Xingqi Wang

ERK1/2 are core components of the MAPK signaling pathway and play a central role in the regulation of inflammation. Although ERK1/2 activation is well established for driving pro-inflammatory responses, accumulating evidence systematically summarized in this review demonstrates that ERK1/2 activation can also exert potent anti-inflammatory and pro-resolving effects. At the cellular level, ERK1/2 activation mediates anti-inflammatory regulation through multiple coordinated mechanisms: It promotes activation-induced cell death in T cells, drives macrophages and microglia toward anti-inflammatory phenotypes while fine-tuning their phagocytic activity, enhances efferocytosis of apoptotic cells by myeloid cells to drive inflammation resolution, inhibits dendritic cell maturation, and induces production of the key anti-inflammatory cytokine IL-10. At the molecular signaling pathway level, ERK1/2 suppresses pro-inflammatory NF-κB activity by stabilizing IκBα, directly interacting with NF-κB p65 subunit, or activating PPARγ in both immune cells and tissue-resident cells. In addition, ERK1/2 exerts anti-inflammatory effects through the Nrf2/HO-1 axis, which negatively regulates NF-κB. Further anti-inflammatory axes include the ERK1/2/CREB pathway and the FPR2/ERK1/2 pro-resolving signaling cascade. Other anti-inflammatory mechanisms include the ERK1/2/sCD14 axis that neutralizes LPS, ERK1/2-induced autophagy, and anti-inflammatory signaling triggered by diverse upstream regulators of ERK1/2. This review systematically consolidates the anti-inflammatory and pro-resolving effects of ERK1/2 activation and the underlying molecular mechanisms involved. These findings provide robust evidence that ERK1/2 activation can promote anti-inflammatory and inflammation-resolving responses and refine our understanding of the dual role of ERK1/2 as a "double-edged sword" in the regulation of inflammation.

The purple sweet potato anthocyanins (PSPA) are known for their diverse health benefits, yet their hepatoprotective effects and the mechanisms by which they combat liver fibrosis have not been thoroughly investigated. This study aimed to elucidate these effects by employing a carbon tetrachloride (CCl₄)-induced mouse model of liver fibrosis. We conducted a comprehensive analysis of the effects of PSPA on liver injury, oxidative stress, inflammation, and fibrosis-related signaling pathways. Our results demonstrate that PSPA can mitigate liver damage in mice, regulate key antioxidant enzymes such as catalase and SOD, and reduce oxidative stress as indicated by lowered MDA levels. PSPA also decrease the expression of inflammatory proteins, including CD3, CD4, CD45, IL-1β, TNF-α, and IL-17A, and reduce the accumulation of fibrotic markers like type I and III collagens and α-SMA. Additionally, PSPA have demonstrated the ability to inhibit key fibrogenic signaling proteins, including TGFβR2, p-Smad2, p-Smad3, p-PDGFRβ, p-AKT, p-ERK1/2, p-JNK1/2, and p-p38. Furthermore, we identified two potent monomers, PSPA-1 and PSPA-2, which directly target the PDGFRβ, a key player in fibrosis. The mechanism of action involves the inhibition of PDGF-B binding to PDGFRβ, thus disrupting the PDGF-B/PDGFRβ signaling pathway. These findings suggest that the hepatoprotective and antifibrotic effects of PSPA are due to their multifunctional bioactivities and the presence of specific active components that can effectively target fibrogenic protein.

Aims This study aims to investigate the effect of aerobic exercise training on BK_Ca channel in diabetic vascular smooth muscle and explore the underlying mechanism. Methods Control m/m mice and diabetic db/db mice were randomly assigned to sedentary groups (W and D) and exercise training groups (WE and DE). Mice in exercise groups underwent training sessions lasting for 12 weeks, with a speed of 12 m/min for 60 min, five times per week. The thoracic aorta was extracted isolated and examined for measurement of vascular structure, global levels of reactive oxygen species (ROS), vasodilation, and protein expression. Rat thoracic aorta vascular smooth muscle cells (USMCs) were cultured, and siRNA transfection was conducted to detect whether AMPK contributed to the regulation. ROS level and protein expression were measured. Results Compared with control mice, diabetic mice had a larger vascular medium thickness, impaired BK_Ca-mediated vasodilation, a higher level of ROS, and a lower expression of BK_Ca α, BK_Ca β1, Nrf2, p-Nrf2, p-Nrf2/Nrf2, HO-1, and p-AMPK/AMPK. Exercise training increased the expression of BK_Ca α, Nrf2, p-Nrf2, p-Nrf2/Nrf2, HO-1, and p-AMPK/AMPK. AMPK deletion led to lower ROS levels and expression of BK_Ca α, β1, Nrf2, and HO-1 in USMCs cultured in high glucose conditions. Conclusions BK_Ca channel protein expression reduction in VSMCs contributes to vasodilation and vascular remodeling dysfunction in diabetes mellitus. Aerobic exercise can promote the expression of BK_Ca channel and improve BK_Ca-mediated vascular dysfunction in diabetic VSMCs through AMPK/Nrf2/HO-1 signaling pathway.

