Identification and validation of the role of ZNF281 in 5-fluorouracil chemotherapy of gastric cancer.

BACKGROUND: The early diagnosis of gastric cancer (GC) and overcoming chemotherapy resistance is challenging. The aberrant expression of zinc finger protein 281 (ZNF281) and the over-activation of the Wnt/ß-catenin pathway are oncogenic factors and confer tumor chemoresistance. ZNF281 modulates the Wnt/ß-catenin pathway to influence malignant tumor behavior. However, the role of ZNF281 in GC chemotherapy and the relationship with the Wnt/ß-catenin pathway have not been elucidated by researchers. METHODS: We explored differences in ZNF281 expression in Pan-cancer and normal tissues, the effect of its expression on prognosis of patients treated with 5-fluorouracil (5-FU). Cox regression was utilized to determine whether ZNF281 is an independent prognostic factor. Enrichment analysis was performed to explore the mechanism underlying ZNF281's role in 5-FU treatment. We assessed the relationship between ZNF281 and the tumour microenvironment (TME) and combined bulk-RNA and single-cell RNA data to analyse the relationship between ZNF281 and immune infiltration. In vitro experiments verified the effects of ZNF281 knockdown on proliferation, invasion, migration, apoptosis, DNA damage of GC cells with 5-FU treated and the Wnt/ß-catenin pathway proteins. RESULTS: ZNF281 was highly expressed in seven cancers and correlates with the prognosis. It is an independent prognostic factor in 5-FU treatment. ZNF281 correlates with TME score, CD8T cell abundance. ZNF281 is primarily associated with DNA repair and the Wnt/ß-catenin pathway. ZNF281 knockdown enhanced the effect of 5-FU on phenotypes of GC cells. CONCLUSION: We identified and verified ZNF281 as one of the potential influencing factors of 5-FU treatment in GC and may be associated with the Wnt/ß-catenin pathway. Low ZNF281 may contribute to improved 5-FU sensitivity in GC patients.

Multi-omics analysis reveals hepatic lipid metabolism profiles and serum lipid biomarkers upon indoor relevant VOC exposure.

As a widespread indoor air pollutant, volatile organic compound (VOC) caused various adverse health effects, especial the damage to liver, which has become a growing public concern. However, the current toxic data are intrinsically restricted in the single or major VOC species. Limited knowledge is available regarding toxic effects, biomarkers and underlying mechanisms of real indoor VOC-caused liver damage. Herein, an indoor relevant VOC exposure model was established to evaluate the hepatic adverse outcomes. Machine learning and multi-omics approaches, including liver lipidomic, serum lipidomic and liver transcriptomic, were utilized to uncover the characteristics of liver damage, serum lipid biomarkers, and involved mechanism stimulated by VOC exposure. The result showed that indoor relevant VOC led to the abnormal hepatic lipid metabolism, mainly manifested as a decrease in triacylglycerol (TG) and its precursor substance diacylglycerol (DG), which could be contributed to the occurrence of hepatic adverse outcomes. In terms of serum lipid biomarkers, five lipid biomarkers in serum were uncovered using machine learning to reflect the hepatic lipid disorders induced by VOC. Multi-omics approaches revealed that the upregulated Dgkq disturbed the interconversion of DG and phosphatidic acid (PA), leading to a TG downregulation. The in-depth analysis revealed that VOC down-regulated FoxO transcription factor, contributing to the upregulation of Dgkq. Hence, this study can provide valuable insights into the understanding of liver damage caused by indoor relevant VOC exposure model VOC exposure, from the perspective of multi-omics analysis.

Optimization of the emergency endoscopy process for patients with esophagogastric variceal bleeding using failure mode and effect analysis.

OBJECTIVE: To optimize the emergency endoscopy process for patients with esophagogastric variceal bleeding (EGVB) using failure mode and effect analysis (FMEA). METHOD: In this retrospective analysis, we enrolled patients who were hospitalized in Ganzhou People's Hospital from January 2021 to December 2021. They were divided into 51 cases before and 51 cases after the intervention according to the time of FMEA model intervention. The risk of unsafe transport, endoscopic hemostasis success rate, RPN (risk priority number) value, dual venous access time, resuscitation success rate, emergency endoscopy timeout execution rate, patient health education awareness rate, and endoscopic ligation of esophageal varices (EVL) procedure volume were compared accordingly before and after the procedure. RESULTS: After the FMEA intervention, the emergency endoscopy process for EGVB patients was optimized, the risk of unsafe transport for emergency EGVB endoscopy was reduced, and the success rate of emergency endoscopic hemostasis for patients was improved. Also, the failure mode of RPN values greater than 12 was improved. After the countermeasures were implemented, the resuscitation success rate of EGVB patients reached 95%, the safe transport pass rate increased from 88% to 98.7%, and the patient health education awareness increased from 69% to 92%. The number of EGVB patients who underwent EVL surgery ranked second in the province. The waiting time, gastric function recovery time, dual venous access time, and hospital stay of patients who underwent the optimized procedure were significantly shorter compared to those before implementation (all P<0.01). The incidence of adverse events was significantly lower in patients who underwent the optimized procedure compared to the pre-implementation period (P<0.01). CONCLUSION: Applying FMEA to analyze and optimize the process of EGVB patients undergoing emergency endoscopy can maximize patient life safety and treatment safety, as well as improve medical quality and care safety.

