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Macropinocytosis, an evolutionarily conserved, actin-dependent form of endocytosis, is involved in various physiological processes, including nutrient absorption, antigen presentation, and cell signaling transduction and migration. Oncogene activation and tumor suppressor inactivation induce macropinocytosis in tumors in the digestive system, involved in tumorigenesis and progression, whereas the inhibition of macropinocytosis slows the aggressive phenotype of digestive system tumors and improves the efficacy of anti-tumor drugs. Macropinocytosis can also be used as a delivery route for anti-tumor drugs. Therefore, macropinocytosis has been widely studied to develop new methods for the treatment of digestive system tumors.This paper reviews the role of macropinocytosis in the body, the regulation of macropinocytosis-related signaling pathway, as well as the mechanism of macropinocytosis in colorectal cancer, pancreatic ductal adenocarcinoma, liver cancer and other digestive system tumors, to provide reference for related researches.

Gastric precancerous lesions (GPL) are a special histopathological stage before the occurrence of gastric cancer. Effective treatment of GPL is the key to preventing its progression to gastric cancer. GPL has a high level of inflammation in gastric mucosa, and a large number of inflammatory cells, inflammatory factors and inflammatory mediators are metabolized at a high level, which increases oxygen consumption and leads to the formation of a hypoxia microenvironment in gastric mucosa at the GPL stage, which is conducive to the initiation of mitochondrial autophagy and glucose metabolism reprogramming. As a conserved biological process, mitochondrial autophagy exists in various tissues and cells of the body. It can form autophagosome to wrap mitochondria with damaged functions and bind with lysosomes to digest and reuse target mitochondria. Appropriate autophagy level can prevent excessive proliferation of GPL heterotype cells and inhibit the progress of GPL. However, mitochondrial autophagy activity is inhibited during the course of GPL, and the activity of glycometabolic reprogramming into glycolysis is increased during GPL. Glycolysis is a way of energy metabolism in the hypoxia state of cells, which can accelerate the energy supply of cells and the proliferation of abnormal cells, and thus accelerate the deterioration of GPL. Some evidences suggest that there may be a mutually restricting relationship between mitochondrial autophagy and glycolysis reprogramming. The inhibition of autophagy in GPL can increase glycolysis activity on the one hand, while the increase of autophagy inhibits glycolysis activity on the other hand. At present, the specific relationship and mechanism of autophagy and glycolysis are not clear, however, the complex pathological environment of GPL gastric mucosa composed of hypoxia, bacterial infection, inflammation, oxidative stress, activation disorder of signal molecules and other factors may be the key to the low autophagy level and high glycolysis activity. Hypoxia-inducible factor 1α (HIF-1α), which is involved in hypoxia adaptation, is stably expressed in gastric mucosa at the GPL stage and acts as a switch to initiate autophagy and glycolysis. However, HIF-1α seems to be more involved in the regulation of glycolysis in the pathological process of GPL. The cause of this change may be related to the above-mentioned pathological factors. H. pylori infection, activation of phosphoinositide 3-kinase (PI3K)/protein kinase (AKT)/mammalian target of rapamycin (mTOR) pathway and other factors inhibit autophagy. However, the continuous accumulation of reactive oxygen species (ROS) after autophagy inhibition and the aggravation of inflammation caused by H. pylori infection can promote a series of signal interactions and synergies among nuclear factor kappa-B (NF-Κb), signal transducer and activator of transcription 3 (STAT3) and PI3K/AKT/mTOR signaling pathways, and thus indirectly affect HIF-1α to promote glycolysis or directly improve glycolysis level. HIF-1α may be more involved in the activation of glycolysis due to the regulation of GPL pathological microenvironment and its upstream complex signals, thus unable to fully activate BNIP-3 mediated hypoxia-initiated autophagy, leading to the down-regulation or inhibition of autophagy level, and the inhibition of autophagy indirectly promotes the improvement of glycolysis level, forming a vicious cycle, and ultimately leading to the deterioration of GPL. This article reviewed the research progress of hypoxia-induced mitochondrial autophagy and glucose metabolism reprogramming in gastric precancerous lesions.