Realgar, a traditional Chinese medicine, has notable antitumor activity and can be used in various hematologic tumor and solid tumor therapies in a wide range of clinical applications. Nanosized realgar possesses higher surface activity and enhanced therapeutic effects on cancer cells compared with those of bulk realgar. In this study, we reported the design of high-performance nanorealgar quantum dots (NR QDs) with aggregation-induced emission enhancement of crystal units (CUs) with the addition of hydrochloric acid. The enhanced fluorescence characteristics of NR QDs are associated with an optimized crystal structure obtained by accelerating the growth process of NR CUs in which the smaller NR CUs facilitate a self-assembling arrangement and a complete structural optimization process, ultimately forming regular crystallization with a size quantization effect. To improve the theranostic efficiency of NR QDs, we synthesized NR QDs coupled with a tripeptide of arginine–glycine–aspartic acid (RGD) with tumor neovascular targeting. We intravenously injected NR@RGD QDs into BALB/c mice bearing a subcutaneously transplanted breast tumor (4T1). Our results indicate that functional NR@RGD QDs are effective chemotherapeutic drugs that can anchor into the tumor endothelial cells through an active targeting effect, inhibit the angiogenesis in the tumor, and eventually “cut-off” the nutrient-rich blood supply to the tumor. This promising antiangiogenesis therapeutic strategy induces NR@RGD QDs to penetrate tumor-fenestrated vascular networks and has potential clinical value.

Background: The risk of low back pain (LBP) increases steeply during adolescence, and adolescents with LBP are more likely to have low back pain in their adult years. This study aimed to investigate the dose-response relationship between daily screen time and the risk of low back pain among children and adolescents.Methods: PubMed, the Cochrane Library, Embase, and Web of Science were searched to collect relevant studies on daily screen time and the risk of low back pain from the establishment of the database up to December 2022. Two investigators independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata16.0 was used to perform a dose-response meta-analysis and the methodological quality evaluation of the included studies.Results: The results of the meta-analysis showed that there is a positive correlation between daily computer time (OR = 1.32, 1.05–1.60), daily mobile phone time (OR = 1.32, 1.00–1.64), daily TV watching (OR = 1.07, 1.04–1.09) and the risk of low back pain, separately. The dose–response meta-analysis showed that there is a linear relationship between daily computer use and low back pain. The risk of low back pain increased by 8.2% for each 1-hour of daily computer use.Conclusions: Screen time is related to the risk of low back pain, and there is a linear relationship between daily computer use and the risk of low back pain. A number of strategic measures should be taken to prevent adolescents from developing severe low back pain.

Heavy metals in indoor dust are associated with health risks in humans. However, in Shijiazhuang, a city in northern China with severe haze, no research has been published on this topic. To determine the content, distribution characteristics, and sources of heavy metals in indoor dust in the city of Shijiazhuang, indoor dust samples from 33 sampling points in the main urban area of Shijiazhuang were collected and tested. Concentrations of Cu, Ni, Cr, Zn, Cd, and Pb were 87.0, 35.1, 104.4, 568.0, 1.980, and 187.6 mg·kg⁻¹, respectively; their levels have been discussed statistically in comparison with the reported values in other cities in China. The sources of heavy metals were analyzed using enrichment factor, correlation coefficient, and principal component analysis. The results showed that the levels of all six elements in indoor dust in Shijiazhuang exceeded the background values of soil in Hebei Province. Among these, Cd, Pb, and Zn were significantly enriched. The enrichment factors of Cu, Ni, and Cr were below 10, and their levels at different sampling points were similar, indicating their geogenic source. The corresponding pollution levels of Cd, Pb, and Zn were relatively high, and their levels at different points were significantly different and correlated, indicating that they were derived mainly from transportation. Additionally, the level of Zn was significantly affected by the indoor environment. Our findings provide a basis for conducting health risk assessments in the future.

