Insight into the regulatory mechanism of m6A modification: From MAFLD to hepatocellular carcinoma.

In recent years, there has been a significant increase in the incidence of metabolic-associated fatty liver disease (MAFLD), which has been attributed to the increasing prevalence of type 2 diabetes mellitus (T2DM) and obesity. MAFLD affects more than one-third of adults worldwide, making it the most prevalent liver disease globally. Moreover, MAFLD is considered a significant risk factor for hepatocellular carcinoma (HCC), with MAFLD-related HCC cases increasing. Approximately 1 in 6 HCC patients are believed to have MAFLD, and nearly 40 % of these HCC patients do not progress to cirrhosis, indicating direct transformation from MAFLD to HCC. N6-methyladenosine (m6A) is commonly distributed in eukaryotic mRNA and plays a crucial role in normal development and disease progression, particularly in tumors. Numerous studies have highlighted the close association between abnormal m6A modification and cellular metabolic alterations, underscoring its importance in the onset and progression of MAFLD. However, the specific impact of m6A modification on the progression of MAFLD to HCC remains unclear. Can targeting m6A effectively halt the progression of MAFLD-related HCC? In this review, we investigated the pivotal role of abnormal m6A modification in the transition from MAFLD to HCC, explored the potential of m6A modification as a therapeutic target for MAFLD-related HCC, and proposed possible directions for future investigations.

Multi-stage virtual screening of natural products against p38α mitogen-activated protein kinase: predictive modeling by machine learning, docking study and molecular dynamics simulation.

p38α is a mitogen-activated protein kinase (MAPK), and the signaling pathways involved are closely related to the inflammation, apoptosis and differentiation of cells, which also makes it an attractive target for drug discovery. With the high efficiency and low cost, virtual screening technology is becoming an indispensable part of drug development. In this study, a novel multi-stage virtual screening method based on machine learning, molecular docking and molecular dynamics simulation was developed to identify p38α MAPK inhibitors from natural products in ZINC database, which improves the prediction accuracy by considering and utilizing both ligand and receptor information compared to any individual approach. Ultimately, we screened out two candidate inhibitors with acceptable ADMET properties (ZINC4260400 and ZINC8300300). Among the generated machine learning models, Random Forest (RF) and Support Vector Machine (SVM) performed better, with the area under the receiver operating characteristic curve (AUC) values of 0.932 and 0.931 on the test set, as well as 0.834 and 0.850 on the external validation set. In addition, the results of molecular docking and ADMET prediction showed that two compounds with appropriate pharmacokinetic properties had binding free energies less than -8.0 kcal/mol for the target protein, and the results of molecular dynamics simulations further confirmed that they were stable during the process of inhibition.

Mixture Compound Fertilizer and Super Absorbent Polymer Application Significantly Promoted Growth and Increased Nutrient Levels in Pinus massoniana Seedlings and Soil in Seriously Eroded Degradation Region of Southern China.

Pinus massoniana is the pioneer tree species in the red soil regions of southern China, however, the serious understory soil erosion and nutrient deficiency in that region are the main factors restricting the growth of P. massoniana. This field study examined the effects of compound fertilizer and super absorbent polymer (SAP) on the physiology, growth characteristics, biomass, soil nutrient, plant nutrient content, and nutrient uptake efficiency of 1-year-old P. massoniana seedlings for 2 years at Changting, Fujian in South China. One control (no fertilizer, CK) and fertilization treatments were established, namely, single compound fertilizer application (0.94, 1.89, and 3.56 g⋅plant-1) and mixture compound fertilizer and SAP application (0.94 + 1.01, 1.89 + 1.01, and 3.56 + 1.01 g⋅plant-1). Fertilization significantly improved the physiological performance, root collar diameter growth, height growth, biomass, and nutrient uptake of the seedlings. Compared with other fertilization treatments, the mixture compound fertilizer and SAP application significantly improved the seedling photosynthesis, which meant that the SAP had a significant effect on promoting photosynthesis. Under the mixture compound fertilizer and SAP application, the whole biomass of the seedlings was higher than that of all other treatments. Fertilization significantly increased the nitrogen (N), phosphorus (P), and potassium (K) content in the soils, leaves, stems, and roots of the seedlings, respectively. The P content was the main factor affecting growth characteristics and contributed to 58.03% of the total variation in seedling growth characteristics (P < 0.01). The N:P ratio of CK in the soils, leaves, and stems were higher than that of all the fertilization treatments, indicating that the severely eroded and degraded region had little P and required much of P. The principal component analysis indicated that the F2S (1.89 + 1.01 g) was the optimum fertilization amount and method in this experiment. These results provide a theoretical basis for the fertilization management of P. massoniana forests with severely eroded and degraded red soil regions.

