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Abstract Necroptosis plays a double-edged sword role in necroptotic cancer cell death and tumor immune escape. How cancer orchestrates necroptosis with immune escape and tumor progression remains largely unclear. We found that RIP3, the central activator of necroptosis, was methylated by PRMT1 methyltransferase at the amino acid of RIP3 R486 in human and the conserved amino acid R479 in mouse. The methylation of RIP3 by PRMT1 inhibited the interaction of RIP3 with RIP1 to suppress RIP1-RIP3 necrosome complex, thereby blocking RIP3 phosphorylation and necroptosis activation. Moreover, the methylation-deficiency RIP3 mutant promoted necroptosis, immune escape and colon cancer progression due to increasing tumor infiltrated myeloid-derived immune suppressor cells (MDSC), while PRMT1 reverted the immune escape of RIP3 necroptotic colon cancer. Importantly, we generated a RIP3 R486 di-methylation specific antibody (RIP3ADMA). Clinical patient samples analysis revealed that the protein levels of PRMT1 and RIP3ADMA were positively correlated in cancer tissues and both of them predicted the longer patient survival. Our study provides insights into the molecular mechanism of PRMT1-mediated RIP3 methylation in the regulation of necroptosis and colon cancer immunity, as well as reveals PRMT1 and RIP3ADMA as the valuable prognosis markers of colon cancer.

The lysosome protein RAGA interacts with and promotes lysosome localization and degradation of the macrophage-specific immune checkpoint protein CD47, with possible relevance to lung adenocarcinoma

Catalytic hydrogenation presents a promising approach for converting CO2 into valuable chemicals and fuels, crucial for climate change mitigation. Iron-based catalysts have emerged as key contributors, particularly in driving the reverse water–gas shift and Fischer–Tropsch synthesis reactions. Recent research has focused on enhancing the efficiency and selectivity of these catalysts by incorporating alkali metal promoters or transition metal dopants, enabling precise adjustments to their composition and properties. This review synthesizes recent theoretical advancements in CO2 hydrogenation with iron-based catalysts, employing density functional theory and microkinetic modeling. By elucidating the underlying mechanisms involving metallic iron, iron oxides, and iron carbides, we address current challenges and provide insights for future sustainable CO2 hydrogenation developments.

Okadaic acid (OA), one of marine biotoxins produced by several species of dinoflagellates, can accumulate in marine animals. The consumption of OA-contaminated seafood can cause diarrhoeic shellfish poisoning. Many countries have established regulatory restriction to limit the level of OA in seafood. In the present study, we report a highly sensitive monoclonal antibody (mAb) against OA produced by a new immunogen. Two monoclonal hybridoma cell lines (M8 and M12) that producing mAb with the best sensitivity and specificity were obtained. The obtained mAb-M12 was used to develop an indirect competitive ELISA (icELISA) with 50% inhibition concentrations of 0.15 ng mL−1 and a working range of 0.02–2.74 ng mL−1. The developed icELISA was more sensitive than the previous reports. HPLC-MS confirmed the accuracy and the working range of icELISA, suggesting that the developed icELISA is suitable for the rapid detection of OA in oysters and green mussels.

The extensive utilization of fossil fuels has led to a rapid increase in atmospheric CO2 concentration, resulting in various environmental issues. To reduce reliance on fossil fuels and mitigate CO2 emissions, it is important to explore alternative methods of utilizing CO2 and H2 as raw materials to obtain high-value-added chemicals or fuels. One such method is CO2 methanation, which converts CO2 and H2 into methane (CH4), a valuable fuel and raw material for other chemicals. However, CO2 methanation faces challenges in terms of kinetics and thermodynamics. The reaction rate, CO2 conversion, and CH4 yield need to be improved to make the process more efficient. To overcome these challenges, the development of suitable catalysts is essential. Non-noble metal catalysts have gained significant attention due to their high catalytic activity and relatively low cost. In this paper, the thermodynamics and kinetics of the CO2 methanation reaction are discussed. The focus is primarily on reviewing Ni-based, Co-based, and other commonly used catalysts such as Fe-based. The effects of catalyst supports, preparation methods, and promoters on the catalytic performance of the methanation reaction are highlighted. Additionally, the paper summarizes the impact of reaction conditions such as temperature, pressure, space velocity, and H2/CO2 ratio on the catalyst performance. The mechanism of CO2 methanation is also summarized to provide a comprehensive understanding of the process. The objective of this paper is to deepen the understanding of non-noble metal catalysts in CO2 methanation reactions and provide insights for improving catalyst performance. By addressing the limitations of CO2 methanation and exploring the factors influencing catalyst effectiveness, researchers can develop more efficient and cost-effective catalysts for this reaction.

