PC 18:1/18:1 mediates the anti-inflammatory effects of exercise and remodels tumor microenvironment of hepatocellular carcinoma.

AIM: Phosphatidylcholine (PC) is essential for membrane structural integrity and lipid-dependent signaling pathways, and is an essential component required for cancer cell growth. Using hepatocellular carcinoma (HCC) as a tumor model, this study aims to further screen phospholipid biomarkers of the tumor microenvironment and explore the anti-tumor effects and mechanisms of aerobic exercise. MAIN METHODS: The HCC of C57BL/6J mice was induced by the injection of the carcinogen diethylnitrosamine (DEN). Exercise was performed on an ungraded treadmill for weeks. The inflammation-related markers were detected by ELISA, PCR and immunohistochemistry, hepatic metabolic profile was analyzed by GC/MS, and lipid metabolism profile was further detected by lipid-targeted LC/MS. Cell culture was used to verify the anti-inflammatory effect of PC. KEY FINDINGS: Exercise reduced hepatic inflammation, tumor incidence and volume. Metabolomics analysis showed that palmitic acid is a key metabolic marker for exercise to improve tumor microenvironment. Injection of exogenous palmitic acid following exercise impaired the anti-inflammatory and anti-tumor effects of exercise. Lipid metabolomics analysis further showed that metabolites for exercise were enriched in glycerol phospholipid metabolism, including 14 phosphatidylcholines (PCs), 18 phosphatidylethanolamines (PEs), and 6 triglycerides (TGs). These biomarkers contain different lengths of fatty acid chains and different numbers of unsaturated bonds, respectively. Cell culture verified that PC (18:1/18:1) mediated lipopolysaccharide (LPS)-induced inflammation in HepG2 cell. SIGNIFICANCE: Our results suggest that exercise remodels glycerophospholipid metabolism and reduces hepatic palmitic acid loading and PC (18:1/18:1) level, thereby reconstructing a microenvironment that is hostile to HCC.

Evaluation of Cd2+ stress on Synechocystis sp. PCC6803 based on single-cell elemental accumulation and algal toxicological response.

With the development of single cell analysis techniques, the concept of precision toxicology has been proposed in recent years. Due to the heterogeneity of cells, we need to perform toxicological assessments on individual cells. Microalgae, one kind of important primary producers, play as a major pathway by which heavy metals enter the food chain and thus accumulate/transfer to higher trophic levels. Herein, the biosorption of Cd (Ex-Cd) and bioaccumulation of Cd (In-Cd) for Synechocystis sp. PCC 6803 were investigated by online 3D droplet microfluidic device combined with inductively coupled plasma mass spectrometry detection. Meanwhile, the algal toxicological responses of the algae cell to Cd2+ exposure under different concentration (50, 100, and 150 µg L - 1) and time (15 min, 24, 48 and 96 h) were studied. Combining single-cell analysis with toxicological indicators, the toxicity mechanism of Cd2+to algal was discussed. The single cell analysis results revealed heterogeneity in cellular uptake of Cd2+. The proportion of Cd-containing cells and Cd content in single algal cells all reached the maximum at 24 h. The uptake of Cd2+ occurred within 15 min under all tested exposure concentrations and a large part of Cd2+ were adsorbed on the algal cells surface. The Pearson correlation analysis showed that cell density, chlorophyll a and carotenoids were significantly negatively correlated with Cd accumulation, whereas ROS level and SOD activity were significantly positively correlated with Cd accumulation. It suggested that Cd2+accumulated intracellular would show toxic effects on the algal cells and oxidative stress is the main mechanism of Cd toxicity to algal cells. This work promotes our understanding of the toxicological responses of microalgae under Cd stress at single cells level.

Dynamic mechanism of eliminating COVID-19 vaccine hesitancy through web search.

This research focuses on the research problem of eliminating COVID-19 vaccine hesitancy through web search. A dynamic model of eliminating COVID-19 vaccine hesitancy through web search is constructed based on the Logistic model, the elimination degree is quantified, the elimination function is defined to analyze the dynamic elimination effect, and the model parameter estimation method is proposed. The numerical solution, process parameters, initial value parameters and stationary point parameters of the model are simulated, respectively, and the mechanism of elimination is deeply analyzed to determine the key time period. Based on the real data of web search and COVID-19 vaccination, data modeling is carried out from two aspects: full sample and segmented sample, and the rationality of the model is verified. On this basis, the model is used to carry out dynamic prediction and verified to have certain medium-term prediction ability. Through this research, the methods of eliminating vaccine hesitancy are enriched, and a new practical idea is provided for eliminating vaccine hesitancy. It also provides a method to predict the quantity of COVID-19 vaccination, provides theoretical guidance for dynamically adjusting the public health policy of the COVID-19, and can provide reference for the vaccination of other vaccines.

Investigation of toxic effect of mercury on Microcystis aeruginosa: Correlation between intracellular mercury content at single cells level and algae physiological responses.

