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Background: Fruquintinib is a third-line and subsequent targeted therapy for patients with metastatic colorectal cancer (mCRC). Identifying survival predictors after fruquintinib is crucial for optimizing the clinical use of this medication. Objectives: We aimed to identify factors influencing the prognosis of patients with mCRC treated with fruquintinib and to leverage these insights to develop a nomogram model for estimating survival rates in this patient population. Design: Multicenter retrospective observational study. Methods: We collected patient data from January 2019 to October 2023, with one healthcare institution's data serving as the training cohort and the other three hospitals' data serving as the multicenter validation cohort. The nomogram for overall survival was calculated from Cox regression models, and variable selection was screened using the univariate Cox regression analysis with additional variables based on clinical experience. Model performance was measured by the concordance index (C-index), calibration curves, decision curve analyses (DCA), and utility (patient stratification into low-risk vs high-risk groups). Results: Data were ultimately collected on 240 patients, with 144 patients included in the training cohort and 96 included in the multicenter validation cohort. Predictors included in the nomogram were CA199, body mass index, T stage, the primary site of the tumor, and other metastatic and pathological differentiation. The C-index of the nomogram in the training set and multicenter validation was 0.714 and 0.729, respectively. The models were fully calibrated and their predictions aligned closely with the observed data. DCA curves indicated the promising clinical benefits of the predictive model. Finally, the reliability of the model was also verified through the risk classification using the nomogram. Conclusions: We constructed a nomogram for mCRC treated with fruquintinib based on six variables that may be used to assist in personalizing the use of the drug. Plain language summary: A nomogram for predicting OS after application of fruquintinib in patients with mCRC The prognostic predictors of fruquintinib as a third-line and subsequent treatment agent for patients with mCRC have not been established. In this study, we explored possible factors influencing its prognosis and developed a nomogram model for estimating survival rates in this patient population. The nomogram, based on six key variables including CA199, BMI, T stage, primary tumor site, other metastatic sites, and pathological differentiation, was validated through a rigorous multicenter validation process. The nomogram has the potential to help clinicians personalize the use of fruquintinib for mCRC patients. [ABSTRACT FROM AUTHOR]

Solar-driven photo-thermal catalytic CO2 methanation reaction is a promising technology to alleviate the problems posed by greenhouse gases emissions. However, designing advanced photo-thermal catalysts remains a research challenge for CO2 methanation reaction. In this work, a series of ABO3 (A = lanthanide, B = transition metal) perovskite catalysts with Ce-substituted LaNiO3 (La1−xCexNiO3, x = 0, 0.2, 0.5, 0.8, 1) were synthesized for CO2 methanation. The La0.2Ce0.8NiO3 exhibited the highest CH4 formation rate of 258.9 mmol·g−1·hcat−1, CO2 conversion of 55.4% and 97.2% CH4 selectivity at 300 °C with the light intensity of 2.9 W·cm−2. Then the catalysts were thoroughly analyzed by physicochemical structure and optical properties characterizations. The partial substitution of the A-site provided more active sites for the adsorption and activation of CO2/H2. The sources of the active sites were considered to be the oxygen vacancies (Ov) created by lattice distortions due to different species of ions (La3+, Ce4+, Ce3+) and exsolved Ni0 by H2 reduction. The catalysts have excellent light absorption absorbance and low electron–hole (e−/h+) recombination rate, which greatly contribute to the excellent performance in photo-thermal synergistic catalysis (PTC) CO2 methanation. The results of in situ irradiated electron paramagnetic resonance spectrometer (ISI-EPR) and ISI-X-ray photoelectron spectroscopy (XPS) indicated that the aggregation of unpaired electrons near the defects and Ni metal (from La and Ce ions to Ov and Ni0) accelerated adsorption and activation of CO2/H2. At last, the catalyst properties and structure were correlated with the proposed reaction mechanism from the in situ diffuse reflection infrared Fourier transform spectrum (DRIFTS) measurements. The in situ precipitation of the B-site enhanced the dispersion of Ni, while its enriched photoelectrons upon illumination further promote hydrogen dissociation. More H* spillover accelerated the rate-determining step (RDS) of HCOO* hydrogenation. This work provides the theoretical basis for the development of catalysts and industrial application. [ABSTRACT FROM AUTHOR]

Background: This study aims to compare the effectiveness and safety of the combination of raltitrexed, S‐1 (RS), and fruquintinib with the combination of RS and bevacizumab in patients with refractory metastatic colorectal cancer (mCRC). Methods: This retrospective cohort included mCRC patients who received the RS plus fruquintinib or regorafenib as the third‐line therapy from May 2019 to April 2023. A propensity score matching (PSM) analysis was used to balance the baseline characteristics of all patients. Overall survival (OS), progression‐free survival (PFS), tumor response, and safety of the two regimens were evaluated. Results: Of the 153 patients enrolled, 123 patients received the RS plus bevacizumab and 30 patients received the RS plus fruquintinib. After PSM, 30 pairs were analyzed. Patients treated with RS plus fruquintinib had a longer PFS than those treated with RS plus bevacizumab before PSM (5.0 months vs. 4.3 months, p = 0.008) and after PSM (5.0 months vs. 4.4 months, p = 0.012). A longer OS was also observed in RS plus fruquintinib group before PSM and after PSM, but there was no statistic difference between two groups after PSM. Both objective response rate and disease control rate were higher in the RS plus fruquintinib cohort than those in the RS plus bevacizumab cohort before PSM, and the difference in values between the two groups reduced after PSM. The adverse effects (AEs) of both groups were well tolerated. Conclusion: In patients with refractory mCRC, RS plus fruquintinib demonstrated a superior OS, PFS than RS plus bevacizumab and had manageable AEs. [ABSTRACT FROM AUTHOR]

Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner‐type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single‐cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A+ umbrella cells and a simultaneous increase in progenitor‐like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A+ umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A+ umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A+ umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A+ umbrella cells in HIC urothelium. Finally, we conducted in vitro and in vivo experiments to confirm the potential of the TLR3–NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self‐repair strategies for HIC patients. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Aims In this study, the control effects of synthetic microbial communities composed of peanut seed bacteria against seed aflatoxin contamination caused by Aspergillus flavus and root rot by Fusarium oxysporum were evaluated. Methods and results Potentially conserved microbial synthetic communities (C), growth-promoting synthetic communities (S), and combined synthetic communities (CS) of peanut seeds were constructed after 16S rRNA Illumina sequencing, strain isolation, and measurement of plant growth promotion indicators. Three synthetic communities showed resistance to root rot and CS had the best effect after inoculating into peanut seedlings. This was achieved by increased defense enzyme activity and activated salicylic acid (SA)-related, systematically induced resistance in peanuts. In addition, CS also inhibited the reproduction of A. flavus on peanut seeds and the production of aflatoxin. These effects are related to bacterial degradation of toxins and destruction of mycelia. Conclusions Inoculation with a synthetic community composed of seed bacteria can help host peanuts resist the invasion of seeds by A. flavus and seedlings by F. oxysporum and promote the growth of peanut seedlings. [ABSTRACT FROM AUTHOR]