The excessive consumption of fossil fuels has resulted in massive carbon emissions and serious ecological and environmental crises. Therefore, achieving the efficient utilization of waste carbon sources is considered as an important pathway to addressing the aforementioned issues in the context of carbon neutrality. Developing and designing suitable catalyst materials has become the key to converting COx into valuable platform chemicals and value-added liquid fuels (e.g., CO, CH4, CH3OH, and C2+ hydrocarbons). A moderate interaction between nitrogen-doped carbon materials and active metals is more favorable for the progress of the COx hydrogenation reaction compared to traditional metal oxide carriers. In this work, we comprehensively summarize the synthesis methods of N-doped carbon materials and the relevant research progress in the field of COx hydrogenation. In addition, a general assessment of carbon-based catalysts for COx hydrogenation reactions, concerning the support and metal properties, the activity and product selectivity, and their interactions is systematically discussed. Finally, this review discusses the roles of N-doped carbon materials, the current challenges, and future development directions.

Filopodia, a finger-like structure and actin-rich plasma-membrane protrusion at the leading edge of the cell, has important roles in cell motility. However, the mechanisms of filopodia generation are not well-understood via the actin-related protein 2/3 (ARP2/3) complex in Non-Small Cell Lung Cancer (NSCLC) cells. We previously have demonstrated that PRR11 associates with the ARP2/3 complex to regulate cytoskeleton-nucleoskeleton assembly and chromatin remodeling. In this study, we further demonstrate that PRR11 involves in filopodia formation, focal adhesion turnover and cell motility through ARP2/3 complex. Cell phenotype assays revealed that the silencing of PRR11 increased cellular size and inhibited cell motility in NSCLC cells. Mechanistically, PRR11 recruited and co-localized with Arp2 at the membrane protrusion to promote filopodia formation but not lamellipodia formation. Notably, PRR11 mutant deletion of the proline-rich region 2 (amino acid residues 185–200) abrogated the effect of filopodia formation. In addition, PRR11-depletion inhibited filopodial actin filaments assembly and increased the level of active integrin β1 in the cell surface, whereas reduced the phosphorylation level of focal adhesion kinase (FAKY397) to repress focal adhesion turnover and cell motility in NSCLC cells. Taken together, our findings indicate that PRR11 has critical roles in controlling filopodia formation, focal adhesion turnover and cell motility by recruiting ARP2/3 complex, thus dysregualted expression of PRR11 potentially facilitates tumor metastasis in NSCLC cells.

The malignant environmental changes caused by the ever-increasing amount of anthropogenic CO2 emissions have been particularly prominent in recent years. To achieve carbon mitigation and carbon neutrality, CO2 hydrogenation to methanol is regarded as a promising and sustainable route. However, the development of catalysts with exceptional performance and the establishment of a clear structure–activity relationship remain formidable challenges. Considering the lack of a state-of-the-art review on the catalytic progress of CO2 hydrogenation to methanol over non-noble catalysts, we conducted a detailed review in terms of the thermodynamic analysis, catalytic development, and reaction mechanism. In this work, we mainly reviewed the latest research progress of different catalysts including Cu-based, In2O3-based, bimetallic, solid solution, and other catalysts. Meanwhile, we summarized the effects of the support materials, promoters, and preparation methods on the catalytic performance. In addition, we also summarized the possible reaction mechanisms of direct hydrogenation of CO2 to methanol. Overall, this work would be of importance for the researchers to obtain a comprehensive understanding of the design and development of efficient catalysts for CO2 hydrogenation to methanol.