The aim of this study was to investigate the effect of exercise training on arterial stiffness in obese and overweight children. Three databases were searched up to July 2021 for papers about exercise training and arterial stiffness in obese and overweight children. The quality of each identified study was evaluated. Effect sizes were estimated in terms of the standardized mean difference. Egger’s test and sensitivity analysis were used to assess publication bias. In total, 26 studies by 19 researchers were included in the meta-analysis. Flow-mediated dilatation (FMD), pulse wave velocity (PWV), and intima-media thickness (IMT) were improved after exercise training in obese and overweight children. Subgroup analysis showed that exercise only reduced the PWV and IMT in individuals with a BMI < 30. FMD, PWV, and IMT were improved by exercise training in participants aged below 14 years, but only FMD was increased by exercise in participants aged 14 years and above. All types of training significantly improved FMD. Aerobic exercise (AE) and high-intensity intermittent training (HIIT) reduced the PWV of the participants, but were less effective than resistance training (RT) and aerobic plus resistance training. Only HIIT significantly reduced the IMT.    Conclusions: Exercise training improved vascular endothelial function and vascular sclerosis in overweight and obese children, especially in those with a BMI < 30 and younger than 14 years. AE had a more favorable effect on arterial stiffness. What is Known: • Exercise training was a good way to lose weight and subsequently promoted vascular function in overweight and obese children. What is New: • Exercise training was more effective on the vascular endothelial function and vascular sclerosis in overweight and obese children with a BMI • Aerobic exercise had a more favorable effect on arterial stiffness, while the improvement was not effective after resistance training and combined training mode.

This paper develops a stop line aided cooperative positioning framework for connected vehicles, which creatively utilizes the location of the stop-line to achieve the positioning enhancement for a vehicular ad-hoc network (VANET) in intersection scenarios via Vehicle-to-Vehicle (V2V) communication. Firstly, a self-positioning correction scheme for the first stopped vehicle is presented, which applied the stop line information as benchmarks to correct the GNSS/INS positioning results. Then, the local observations of each vehicle are fused with the position estimates of other vehicles and the inter-vehicle distance measurements by using an extended Kalman filter (EKF). In this way, the benefits of the first stopped vehicle are extended to the whole VANET. Such a cooperative inertial navigation (CIN) framework can greatly improve the positioning performance of the VANET. Finally, experiments in Beijing show the effectiveness of the proposed stop line aided cooperative positioning framework.

The use of an antibiotic with immunomodulatory properties could be fascinating in treating multifactorial inflammatory conditions such as ulcerative colitis (UC). We report our investigations into the immunomodulatory properties of levornidazole, the S-enantiomer of ornidazole, which displayed a tremendous therapeutic potential in UC induced by dextran sodium sulfate (DSS). Levornidazole administration to DSS-colitic mice attenuated the intestinal inflammatory process, with an efficacy better than that shown by 5-amino salicylic acid. This was evidenced by decreased disease activity index, ameliorated macroscopic and microscopic colon damages, and reduced expression of inflammatory cytokines. Additionally, levornidazole displayed anti-inflammatory activity through Caveolin-1-dependent reducing IL-1β and IL-18 secretion by macrophages contributing to its improvement of the intestinal inflammation, as confirmed in vitro and in vivo. In conclusion, these results pointed out that the immunomodulatory effects of levornidazole played a vital role in ameliorating the intestinal inflammatory process, which would be crucial for the translation of its use into clinical settings.

In recent years, mouse behavior recognition has been widely used in animal behavior experiments, which is great significance to study ethology, research of animal learning and memory and analysis of drug action. However, how to quickly and accurately determine and recording the behavior of mice is still a challenge. Using manual record of mouse behavior is not only time consuming but also low accuracy; the model obtained by training C3D convolutional neural network is used for prediction and the accuracy of the obtained results cannot meet the requirements. In this paper, according to an “open field” experiment scheme in animal behavior experiments, an image preprocessing method that integrates multi-temporal mouse action pictures is proposed. With the theoretical research of deep learning convolutional neural network, the target of mouse behavior classification is finally completed. The preliminary analysis results show that this method has the characteristics of accurate classification, high accuracy and low cost. This method can obtain mouse behavior sequence by continuous batch recognition, which greatly improves the recognition efficiency.