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Oxaliplatin-based chemotherapy is a standard treatment for advanced colorectal cancer (CRC) patients. However, chemoresistance-induced resistance is an essential cause for mortality. Therefore, it is necessary to study the mechanism of drug resistance in CRC.Here, we established two strains of patient-derived organoids (PDOs) selected from oxaliplatin-resistant and treatment-naïve CRC patients. To dissect the drug-resistant mechanisms, these CRC-PDOs were subjected to single-cell RNA sequencing (scRNA-Seq).We found that the drug sensitivity test outcome from these organoids subjected to oxaliplatin and 5-FU exposure was consistent with the clinic readout. CRC-PDOs well recapitulated the morphology and histology of their parental biopsies based on HE and IHC staining of pathological biomarkers. The scRNA-Seq data filtered drug-resistant cell populations and related signaling pathways (e.g. oxidative phosphorylation and ATP metabolic process). The data also revealed several putative drug resistant-driven genes (STMN1, VEGFA and NDRG1) and transcription factors (E2F1, BRCA1, MYBL2, CDX2 and CDX1).We generated an oxaliplatin-resistant CRC organoid model that was employed to provide potential therapeutic targets for treating CRC patients exhibiting oxaliplatin-resistance.

This study investigated the effects of exogenous salicylic acid (SA) treatment (0, control; 3 mmol L

Prenatal life exposure to fine particulate matter (aerodynamic diameter less than or equal to 2.5 µm, PM2.5) has been linked with increased risk of adverse fetal development and birth outcomes in previous studies. However, to our knowledge, no study has investigated the association of maternal PM2.5 with the risk of fetal distress, which is a harmful fetal status and may lead to fetal brain damage, even fetal death. Therefore, we conducted a study to determine the association between maternal PM2.5 and fetal distress among 7835 mother-infant pairs from a birth cohort, in Wuhan, China, 2013–2015. The individual daily PM2.5 level was assessed using land use regression model. We evaluated the association of maternal PM2.5 level over the whole pregnancy with fetal distress by logistic regression model, and estimated the risk between PM2.5 exposure in specific trimester and fetal distress using generalized estimating equations. We observed that per 10 µg/m3 change of maternal PM2.5 level over the whole pregnancy was associated with 25% increased risk of fetal distress (95% confidence interval: 1.09–1.44). Further, we found PM2.5 level in the 2nd trimester, but not in the 1st and 3rd trimesters, was associated with fetal distress. Stratified analyses indicated that the association was only significant among infants who were born in cold seasons. Our study suggested that PM2.5 exposure during the whole pregnancy exhibited significant associations with the risk of fetal distress, and exposure in the 2nd trimester maybe the susceptible window. Further stratified analyses indicated that birth season is a possible modifier in the association.