Background: rRNA-derived small RNAs (rsRNAs) represent a novel class of small non-coding RNAs (sncRNAs), produced by the specific cleavage of rRNAs; however, their roles in tumor development are unclear. In the present study, we explored the effect of a kind of rsRNA-28S, which originates from 28S rRNA, on the chemoresistance of prostate cancer cells and the mechanisms underlying its effect. Methods: Quantitative reverse transcription PCR (RT-PCR) was performed to quantify rsRNA-28S levels in serum samples taken from prostate cancer patients. DU-145R cells, which are resistant to both paclitaxel and docetaxel, were generated from parental DU-145 cells. Northern blot was conducted to detect cellular rsRNA-28S levels following drug treatments. To verify the effect of rsRNAs-28S on chemoresistance, antisense oligonucleotides were utilized to block rsRNA-28S functions, and a series of assays were further performed, such as cell viability, cell proliferation, colony formation and tumor sphere formation. The target gene of rsRNA-28S was explored using dual-luciferase reporter gene assay. Results: The rsRNA-28S level was reduced in the serum samples of patients who received chemotherapy compared to that of patients who did not. Furthermore, the rsRNA-28S level was remarkably declined in DU-145R cells, and drug treatments decreased the levels of rsRNA-28S in DU-145 and DU-145R cells. Moreover, rsRNA-28S inhibition enhanced the chemoresistance of prostate cancer cells as well as their cancer stem cell characteristics. Mechanistically, the prostaglandin I2 synthase (PTGIS) gene transcript was verified as a target of rsRNA-28S, as rsRNA-28S inhibited the translation of PTGIS mRNA by directly binding the 3′ untranslated region of PTGIS mRNA. rsRNA-28S inhibition was also found to increase PTGIS abundance, and PTGIS overexpression significantly enhanced prostate cancer cell chemoresistance. Conclusions: Our findings indicate that rsRNA-28S attenuates prostate cancer cell chemoresistance by downregulating its target gene PTGIS. This study not only greatly contributes to systematic identification and functional elucidation of chemoresistance relevant rsRNAs, but also promotes rsRNA-included combinatorial therapeutic regimens for cancer.

Cervical cancer is one of the most common gynecological malignancies with poor prognosis due to constant chemoresistance and repeated relapse. Ciclopirox olamine (CPX), a synthetic antifungal agent, has recently been identified to be a promising anti-cancer candidate. However, the detailed mechanisms related to its anti-cancer effects remain unclear and need to be further elucidated. In this study, we found that CPX could induce proliferation inhibition in cervical cancer cells by targeting PARK7. Further results demonstrated that CPX could induce cytoprotective autophagy by downregulating the expression of PARK7 to activate PRKAA1 or by PARK7-independent accumulation of ROS to inhibit mTOR signaling. Meanwhile, CPX treatment increased the glycogen clustering and glycophagy in cervical cancer cells. The presence of N-acetyl-l-cysteine (NAC), a ROS scavenger, led to further clustering of glycogen in cells by reducing autophagy and enhancing glycophagy, which promoted CPX-induced inhibition of cervical cancer cell proliferation. Together, our study provides new insights into the molecular mechanisms of CPX in the anti-cancer therapy and opens new avenues for the glycophagy in cancer therapeutics.

Hepatocellular carcinoma is one of the most common fatal malignancies worldwide. Thus far, the hepatocellular carcinoma prognosis has been bleak due to deficiencies in the identification and diagnosis of early hepatocellular carcinoma. Ciclopirox olamine (CPX) is a synthetic antifungal agent and has been considered as an anti-cancer candidate drug recently, though the detailed mechanisms related to its anti-cancer effect in hepatocellular carcinoma have not yet been revealed. Here, we found that CPX could inhibit proliferation in HCC cells but not in intrahepatic cholangiocarcinoma cells by arresting the cell cycle. Moreover, the anti-cancer effects of CPX in HCC cells were also attributed to CPX-triggered ROS accumulation and DJ-1 downregulation. Additionally, CPX could promote complete autophagic flux, which alleviated the anti-cancer effect of CPX in HCC cells, whereas the ROS scavenger (NAC) would attenuate CPX-induced protective autophagy. Interestingly, CPX could also induce glycogen clustering in HCC cells. Altogether, this study provides a new insight into the detailed molecular mechanisms of CPX as an anti-cancer therapy and a strategy for treating hepatocellular carcinoma.

Hydrogenation of CO2 to value-added chemicals and fuels not only effectively alleviates climate change but also reduces over-dependence on fossil fuels. Therefore, much attention has been paid to the chemical conversion of CO2 to value-added products, such as liquid fuels and aromatics. Recently, efficient catalysts have been developed to face the challenge of the chemical inertness of CO2 and the difficulty of C–C coupling. Considering the lack of a detailed summary on hydrogenation of CO2 to liquid fuels and aromatics via the Fischer–Tropsch synthesis (FTS) route, we conducted a comprehensive and systematic review of the research progress on the development of efficient catalysts for hydrogenation of CO2 to liquid fuels and aromatics. In this work, we summarized the factors influencing the catalytic activity and stability of various catalysts, the strategies for optimizing catalytic performance and product distribution, the effects of reaction conditions on catalytic performance, and possible reaction mechanisms for CO2 hydrogenation via the FTS route. Furthermore, we also provided an overview of the challenges and opportunities for future research associated with hydrogenation of CO2 to liquid fuels and aromatics.

