards enhanced de novo lipogenesis and autophagy, which was accompanied by suppression of AKT signaling activities and increased susceptibility to apoptosis. Using bulk, single-cell, and spatial transcriptomic datasets together with functional experiments, we identified oncogenic KRAS-mediated upregulation of major facilitator superfamily domain-containing protein 2a (MFSD2A) as a key mediator that facilitates extracellular uptake of LysoPCs in PDAC cells. Loss of MFSD2A expression mimicked LysoPC restriction and resulted in inhibition of AKT signaling and increased propensity of PDAC cells to undergo apoptosis in vitro and suppressed tumor growth in vivo. Therapeutic targeting of the KRAS-MFSD2A-LysoPC axis via repurposing of the synthetic alkyl-lysophospholipid edelfosine promoted potent anti-cancer effects in vitro that were mechanistically attributed to reduced extracellular uptake of LysoPCs, and attenuation of AKT signaling. Collectively, our findings describe a previously unrecognized onco-metabolic program of enhanced LysoPC scavenging mediated by MFSD2A that promotes PDAC progression and that is therapeutically targetable via repurposing edelfosine.

cancer biology↗

bioRxiv2026

AART enables fast and accurate cross-platform proteomic translation

Plasma proteomic profiling has been widely used for biomarker discovery, disease prediction and diagnosis, and patient stratification. However, technical differences across assay platforms often result in low-to-moderate agreement, limiting study reproducibility, data integration, and model transferability. Here we present AART, a cross-platform proteomic translation framework that integrates matched-protein ridge regression with proteome-wide residual learning. We benchmarked AART spanning three independent cohorts profiled using three major platforms, including Olink, SomaScan, and mass spectrometry. Across all six translation directions, AART achieved the best performance compared with baseline methods for both overlapping and non-overlapping protein translations, with a relative improvement of 92.0% on average over direct mapping and by up to 31.6% over cpiVAE, the strongest baseline. Proteins that were accurately translated and improved by AART were enriched for extracellular, vesicle-associated, and tissue-restricted plasma biology. In downstream applications, AART improved the reproducibility of proteomic association analyses relative to direct cross-platform comparison by 75.5% for type 2 diabetes and 370.6% for Alzheimers disease. AART-enabled cohort integration enhanced diagnostic accuracy for amyotrophic lateral sclerosis by 92.6% compared with non-integration analysis. AART was overall one to three orders of magnitude faster than cpiVAE, facilitating biobank-scale applications. Together, these results establish AART as a fast, accurate, and scalable framework for cross-platform proteomic translation, enabling more reproducible, transferable, and integrated proteomic research.

bioinformatics↗

bioRxiv2026

A Phospho-Switch for Cell Fate Control

Cell fate control is thought to be complex, likely involving both cell intrinsic and extrinsic factors, and remains ill-defined at the molecular level. Here we show a phospho-switch controls cell fate both in vitro and in vivo. We first show that SALL4 is phosphorylated at multiple sites, but only T903 as the primary one as SALL4T903A lost BAF interaction and [~]90% activity in reprogramming. Mechanistically, we demonstrate that SALL4pT903 is sensitive to BMP4 signaling through DUSP9 axis. Finally, we show by tetraploid embryo complementation that mESCs harboring SALL4T903A can sustain embryo development but with severe defects including cranial hypoplasia and flattened skull vault after birth. A genome wide search identifies 608 transcription factors harboring the same HTG motif sandwiched by two zinc fingers, suggesting that this phospho-switch may be a conserved mechanism to control cell fate. In briefA phosphorylation switch, pT903, in SALL4 governs cell fate by modulating BAF complex interaction in response to BMP4-DUSP9 signaling, as its dephosphorylation abrogates reprogramming and causes cranial defects in mice, suggesting that such switches may broadly regulate cell fate machinery. HighlightsO_LIA T903 phospho-switch in SALL4 gates BAF interaction to orchestrate gene activation and reprogramming C_LIO_LIBMP4-DUSP9 signaling converges on SALL4pT903 dephosphorylation to couple extracellular cues with cell fate determination C_LIO_LIDisrupting the SALL4-T903 phospho-switch causes severe postnatal developmental defects in mice. C_LIO_LIThe HTGE motif may function as a central switch on key transcription factors for sensing upstream signals C_LI

developmental biology↗

bioRxiv2025

Identification of pyroptosis-related diagnostic model relate to immune infiltration in osteoarthritis

