Suppression of alpha-tubulin acetylation potentiates therapeutic efficacy of Eribulin in liver cancer.

Hepatocellular carcinoma (HCC) is a prevalent cancer with limited effective treatments. Eribulin mesylate is a novel chemotherapy drug that inhibits microtubule elongation and may impact the tumor microenvironment and immune pathway. This study aims to investigate the impact of changes in microtubule acetylation levels on HCC development and treatment outcomes. Clinical and molecular data were aggregated from databases, with survival analysis conducted to evaluate the relevance of microtubule acetylation. In vitro experiments using HCC cell lines and a tumor cell transplantation model in C57BL/c mice were performed to investigate the effects of microtubule acetylation on Eribulin treatment. A significant correlation was found between the level of lysine 40 acetylation of α-tubulin (acetyl-α-tubulin-lys40) and overall survival of HCC patients, with a better prognosis associated with a lower level of acetyl-α-tubulin-lys40. Knocking down ATAT1 or overexpressing HDAC6 reduced the level of acetyl-α-tubulin-lys40 and sensitized Eribulin treatment both in vitro and in vivo. In summary, acetyl-α-tubulin-lys40 was increased in HCC and was associated with a shorter overall survival of HCC patients. Reducing the level of acetyl-α-tubulin-lys40 can enhance sensitivity to Eribulin treatment both in vitro and in vivo, thereby establishing acetyl-α-tubulin-lys40 as a potential prognostic marker and predictive indicator for Eribulin treatment in HCC patients.

A novel coiled-coil domain containing-related gene signature for predicting prognosis and treatment effect of breast cancer.

PURPOSE: Breast cancer (BRCA) is a prevalent tumor worldwide. The association between the coiled-coil domain-containing (CCDC) protein family and different tumors has been established. However, the prognostic significance of this protein family in breast cancer remains uncertain. METHODS: Gene expression and clinical data were obtained from the TCGA, METABRIC, and GEO databases. Prognosis genes were identified using univariate Cox and LASSO Cox regression, leading to the establishment of a prognostic signature. Subsequently, the risk model was conducted based on survival and clinical feature analyses, and a nomogram for prognosis prediction was developed. Furthermore, analyses of biological function, immune characteristics, and drug sensitivity were performed. Finally, single-cell sequencing data were utilized to uncover the expression patterns of genes in the risk model. RESULTS: Five genes were identified and utilized for risk modeling. The model demonstrated excellent prognostic value as indicated by ROC and Kaplan-Meier analysis. The high-risk group exhibited shorter survival time and higher likelihood of recurrence. Functional annotation indicated a correlation between the risk score and immune pathways. Conversely, the low-risk group displayed a greater enrichment in immune pathways and exhibited more active immune microenvironment characteristics. Additionally, drug sensitivity analysis using both public and our sequencing data revealed that the risk model possessed a broad range of predictive values. CONCLUSIONS: We have developed a gene signature and have verified that patients with low-risk are more likely to have better prognosis and respond positively to therapy. This finding offers a valuable point of reference for BRCA individualized treatment.

Targeting Trop-2 in cancer: Recent research progress and clinical application.

The development of new antitumor drugs depends mainly upon targeting tumor cells precisely. Trophoblast surface antigen 2 (Trop-2) is a type I transmembrane glycoprotein involved in Ca2+ signaling in tumor cells. It is highly expressed in various tumor tissues than in normal tissues and represents a novel and promising molecular target for caner targeted therapy. Up to now, the mechanisms and functions associated with Trop-2 have been extensively studied in a variety of solid tumors. According to these findings, Trop-2 plays an important role in cell proliferation, apoptosis, cell adhesion, epithelial-mesenchymal transition, as well as tumorigenesis and tumor progression. In addition, Trop-2 related drugs are also being developed widely. There are a number of Trop-2 related ADC drugs that have demonstrated potent antitumor activity and are currently been studied, such as Sacituzumab Govitecan (SG) and Datopotamab Deruxtecan (Dato-Dxd). In this study, we reviewed the progress of Trop-2 research in solid tumors. We also sorted out the composition and rationale of Trop-2 related drugs and summarized the related clinical trials. Finally, we discussed the current status of Trop-2 research and expanded our perspectives on its future research directions. Importantly, we found that Trop-2 targeted ADCs have great potential for combination with other antitumor therapies. Trop-2 targeted ADCs can reprogramme tumor microenvironment through multiple signaling pathways, ultimately activating antitumor immunity.

