Immunotherapeutic strategy in the management of gastric cancer: molecular profiles, current practice, and ongoing trials.

Gastric cancer (GC) is the one of the most commonly solid cancer worldwide. Although under the aggressive treatment, the poor clinical outcomes of patients with GCs have not been improved. Current studies emphasized that targeting therapies or immune response-based therapeutic strategy may be a potential approach to improve the clinical outcomes. Moreover, accumulative evidence has reported the increasing expression of PD-L1 expression in GC cells and highlighted its role in the tumor progression. Currently, great development has been established in the immune checkpoint inhibitors (ICIs) and further changed the clinical practice of GC treatment and prognosis. In addition, the combination therapies with targeting therapy or traditional therapies are expected to push the development of immunotherapies. In our present review, we predominantly focus on the biomarkers and molecular profiles for immunotherapies in GCs and highlight the role and administration of ICIs-based immunotherapeutic strategies against the GCs.

Distributional generative adversarial imitation learning with reproducing kernel generalization.

Generative adversarial imitation learning (GAIL) regards imitation learning (IL) as a distribution matching problem between the state-action distributions of the expert policy and the learned policy. In this paper, we focus on the generalization and computational properties of policy classes. We prove that the generalization can be guaranteed in GAIL when the class of policies is well controlled. With the capability of policy generalization, we introduce distributional reinforcement learning (RL) into GAIL and propose the greedy distributional soft gradient (GDSG) algorithm to solve GAIL. The main advantages of GDSG can be summarized as: (1) Q-value overestimation, a crucial factor leading to the instability of GAIL with off-policy training, can be alleviated by distributional RL. (2) By considering the maximum entropy objective, the policy can be improved in terms of performance and sample efficiency through sufficient exploration. Moreover, GDSG attains a sublinear convergence rate to a stationary solution. Comprehensive experimental verification in MuJoCo environments shows that GDSG can mimic expert demonstrations better than previous GAIL variants.

Oxidative stress in the tumor microenvironment in gastric cancer and its potential role in immunotherapy.

Gastric cancer (GC) is the fourth leading cause of cancer-related death and the fifth most common malignant tumor globally. However, the clinical efficacy of conventional therapies is limited. Currently, immunotherapy is considered an effective therapeutic strategy for the management of various cancers, especially GC, but is of only limited benefit for GC patients. Accumulating evidence has revealed that oxidative stress plays a critical role in the regulation of immune responses within the tumor microenvironment (TME), affecting the efficacy of immunotherapies. Reactive oxygen species exert critical roles in enhancing antigen presentation, regulating immune responses, and preventing immunoescape. In this review, we summarize the dominant cancer immunotherapeutic strategies and describe the interaction between oxidative stress and the immune TME. We emphasize the underlying mechanisms of the efficacy of cancer immunotherapy, which involves its effects on oxidative stress, in the context of GC. We also highlight the therapeutic potential of regulating oxidative stress to improve immunotherapies, which may have benefits for clinical practice.

Hsa_circ_0005529 promotes ZEB1 expression by regulating miR-873-5p and enhancing proliferation, invasion, and migration in gastric cancer cell lines.

BACKGROUND: Gastric cancer is a relatively common tumor. As circular RNAs (circRNAs) are documented to modulate proliferation and metastasis in various cancers, we evaluated the functions of circRNAs, in particular, hsa_circ_0005529, in gastric cancer cells. METHODS: Levels of hsa_circ_0005529 and miR-873-5p were examined by qRT-PCR, and the presence of hsa_circ_0005529 was confirmed by RNase R treatment. CCK-8, wound-healing, and Transwell assays were used to assess proliferation, migration, and invasion, respectively, while Western blotting was used to determine levels of zinc finger E-box-binding homeobox 1 (ZEB1) and dual-luciferase reporter assays to examine relationships between hsa_circ_0005529 and miR-873-5p. RESULTS: hsa_circ_0005529 was strongly expressed in gastric cancer where it stimulated tumorigenic behavior. Furthermore, hsa_circ_0005529 was shown to promote ZEB1 expression by sponging miR-873-5p, an inhibitor of ZEB1 expression. CONCLUSION: Our research showed that hsa_circ_0005529 promoted tumorigenic behavior in gastric cancer cells by adsorbing miR-873-5p to modulate ZEB1 levels. This suggests that hsa_circ_0005529 may be useful as a biomarker and target for diagnosing and treating gastric cancer.

Dissipation and distribution of chlorpyrifos in selected vegetables through foliage and root uptake.