BackgroundOsteoarthritis (OA) is a common chronic diseases which were associated with aging and progressive joint dysfunction. Pyroptosis, a novel mode of cell death. The effect of pyroptosis on osteoarthritis (OA) progression is still in the exploratory stage, and the specific mechanism is unclear. MethodsOA data sets were obtained from the GEO databases website. Bioinformatics analysis was conducted to identify pyroptosis-related genes (PRGs), construct a pyroptosis-related diagnostic model, and identify subtypes. We established the random forest (RF) model as well as a nomogram of differentially expressed PRGs. The association between immunity and pyroptosis was comprehensively explored. Finally, the expression levels of 3 OA characteristic genes were verified by qRT-PCR and immunohistochemistry. ResultsSeven differentially expressed PRGs (CASP3, GPX4, NOD1, TIRAP, SCAF11, CASP4, and CASP9) were obtained by differential analysis to establish RF models, and three important OA genes (CASP9, TIRAP, and SCAF11) were obtained. ROC curve proved that the established model had high diagnostic accuracy. Based on the above three important PRGs, a high-precision nomogram model is constructed. Two PRG models are determined by consensus clustering method. The enrichment degree of immune cells in cluster A was higher than that in cluster B, suggesting that cluster A might be related to the occurrence and development of OA. GPX4 was found to be positively correlated with higher immune infiltration. Finally, the expression levels of 3 OA characteristic genes were verified by qRT-PCR and immunohistochemistry. ConclusionWe constructed an effective prognostic model according to PRGs in OA and integrated explored the association between pyroptosis and immunity-related elements. This article provides a strong point for investigating directed immunotherapy methods with novelty for OA.

immunology↗

bioRxiv2023

EGFR inhibition in lung adenocarcinoma upregulates cell surface expression of the placental antigen ALPP and enhances efficacy of ALPP-ADC therapy

Alkaline phosphatase placental type (ALPP) and ALPPL2 are closely related and regulated GPI anchored proteins that are known to be expressed on the cell surface in some cancers, whereas normal tissue expression is largely limited to the placenta. Clinical utility of ALPP is potentially limited by heterogenous expression in tumors. Here, we assessed ALPP and ALPPL2 surfaceome protein levels in 158 cancer cell lines and mRNA expression levels in 10,967 tumors representing 32 cancer types from The Cancer Genome Atlas (TCGA), which revealed ALPP, and to a lesser extent ALPPL2, to be variably expressed in several cancer types including lung adenocarcinoma (LUAD). Surface expression of ALPP was confirmed by tissue microarray analysis of 204 lung tumors. Using LUAD as a model system, we demonstrated that treatment with EGFR inhibitors, or induction of cancer cell quiescence via nutrient deprivation greatly enhanced ALPP surface expression. Mechanistic studies revealed that enhancement of surface ALPP expression in LUAD following gefitinib treatment was mediated through repression of EGFR signaling and activation of the transcription factor FoxO3a, which was identified as an upstream transcriptional regulator of ALPP. Using xenograft models of LUAD, we further demonstrated that gefitinib treatment upregulates surface expression of ALPP in LUAD cells but not in normal tissues. Combination therapy with gefitinib and an ALPP antibody conjugated with Monomethylauristatin F (ALPP-ADC-MAF) resulted in superior anti-cancer efficacy compared with gefitinib or ALPP-ADC-MAF alone. Our findings support a novel combination treatment modality that boosts the efficacy of ALPP-ADC directed therapy.