Soil phosphorus drives plant trait variations in a mature subtropical forest.

Earth system models are implementing soil phosphorus dynamic and plant functional traits to predict functional changes in global forests. However, the linkage between soil phosphorus and plant traits lacks empirical evidence, especially in mature forests. Here, we examined the soil phosphorus constraint on plant functional traits in a mature subtropical forest based on observations of 9943 individuals from 90 species in a 5-ha forest dynamic plot and 405 individuals from 15 species in an adjacent 10-year nutrient-addition experiment. We first confirmed a pervasive phosphorus limitation on subtropical tree growth based on leaf N:P ratios. Then, we found that soil phosphorus dominated multidimensional trait variations in the 5-ha forest dynamic plot. Soil phosphorus content explained 44% and 53% of the variance in the traits defining the main functional space across species and communities, respectively. Lastly, we found much stronger phosphorus effects on most plant functional traits than nitrogen at both species and community levels in the 10-year nutrient-addition experiment. This study provides evidence for the consistent pattern of soil phosphorus constraint on plant trait variations between the species and community levels in a mature evergreen broadleaf forest in the East Asian monsoon region. These findings shed light on the predominant role of soil phosphorus on plant functional trait variations in mature subtropical forests, providing new insights for models to incorporate soil phosphorus constraint in predicting future vegetation dynamics.

Enhanced electro-Fenton catalytic performance with in-situ grown Ce/Fe@NPC-GF as self-standing cathode: Fabrication, influence factors and mechanism.

Heterogeneous electro-Fenton (E-F) is considered as an attractive technique for efficient removal of refractory organic pollutants in wastewater. The regeneration of FeII and catalyst reusability are key issues for effective and sustainable degradation. Developing binder-free iron phase/carbon composite cathode is a feasible strategy. In this work, the stable Ce/Fe-nanoporous carbon modified graphite felt electrode (Ce/Fe@NPC-GF) was fabricated using in situ solvothermal method and subsequent carbonization treatment, which worked as the cathode in a heterogeneous electro-Fenton system to degrade sulfamethoxazole. The electrocatalytic activity was significantly improved with doping of Ce. It was found that mesoporous Ce/Fe@NPC-GF cathode demonstrated high oxygen reduction activity and low resistance. The co-existence of FeⅡ/FeⅢ and CeⅢ/CeⅣ redox couples enhanced remarkably interfacial electron transfer, promoting in-situ H2O2 generation and decomposition, sequentially boosting the production of reactive radicals (·OH and ·O2-). Under 20 mA and pH 3, Sulfamethoxazole (SMX) was basically degraded in 120 min, and the removal rate was satisfactory in wide pH (2-6). After 8 cycles, the electrode could still maintain high stability and outstanding catalytic capacity. This work displayed a novel in-situ preparation method of composite cathode with excellent catalytic performance in E-F system, which offered inspiration for developing efficient heterogeneous electro-Fenton cathode material.

Facile construction of highly reactive and stable defective iron-based metal organic frameworks for efficient degradation of Tetrabromobisphenol A via persulfate activation.

Achieving large pore size, high catalytic performance with stable structure is critical for metal-organic frameworks (MOFs) to have more hopeful prospects in catalytic applications. Herein, we had reported a method to synthesize highly reactive yet stable defective iron-based Metal organic frameworks by using different monocarboxylic acids with varying lengths as a modulator. The physical-chemical characterization illustrating that modulators could improve the crystallinity, enlarge pore size and enhance catalytic performance and octanoic acid (OA) was screened to be the suitable choice. The catalytic performance of catalysts was detected through persulfate (PS) activation for degrading Tetrabromobisphenol A (TBBPA). The study demonstrated that the highest degradation efficiency for 0.018 mmol L-1 TBBPA was that 97.79% in the conditions of the 1.0 g L-1 Fe(BDC)(DMF,F)-OA-30 dosage and TBBPA:PS = 200:1. In addition, there was observed that no obvious change of the crystal structure, little the leachable iron concentration in the solutions and no significant loss of catalytic activities of Fe(BDC)(DMF,F)-OA-30 after 5th cycles. The iron valence state of Fe(BDC)(DMF,F)-OA-30 before and after degradation and electrochemical properties reveal that the partial substitution of organic ligands by octanoic acid, when removing OA and forming defects by heat and vacuum treatment to generate coordinatively unsaturated metal sites and accelerate the original transmission of electronic, leading to enhance the activity of persulfate activation for efficient removal TBBPA.