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Background and Aim Methods Results Conclusions Hepatocellular carcinoma (HCC) emerges as a formidable malignancy marked by elevated morbidity and mortality rates, coupled with a dismal prognosis. The revelation of gene–protein associations has presented an avenue for the exploration of novel therapeutic targets.Pooling plasma proteomic data (seven published GWAS) and HCC data (DeCODE cohort), we applied MR to identify potential drug targets, which were further validated in the FinnGen cohort and UK Biobank. Subsequent colocalization and summary‐data‐based Mendelian randomization analyses were performed for potential associations of this set of proteins. In addition, enrichment information pathways were investigated in depth by KEGG pathway analysis, single‐cell sequencing, PPI and DGIdb, ChEMBL, and DrugBank database analyses, specific cell types enriched for expression were identified, interacting proteins were identified, and finally, druggability was assessed.In summary, the levels of 10 proteins are linked to HCC risk. Elevated levels of TFPI2 as well as decreased levels of ALDH1A1, KRT18, ADAMTS13, TIMD4, SCLY, HRSP12, TNFAIP6, FTCD, and DDC are associated with increased HCC risk. Notably, HRSP12 show the strongest evidence. These genes are primarily expressed in specific cell types within the HCC TME. Moreover, intricate protein–protein interactions, involving key players like ALDH1A1 and RIDA, ALDH1A1 and DDC, and ALDH1A1 and KRT18, contribute significantly to the amino acid metabolism and dopaminergic neurogenesis pathway. Proteins such as ALDH1A1, KRT18, TFPI2, and DDC are promising targets for HCC therapy and broader cancer drug development. Targeting these proteins offers substantial potential in advancing HCC treatment strategies.This research delineates 10 protein biomarkers linked to HCC risk and offers novel perspectives on its etiology, as well as promising avenues for the screening of HCC protein markers and therapeutic agents. [ABSTRACT FROM AUTHOR]

The signal transducer and activator of transcription (STAT) is a family of intracellular cytoplasmic transcription factors involved in many biological functions in mammalian signal transduction. Among them, STAT3 is involved in cell proliferation, differentiation, apoptosis, and inflammatory responses. Despite the advances in the treatment of pancreatic cancer in the past decade, the prognosis for patients with pancreatic cancer remains poor. STAT3 has been shown to play a pro-cancer role in a variety of cancers, and inhibitors of STAT3 are used in pre-clinical and clinical studies. We reviewed the relationship between STAT3 and pancreatic cancer and the latest results on the use of STAT3 inhibitors in pancreatic cancer, with the aim of providing insights and ideas around STAT3 inhibitors for a new generation of chemotherapeutic modalities for pancreatic cancer. [ABSTRACT FROM AUTHOR]

The decomposition of sodium zincate, NaZn(OH) 3 , in the alkaline solution (Na 2 O–ZnO–H 2 O equilibrium system) containing 30–34% Na 2 O is complex because of the temperature dependence of the solid precipitate which occurred. In this paper, the sodium zincate decomposition in the alkali solution containing 32.43% Na 2 O and 22.93% ZnO is investigated by assessing the effects of temperature, dilution factor and time on the decomposition rate ( R ) of NaZn(OH) 3 . The results show that ZnO precipitates when the saturated NaZn(OH) 3 solution at 100 °C is subjected to water dilution and subsequent cooling to 75, 50 and 25 °C. The decomposition kinetics at 75 °C can be described by the equation, R = 1 − e − 1.1 t 0.3 , where t is the reaction time. ZnO crystal obtained is rod-shaped and becomes coarser at higher temperatures and lower dilution times. The decomposition rate of NaZn(OH) 3 increases with dilution temperature, stirring time and dilution factors. Sodium zincate decomposition and recycling of alkaline solution can be illustrated using the Na 2 O–ZnO–H 2 O equilibrium phase diagram, which are similar to those in alumina production. The results are beneficial to the extraction of zinc from its oxide ores leached with alkaline solution. [ABSTRACT FROM AUTHOR]

As a component of the innate immune system, there is emerging evidence to suggest that neutrophils may play a critical role in the initiation and progression of hepatocellular carcinoma (HCC). Neutrophil extracellular traps (NETs) are web-like chromatin structures that protrude from the membranes during neutrophil activation. Recent research has shown that NETs, which are at the forefront of the renewed interest in neutrophil studies, are increasingly intertwined with HCC. By exploring the mechanisms of NETs in HCC, we aim to improve our understanding of the role of NETs and gain deeper insights into neutrophil biology. Therefore, this article provides a summary of key findings and discusses the emerging field of NETs in HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Fan, Dong, Li, Chen and Zhou.)

Introduction: The involvement of endoplasmic reticulum (ER) stress in cancer biology is increasingly recognized, yet its role in pancreatic cancer (PC) remains unclear. This study aims to elucidate the impact of ER stress on prognosis and biological characteristics in PC patients. Methods: A bioinformatic analysis was conducted using RNA-seq data and clinicopathological information from PC patients in the TCGA and ICGC databases. The ER stress-associated gene sets were extracted from MSigDB. ER stress-associated genes closely linked with overall survival (OS) of PC patients were identified via log-rank test and univariate Cox analysis, and further narrowed by LASSO method. A risk signature associated with ER stress was formulated using multivariate Cox regression and assessed through Kaplan-Meier curves, receiver operating characteristic (ROC) analyses, and Harrell's concordance index. External validation was performed with the ICGC cohort. The single-sample gene-set enrichment analysis (ssGSEA) algorithm appraised the immune cell infiltration landscape. Results: Worse OS in PC patients with high-risk signature score was observed. Multivariate analysis underscored our ER stress-associated signature as a valuable and independent predictor of prognosis. Importantly, these results based on TCGA were further validated in ICGC dataset. In addition, our risk signature was closely associated with homeostasis, protein secretion, and immune regulation in PC patients. In particular, PC microenvironment in the high-risk cluster exhibited a more immunosuppressive status. At last, we established a nomogram model by incorporating the risk signature and clinicopathological parameters, which behaves better in predicting prognosis of PC patients. Discussion: This comprehensive molecular analysis presents a new predictive model for the prognosis of PC patients, highlighting ER stress as a potential therapeutic target. Besides, the findings indicate that ER stress can have effect modulating PC immune responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Xu, Xu, Zhang, Li, Xu, Zhu, Li, Liang and Zhou.)