cancer biology↗

bioRxiv2022

Tegaserod maleate suppresses the growth of gastric cancer in vivo and in vitro by targeting MEK1/2

Gastric cancer (GC), ranking fifth in global incidence and fourth in mortality. The current treatments for GC include surgery, chemotherapy, and radiotherapy. Although management and treatment strategies for GC have been improved over the last decade, the overall five-year survival rate remains less than 30%. Therefore, there is an urgent need to find novel therapeutic or preventive strategies that can increase GC patient survival rates. In the current study, we found that tegaserod maleate, a FDA-approved drug, could inhibit the proliferation of gastric cancer cells. Tegaserod maleate binds to MEK1 /2 and inhibits MEK1 /2 kinase activity. Moreover, the construction of CRISPER/Cas9 cell line further verified that tegaserod maleate depended on MEK1 /2 to inhibit the progress of gastric cancer. Notably, we found that tegaserod maleate suppressed tumor growth in patient-derived gastric xenograft (PDX) mouse model. We also compared tegaserod maleate with trametinib, a clinical MEK1/2 inhibitor, and comfirmed that tegaserod maleate have the same effect in inhibiting tumor volume and tumor weight. Our findings suggest that tegaserod maleate can inhibit GC proliferation by targeting MEK1/2.

pathology↗

bioRxiv2021

Vibrio cholerae may be transmitted to humans from bullfrog through food or water

Bullfrog is one of the most important economic aquatic animals in China. It is widely cultured in southern China, and is a key breed recommended as an industry of poverty alleviation in China. During recent years, a fatal bacterial disease has often been found in cultured bullfrogs. The clinical manifestations of the diseased bullfrogs were severe intestinal inflammation and even anal prolapse. A bacterial pathogen was isolated from the diseased bullfrog intestines. The bacterium was identified as Vibrio cholerae using morphological, biochemical and 16S rRNA phylogenetic analysis. In this study, V. cholerae was isolated and identified from diseased bullfrogs for the first time, providing a basis for the diagnosis and control of the disease. At the same time, it was also found that V. cholerae may be transmitted to humans from bullfrogs through bullfrog food and aquaculture water, creating a serious threat for human health. Therefore, society should pay attention to the modes of transmission of Vibrio cholerae from bullfrog and formulate reasonable safety measures to avoid disasters.

pathology↗

bioRxiv2018

How green are residential areas? An analysis of community greening emerging multi-source geo-data

Urban residential greening provides opportunities for social integration and physical exercise. These activities are beneficial to promoting citizens mental health, relieving stress and reducing obesity and violent crimes. However, how to measure the distribution and spatial difference of green resources in urban residential areas have been controversial. This study takes the greening of urban residential units in Shenzhen City as its research object, measures the various greening index values of each residential unit, and analyses the spatial distribution characteristics of residential greening, regional differences and influencing factors. Large sample of street view pictures, urban land use and high-resolution remote sensing image data are employed to establish an urban residential greening database containing 14,196 residential units. This study proposes three greening indicators, namely, green coverage index, green view index, and accessible public green land index, for measuring the green coverage of residential units, the visible greening of surrounding street space and the public green land around, respectively. Results show that (1) the greening level of residential units in Shenzhen City is generally high, with the three indicators averaging 32.7%, 30.5% and 15.1%, respectively; (2) the types of residential greening differ per area; and (3) the level of residential greening is affected by development intensity, location, elevation and residential type. Such findings can serve as a reference for improving the greening level of residential units. This study proposes an accessible public green land index as a measure for the spatial relationship between residential units and surrounding green spaces. It suggest that future green space planning should pay more attention to the spatial distribution of public green land, and introduce quantitative indicators to ensure sufficient public green lands around the walking range of residential areas.

ecology↗