BackgroundThe prognostic stratification of colon cancer using only the tumor-node-metastasis (TNM) stage has some limitations. We sought to increase the accuracy of stratifying patients with stage III colon cancer by constructing a prognostic model combining carcinoembryonic antigen (CEA) with TNM.MethodsWe retrospectively analyzed the data generated from stage III colon cancer patients who had early postoperative CEA measurement from 21 to 100 days after surgery from 2006 to 2017. CEA value was processed using restricted cubic splines (RCS) method. The prognostic model was developed using cox proportional hazards regression.ResultsThe time later than 20 days after surgery was optimal for measuring CEA, which was determined by comparing the prognostic value for preoperative and postoperative CEA (N = 2,049), and by evaluating the relationship between the hazard ratio (HR) and postoperative CEA measuring time. Postoperative CEA, T stage and N stage were selected into the final model, and the mean integrated-AUC (iAUC) was 0.78 with 1,000 × bootstrap resampling, which was higher than the model using only T and N stages (TN model; mean iAUC, 0.66). The net reclassification improvement (NRI) was 15% when compared with TN model. Patients could be divided into high and low risk groups by the model, and 3-year disease-free survival (DFS) were 53.7% and 87.0%, respectively (HR, 4.30; 95% CI, 2.65 to 6.96; P < 0.001). Similar results were found in the validation set.ConclusionsStage III colon cancer could be stratified more accurately using the new prognostic model combining postoperative CEA with T and N stage.

BackgroundIncreasing evidence indicates that inflammation and nutritional status are associated with survival outcomes in patients with colorectal cancer (CRC). This study aimed to investigate the prognostic values of preoperative inflammatory and nutritional factors and develop a prognostic model individually predicting overall survival (OS) and disease-free survival (DFS) in patients with CRC.MethodsWe retrospectively collected data on patients with CRC who underwent radical surgery. Independent prognostic inflammatory and nutritional markers were identified and novel prognostic models were developed incorporating the identified factors. The discriminative ability and model-fitting performance were evaluated by receiver operating characteristic curves and Akaike information criteria. Clinical usefulness was assessed by decision curve analysis.ResultsA total of 400 eligible patients were identified. Multivariate analysis identified pN stage, tumor differentiation grade, neutrophil count, and body mass index as independent prognostic factors for OS, and pN stage, tumor differentiation grade, neutrophil count, neutrophil-lymphocyte ratio, and serum albumin as prognostic factors for DFS. The combined inflammatory and nutritional prognostic model showed better discriminative ability, model-fitting performance, and net benefits than the inflammatory and nutritional models alone, and the American Joint Committee on Cancer (AJCC) 8th TNM classification for predicting OS and DFS.ConclusionPreoperative nutritional and inflammatory factors have significant prognostic value in patients with CRC. A novel prognostic model incorporating preoperative inflammatory and nutritional markers provides better prognostic performance than the AJCC 8th TNM classification. A novel nomogram incorporating preoperative inflammatory and nutritional markers can individually predict OS and DFS in patients with CRC.

Tumor metastasis is the main contributor to high recurrence and mortality in colorectal cancer (CRC). In a previous study, we found that DJ-1 plays an important role in CRC metastasis, and is the main target in Ciclopirox olamine (CPX)-treated CRC. However, the mechanism underlying DJ-1-induced CRC metastasis remains elusive. In the present study, our results showed that DJ-1 could activate Wnt signaling resulting in enhanced invasive potential and epithelial-to-mesenchymal transition (EMT) in CRC cells. RNA-seq and bioinformatics analysis reveals that the DJ-1/Wnt signaling pathway may promote CRC cells’ EMT by regulating fibroblast growth factor 9 (FGF9) expression. Molecular validation showed that expression of FGF9 was upregulated by the DJ-1/Wnt signaling pathway and decreasing FGF9-expression impeded DJ-1-induced CRC invasive ability and EMT, suggesting that FGF9 is involved in DJ-1-enhanced CRC metastasis. In addition, we show that FGF9 was overexpressed in CRC human specimens and was significantly associated with tumor differentiation. High FGF9 expression was correlated with worse overall survival, and a correlation exhibited between FGF9 and EMT markers (E-cadherin and Vimentin) in CRC samples. Together, our results determined that FGF9 was involved in DJ-1-induced invasion and EMT in CRC cells, and may represent a promising therapeutic candidate for CRC anti-metastatic strategies.