Dissipation, distribution and uptake pathways of chlorpyrifos were investigated in pakchoi (Brassica chinensis L.) and lettuce (Lactuca sativa) with foliage treatments under a greenhouse trial and root treatments under a hydroponic experiment. The dissipation trends were similar for chlorpyrifos in pakchoi and lettuce with different treatments. More than 94% of chlorpyrifos was degraded in the samples for both of the vegetables 21 days after the foliage treatments. For the root treatment, the dissipation rate of chlorpyrifos in pakchoi and lettuce at the low concentration was greater than 93%, however, for the high concentrations, the dissipation rates were all under 90%. Both shoots and roots of the vegetables were able to absorb chlorpyrifos from the environment and distribute it inside the plants. Root concentration factor (RCF) values at different concentrations with the hydroponic experiment ranged from 5 to 39 for pakchoi, and from 14 to 35 for lettuce. The translocation factor (TF) representing the capability of the vegetables to translocate contaminants was significantly different for pakchoi and lettuce with foliage and root treatments. The values of TF with foliage treatments ranged from 0.003 to 0.22 for pakchoi, and from 0.032 to 1.63 for lettuce. The values of TF with root treatments ranged from 0.01 to 0.17 for pakchoi, and from 0.003 to 0.23 for lettuce. Significant difference of TF was found between pakchoi and lettuce with foliage treatments, and at high concentrations (10 and 50 mg L(-1)) with root treatments as well. However, there was no significant difference of TF between pakchoi and lettuce at 1 mg L(-1) with root treatment.

Suppression of Chlorantraniliprole Sorption on Biochar in Soil-Biochar Systems.

The sorption behavior of chlorantraniliprole (CAP) by biochar and effect of soil extracts on sorptivity in soil-biochar systems were examined. The results showed that biochar amendment could enhance the sorption of CAP in soils. The values of K F increased significantly when the soils were amended with 0.5 % BC850, which were from 1.54 to 196.5. The indigenous sorptivity of biochar was suppressed after it was applied to the soils. The degree of biochar sorptivity attenuation in different soil-biochar systems varied with the properties of soil water soluble matters. Sorption of CAP by biochar from the five soil extracts was found to be lower than that from a CaCl2 solution. The calculated K d values at C w of 0.01 mg kg(-1) for biochar sorption of CAP from CaCl2 solution were 21.4-26.6 times of that from soil extracts. Aging of biochar in soil extract reduced CAP sorption by up to 85 %.

Persistence and dissipation of chlorpyrifos in Brassica chinensis, lettuce, celery, asparagus lettuce, eggplant, and pepper in a greenhouse.

The residue behavior of chlorpyrifos, which is one of the extensively used insecticides all around the world, in six vegetable crops was assessed under greenhouse conditions. Each of the vegetables was subjected to a foliar treatment with chlorpyrifos. Two analytical methods were developed using gas chromatography equipped with a micro-ECD detector (LOQ = 0.05 mg kg(-1)) and liquid chromatography with a tandem mass spectrometry (LOQ = 0.01 mg kg(-1)). The initial foliar deposited concentration of chlorpyrifos (mg kg(-1)) on the six vegetables followed the increasing order of brassica chinensis

Aggregation and fusion of low-density lipoproteins in vivo and in vitro.

Low-density lipoproteins (LDLs, also known as 'bad cholesterol') are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a single copy of apolipoprotein B (550 kDa). An early sign of atherosclerosis is the accumulation of LDL-derived lipid droplets in the arterial wall. According to the widely accepted 'response-to-retention hypothesis', LDL binding to the extracellular matrix proteoglycans in the arterial intima induces hydrolytic and oxidative modifications that promote LDL aggregation and fusion. This enhances LDL uptake by the arterial macrophages and triggers a cascade of pathogenic responses that culminate in the development of atherosclerotic lesions. Hence, LDL aggregation, fusion, and lipid droplet formation are important early steps in atherogenesis. In vitro, a variety of enzymatic and nonenzymatic modifications of LDL can induce these reactions and thereby provide useful models for their detailed analysis. Here, we summarize current knowledge of the in vivo and in vitro modifications of LDLs leading to their aggregation, fusion, and lipid droplet formation; outline the techniques used to study these reactions; and propose a molecular mechanism that underlies these pro-atherogenic processes. Such knowledge is essential in identifying endogenous and exogenous factors that can promote or prevent LDL aggregation and fusion in vivo and to help establish new potential therapeutic targets to decelerate or even block these pathogenic reactions.

Kinetic analysis of thermal stability of human low density lipoproteins: a model for LDL fusion in atherogenesis.

Fusion of modified LDL in the arterial wall promotes atherogenesis. Earlier we showed that thermal denaturation mimics LDL remodeling and fusion, and revealed kinetic origin of LDL stability. Here we report the first quantitative analysis of LDL thermal stability. Turbidity data show sigmoidal kinetics of LDL heat denaturation, which is unique among lipoproteins, suggesting that fusion is preceded by other structural changes. High activation energy of denaturation, E(a) = 100 ± 8 kcal/mol, indicates disruption of extensive packing interactions in LDL. Size-exclusion chromatography, nondenaturing gel electrophoresis, and negative-stain electron microscopy suggest that LDL dimerization is an early step in thermally induced fusion. Monoclonal antibody binding suggests possible involvement of apoB N-terminal domain in early stages of LDL fusion. LDL fusion accelerates at pH < 7, which may contribute to LDL retention in acidic atherosclerotic lesions. Fusion also accelerates upon increasing LDL concentration in near-physiologic range, which likely contributes to atherogenesis. Thermal stability of LDL decreases with increasing particle size, indicating that the pro-atherogenic properties of small dense LDL do not result from their enhanced fusion. Our work provides the first kinetic approach to measuring LDL stability and suggests that lipid-lowering therapies that reduce LDL concentration but increase the particle size may have opposite effects on LDL fusion.