Hepatocellular carcinoma (HCC) is the most common pathological type of primary liver cancer, with high fatality rate. The pathogenesis of HCC is complex, and the specific occurrence and development mechanism is still in the exploratory stage. CircRNA is a special endogenous noncoding RNA and mainly participates in the regulation of gene expression at the transcriptional and posttranscriptional levels. By regulating gene transcription, it acts as a molecular sponge of miRNA, participates in protein translation, and interacts with RNA binding protein (RBP). CircRNA is involved in the occurrence and development of HCC. Its abnormal expression in HCC cells is related to the pathological characteristics of HCC tissue, regulates the expression of downstream target genes, miRNA and proteins, participates in the proliferation, migration, invasion and apoptosis of HCC cells, and regulates tumor microenvironment and signal pathways, suggesting that circRNA may be a potential novel biomarker and therapeutic target for the diagnosis and prognosis of HCC. This paper reviews the biological mechanism of circRNA, its role in HCC, and research progress in diagnosis and treatment.

Hepatocellular carcinoma (HCC) is a common malignant tumor of digestive tract. Its occurrence is multistage: hepatitis-cirrhosis-precancerous lesion-HCC. The mechanism of malignant transformation from precancerous lesions to hepatocellular carcinoma is not completely clear, which may be affected by the polarization direction of Kupper cells. Kupffer cells are special monocyte macrophages in the liver. They can differentiate into M1 and M2 phenotypes in different microenvironments. They have different functions and play a role in inhibiting or promoting cancer in hepatocellular carcinoma. Studies have found that a variety of miRNAs and LncRNAs can target Kupffer polarization-related proteins to regulate their polarization direction, thereby affecting the occurrence, development and malignant transformation of precancerous lesions of the liver and reducing the incidence of liver cancer. This article mainly elaborates the frontier progress of the above researches, and provides a reference for the prevention and treatment of hepatocellular carcinoma.

Metal‐doped porous carbon matrix composites are considered as outstanding H2S cataluminescence sensing materials for their good sulfur tolerance and high cataluminescence activity. In this work, an Fe‐doped MOF‐derived N‐rich porous carbon nanoframe was successfully fabricated using the pyrolysis of Fe‐doped ZIF‐8 in an Ar atmosphere at a temperature of 900°C, and used for H2S cataluminescence sensing. Along with zinc volatilization, the obtained porous carbon nanoframe not only had high specific surface area and abundant voids, but also had well dispersed Fe species doped in the skeleton. Compared with Fe2O3/ZnO composites derived from the same precursor but different pyrolysis terms, this as‐prepared Fe‐doped N‐rich porous carbon presented a three times increase in the cataluminescence intensity towards H2S, attributed to the porous carbon skeleton that is indispensable for dispersing catalytic active sites and providing more absorptive surface and voids. Comparably, this proposed sensor demonstrated high sensitivity and good selectivity, with the detection range of 1.57–19.58 μg·ml−1 and detection limit of 0.13 μg·ml−1 towards H2S. This work may provide a new pathway for preparing catalysts for cataluminescence sensing with better metal distribution, higher specific surface area, and richer pores than ever before. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of depression is related to the NOD-like receptor protein 3 (NLRP3) inflammasome activation and low level of mitophagy. In traditional Chinese medicine, Paeonia lactiflora Pall is a common herb as a possible treatment for depression. As a main and active constituent of P. lactiflora Pall, paeoniflorin (PF)'s mechanisms of antidepression effects are not evidently unstated. Therefore, this study intended to explore whether PF can prevent depression-like behavior by conquering NLRP3 inflammasome activation and whether PF prevents NLRP3 inflammasome activation via upregulating mitophagy. Materials and Methods: Ten of a total of 50 rats were selected randomly as the control group. After establishment of the chronic unpredictable mild stress (CUMS) model, CUMS rats were randomly divided into four groups: CUMS group, fluoxetine hydrochloride group, PF group, and PF + cyclosporine A group. After 3 weeks of drug involvement, behavioral tests were measured. The protein expressions of PINK-1, Parkin, Beclin-1, LC3B, NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1 p20, interleukin-1β (IL-1β), and IL-18 were spotted with Western Blot method. Results: PF upturned stress persuaded behavioral changes and PF treatment augmented sucrose consumption rates (P < 0.01) in sucrose preference test and reduced the immobility time (P < 0.01) in forced swimming test of CUMS rats. PF also improved the levels of mitophagy-related proteins PINK-1, Parkin, Beclin-1, and LC3B (P < 0.01) in the hippocampus. Moreover, PF decreased the levels of NLRP3 inflammasome-related proteins (NLRP3, ASC, caspase-1 p20 antibody, IL-1β, and IL-18 [P < 0.01]) tempted by stress. Conclusion: PF advances depression in CUMS rats, reduced the inflammatory injury in the hippocampus of CUMS rats. Hence, based on those facts, NLRP3 inflammasome activation is accomplished by inhibiting its effect on mitophagy. [ABSTRACT FROM AUTHOR]