Our previous studies have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene and implicates in regulating the proliferation in lung cancer. However, its precise role in cell cycle progression remains unclear. Our recent evidences show that PRR11 silencing has an effect on autophagy in non-small-cell lung cancer (NSCLC) cells. Two human NSCLC cell lines, H1299 and A549 were transiently transfected with against PRR11 siRNA. The Cell Counting Kit-8 and plate clone formation assay showed that downregulation of PRR11 inhibited the cell proliferation associated with cell cycle related genes reduced. And our data suggested that PRR11 depletion expression enhanced the autophagosomes formation, followed with downregulation of P62 and upregulation of LC3-II protein. Furthermore, the immunoblotting results indicated that silencing of PRR11 inactivated the Akt/mTOR signaling pathway. Collectively, these results demonstrated PRR11 had an effective role in autophagy in NSCLC cells through Akt/mTOR autophagy signaling pathways. Therefore, it is helpful to clarify the function of PRR11 in tumorigenesis of NSCLC. Keywords: Akt/mTOR, Autophagy, Cell proliferation, Non-small-cell lung cancer, PRR11

BackgroundPRR14 (Proline rich protein 14) was firstly identified for its ability to specify and localize heterochromatin during cell cycle progression. Aberrant expression of PRR14 is associated with the tumorigenesis and progression of lung cancer. However, its involvement in colon cancer remains unknown. Herein, we report the role of PRR14 in colon cancer.MethodsColon cancer tissue microarray was used to analyze and compare the expression of PRR14 among some clinicopathological characteristics of colon cancer. HCT116 and RKO cells were transfected with siRNA to downregulate PRR14 expression. The roles of PRR14 in proliferation, migration and invasion of the cell lines were determined using cell counting kit-8, colony formation assay, wound healing assay and transwell assays respectively. The expression of PRR14 was measured using immunofluorescence, qRT- PCR and western blot. Epithelial-mesenchymal transition (EMT) markers were determined by western blot.ResultsPRR14 was highly expressed in colon cancer tissues, and the expression level was correlated with tumor size, distant metastasis and Tumor Node Metastasis stages. Functional study revealed that downregulation of PRR14 inhibited colon cancer cells growth, migration and invasion. Furthermore, knockdown of PRR14 inhibited epithelial-mesenchymal transition (EMT) process, cell cycle-associated proteins expression and p-AKT level.ConclusionPRR14 may promote the progression and metastasis of colon cancer, and may be a novel prognostic and therapeutic marker for the disease.

Silk gland cells undergo multiple endomitotic cell cycles during silkworm larval ontogeny. Our previous study demonstrated that feeding is required for continued endomitosis in the silk gland cells of silkworm larvae. Furthermore, the insulin signaling pathway is closely related to nutritional signals. To investigate whether the insulin signaling pathway is involved in endomitosis in silk gland cells, in this study, we initially analyzed the effects of bovine insulin on DNA synthesis in endomitotic silk gland cells using 5-bromo-2'-deoxyuridine (BrdU) labeling technology, and found that bovine insulin can stimulate DNA synthesis. Insulin signal transduction is mainly mediated via phosphoinositide 3-kinase (PI3K)/Akt, the target of rapamycin (TOR) and the extracellular signal-regulated kinase (ERK) pathways in vertebrates. We ascertained that these three pathways are involved in DNA synthesis in endomitotic silk gland cells using specific inhibitors against each pathway. Moreover, we investigated whether these three pathways are involved in insulin-stimulated DNA synthesis in endomitotic silk gland cells, and found that the PI3K/Akt and TOR pathways, but not the ERK pathway, are involved in this process. These results provide an important theoretical foundation for the further investigations of the mechanism underlying efficient endomitosis in silk gland cells.

Extractive distillation has great significance for the separation of ethylbenzene from C8 aromatic hydrocarbons. Herein, a distillation process for the separation of ethylbenzene was designed using methyl phenylacetate as an extractant. A genetic algorithm (GA) was used to evaluate the economic and environmental factors of the process, and Aspen Dynamic was used to assess the dynamic performance. The sequential optimization method was used to obtain the initial process parameters. Then, the total annual cost and CO2 emissions were minimized by NSGA-III to increase the economic and environmental benefits. To enhance the search performance of GA, the mutation probability and crossover probability were studied and adjusted. The optimal total annual cost and CO2 emissions were 11.7% and 23.7% lower than those of the initial process. Based on a steady process, two control strategies, which were the flow rate of the recycling solvent controlled by entrainer makeup flow rate (CS1) and the bottom flow rate of the extractant recovery column (CS2), were designed. The results showed that the temperature deviation of CS2 was smaller than that of CS1, and the temperature of the process was more stable under the control of CS2. [ABSTRACT FROM AUTHOR]