Single-cell studies can help to understand individual differences and obtain atypical cellular characteristics in view of cellular heterogeneity. Herein, the accumulation of mercury (Hg) in single algae cells was studied by droplet chip-time resolved inductively coupled plasma mass spectrometry analytical system, and the relation of Hg accumulation to the physiological responses of algae cell was explored. When low concentrations of Hg2+ (5-20 µg/L) were used in the exposure experiment, the content of Hg in single cells increased in first 2 h, then decreased with further increase of exposure time to 96 h, probably due to the growth dilution effect of the algae. When exposed to 30 µg/L Hg2+, the uptake of Hg by individual cells increased over time, which was associated with increased cell membrane permeability. The exposure to Hg2+ (5-30 µg/L) inhibited the growth of algae in a concentration-dependent manner and serious growth inhibition occurred under the exposure concentration of 30 µg/L. While the exposure concentration was lower than 20 µg/L, algal cells exhibited a recover tendency due to the self-protection mechanism of algal cells. Bivariate results showed that intracellular Hg accumulation was significantly negatively correlated with cells growth in terms of OD680, photosynthetic pigments, Fv/Fm and PIabs. On the contrast, reactive oxygen species content, superoxide dismutase activity, and cell membrane permeability were significantly positively correlated with the accumulation of intracellular Hg. These results are helpful to further understand the toxic effect of Hg on algae.

Opioid and gabapentinoid prescriptions in England from 2015 to 2020.

PURPOSE: Concerns gradually arose about misuse of gabapentinoids (gabapentin and pregabalin), especially when used in combination with opioids. Because it can be a driver of usage, trends in prescribing habits may be interesting to analyse. The aim of this study is to examine the evolution of prescriptions of opioids and gabapentinoids in England from 2015 to 2020 at a regional level. METHODS: This study included data from April 2015 to February 2020, focusing on prescribing data, extracted the OpenPrescribing database. We described the evolution of the prescriptions of opioids and gabapentinoids and calculated their ratios for each month. We used Analyses of Variance (ANOVAs) to compare data between and within regions (over time). RESULTS: During this period, opioid prescriptions remained stable (from -3.3% to +2.2%/year) and increased for gabapentinoids generally (from +1.5% to +2.2%). The ratio between gabapentinoid to opioid prescriptions increased by more than 20% in 2020 compared to 2015, variably between regions (F(6,406) = [120.2]; P<0.001; LSD Test: P<0.001; ANOVA for repeated measures: P<0.05). In 2019, a decline in the ratio occurred in all regions, but only persisting in the London commissioning region in 2020 (-14.4% in comparison with 2018, 95%CI: -12.8 to -16.3). CONCLUSIONS: Gabapentinoids are increasingly prescribed in England. The ratio of gabapentinoid to opioid prescriptions in England increased from 2015 to 2020. The reclassification of gabapentinoids as controlled drugs, in 2019, may have been associated with a significant reduction, although larger prescribers may have been less influenced.

Targeting mitochondrial quality control of T cells: Regulating the immune response in HCC.

Most of the primary hepatocellular carcinoma (HCC) develops from Viral Hepatitis including Hepatitis B virus, Hepatitis C Virus, and Nonalcoholic Steatohepatitis. Herein, T cells play crucial roles combined with chronic inflammation and chronic viral infection. However, T cells are gradually exhausted under chronic antigenic stimulation, which leads to T cell exhaustion in the tumor microenvironment, and the exhaustion is associated with mitochondrial dysfunction in T cells. Meanwhile, mitochondria play a crucial role in altering T cells' metabolism modes to achieve desirable immunological responses, wherein mitochondria maintain quality control (MQC) and promote metabolism regulation in the microenvironment. Although immune checkpoint inhibitors have been widely used in clinical practice, there are some limitations in the therapeutic effect, thus combining immune checkpoint inhibitors with targeting mitochondrial biogenesis may enhance cellular metabolic adaptation and reverse the exhausted state. At present, several studies on mitochondrial quality control in HCC have been reported, however, there are gaps in the regulation of immune cell function by mitochondrial metabolism, particularly the modulating of T cell immune function. Hence, this review summarizes and discusses existing studies on the effects of MQC on T cell populations in liver diseases induced by HCC, it would be clued by mitochondrial quality control events.

The Transfer Model and Guidance Strategy of Netizens' Emotions.

In the context of the COVID-19 pandemic, a large amount of information is gathered on Internet platforms, through which people express their opinions and vent their emotions. Emotional guidance of netizens has become an important part of social governance during turbulences caused by a so-called "infodemic". This study focuses on the evolution and interaction of netizens' emotions after the occurrence of network public opinion events. First, the transfer model of netizens' emotions is constructed, and the significance of each parameter in the model is studied through simulation. Then, based on the model, we put forward the optimization method and quantitative method of guidance strategy of netizens' emotions. Finally, the empirical study proves the effectiveness of the model, which can provide a theoretical basis for the emotional guidance strategies after the outbreak of network public opinion events.