Synthetic Study Aiming at the Tricyclic Core of 12-epi-JBIR-23/24.

The synthetic study toward highly enantio- and diastereoselective synthesis of the tricyclic framework of 12-epi-JBIR-23/24, a natural product analogue showing inhibitory activity against four malignant pleural mesothelioma cell lines, is presented herein. In this synthesis, a rhodium-catalyzed asymmetric three-component Michael/aldol reaction introduces three consecutive tertiary carbon centers, while the unique epoxyquinol core motif is successfully forged via [3,3]-sigmatropic rearrangement of an allylic xanthate, vinylogous Pummerer rearrangement, and a selective mesylation/epoxidation cascade of a triol.

Naturally occurring [4 + 2] type terpenoid dimers: sources, bioactivities and total syntheses.

Covering: up to January 2020[4 + 2] type terpenoid dimers are natural products biosynthetically derived from [4 + 2] cycloaddition between two terpenoid monomers. They have attracted the attention of scientists due to their complex architectures, biological activities, natural production pathways and synthetic challenges. In this review article, we highlight recent research progress on naturally occurring [4 + 2] type terpenoid dimers, including their sources, bioactivities, biosynthetic hypotheses and total chemical syntheses.

Construction of BCDEF Core of Andilesin C.

A synthetic study toward the BCDEF core skeleton of andilesin C is presented. Key elements involved iron-promoted intramolecular perezone-type [5 + 2] cycloaddition to install the BCD ring system simultaneously in a one-step, copper-catalyzed intramolecular cyclopropanation followed by BiCl3-promoted retro-aldol reaction to construct ring E and a one-pot manipulation involving reduction, lactonization, and isomerization to introduce the lactone ring F. We finally synthesized the congested BCDEF ring system of andilesin C, featuring four quaternary centers and two tertiary centers, by following a strategy with a 15-pot reaction and 11 purification operations.

Study on Determination of Molybdenum in Molybdenum Concentrate by Atomic Absorption Spectrometry Indirectly.

For the determination of molybdenum in molybdenum concentrate，lead molybdate gravimetric method was considered as standard method. In order to ensure the lead ions to be washed thoroughly from the entrained precipitate, lead molybdate precipitate was washed, filtered repeatedly, then ashed and burned. This method cannot satisfy the rapid measurement demand of mineral processing and metallurgy scientific research due to its time consuming. In the present work, molybdenum was determined by atomic absorption spectrometry indirectly and a rapid analysis method for molybdenum in molybdenum concentrate was proposed. The sample was dissolved by nitric acid, potassium chlorate and sulfuric acid, pH was adjusted by acetic acid and ammonium acetate buffer solution to pH 5～7, then a certain amount and excess of lead standard was added. Based on lead molybdate was considered as undissolved electrolyte on room temperature, the solubility of lead molybdate was 1.16×10-5g, far less than 0.01 g, was considered as the undissolved electrolyte, the electrolyte insoluble at a certain temperature can complete precipitation, usually compared with the solubility production product Qc and the relative size of constant Ksp, when Qc>Ksp, solution was supersaturated, precipitation was precipitate completely, the content of molybdenum in molybdenum concentrate was 40%~60%, the amount of lead was 0.125 0~0.150 0 g, took the minimum calculated solution lead molybdate ion product, Qc＝[Pb2+][MoO2-4]=2.51×10-5，Ksp＝1.0×10-13，QcKsp，Therefore lead molybdate precipitate can be precipitated completely, after dry filtered, the excess of lead ions were determined by atomic absorption spectrometry, the content of molybdenum was calculated by subtraction method. In this paper, the amount of acetic acid-ammonium acetate buffer solution, the amount of lead standard, time of lead molybdate precipitation, heating time and maximum amount of coexisting ions such as W6+, Sn4+, Cu2+, etc were investigated. Compared with lead molybdate gravimetric method, repeatedly washing, ashing and burning with lead molybdate were eliminated by proposed method, which was simple, easy to master and was able to cut the analysis time in half. The control experiments were conducted by lead molybdate gravimetric method and proposed method. After the results were implemented by mathematical statistics, it can be concluded that it had good accuracy and precision for the proposed method, which can be applied to rapid analysis of molybdenum in molybdenum concentrate for mineral processing and metallurgy.