The role of N6-methyladenosine mRNA in the tumor microenvironment.

In recent years, the most widely distributed eukaryotic messenger RNA (mRNA) modification, N6-methyladenosine (m6A), has received a large amount of interest, in part due to the development and advances of high-throughput RNA sequencing. The effects of m6A mRNA on tumor progression have been the most widely studied, and large amounts of conflicting data have been reported due to differences in tumor contexts, cell types or cell states. The majority of these studies were related to the significance of m6A mRNA on tumor cells, including on proliferation, stemness, invasion capability, etc. However, it has been noted that tumorigenesis and tumor progression cannot occur without support from the tumor microenvironment (TME), which contains multiple types of stromal cells, such as infiltrating immune cells (IICs), vascular cells, mesenchymal stem cells (MSCs), cancer-associated fibroblasts (CAFs), and various environmental factors. Here, we summarized the contributions of abnormal m6A mRNA in stromal cells within the TME and described the effects of m6A mRNA on TME remodeling.

Assessing spatial variability of soil organic carbon and total nitrogen in eroded hilly region of subtropical China.

The hilly red soil region of southern China suffers from severe soil erosion that has led to soil degradation and loss of soil nutrients. Estimating the content and spatial variability of soil organic carbon (SOC) and soil total nitrogen (STN) and assessing the influence of topography and land-use type on SOC and STN after years of soil erosion control are important for vegetation restoration and ecological reconstruction. A total of 375 topsoil samples were collected from Changting County, and their SOC and STN distributions were studied by using descriptive statistics and geostatistical methods. Elevation, slope, aspect and land-use type were selected to investigate the impacts of natural and human factors on the spatial heterogeneity of SOC and STN. The mean SOC and STN concentrations were 15.85 and 0.98 g kg-1 with moderate spatial variations, respectively. SOC and STN exhibited relatively uniform distributions that decreased gradually from the outside parts to the center of the study area. The SOC and STN contents in the study area were still at moderate and low levels after years of erosion control, which suggests that soil nutrient improvement is a slow process. The lowest SOC and STN values were at lower elevations in the center of Changting County. The results indicated that the SOC and STN contents increased most significantly with elevation and slope due to the influence of topography on the regional natural environment and soil erosion in the eroded hilly region. No significant variations were observed among different slope directions and land-use types.

Proanthocyanidin promotes functional recovery of spinal cord injury via inhibiting ferroptosis.

Improving the microenvironment of lesioned spinal cord to minimize the secondary injury is one important strategy to treat spinal cord injury (SCI). The ensuing hemorrhage after SCI has tight connection with ferroptosis. This study investigated the effects of proanthocyanidins (PACs) on SCI repair and the underlying mechanisms. Adult female mice were divided into four groups, including sham, SCI, PACs5 and PACs10 (i.p. 5 and 10 mg/kg PACs after SCI respectively). The impacts of SCI and PACs treatment on redox parameters (iron contents, TBARS, GSH, and GPX activities) and ferroptosis essential factors such as ACSL4, LPCAT3, Alox15B, Nrf2, HO-1, GPX4 were investigated. The results demonstrated that PACs treatment significantly decreased the levels of iron, TBARS, ACSL4, and Alox15B, while increased the levels of GSH, GPX4, Nrf2, and HO-1 in traumatic spinal cords. Above all, PACs improved the locomotive function of SCI mice. These results suggest that PACs might be potential therapeutics for SCI repair by inhibiting ferroptosis in SCI.

[Soil stoichiometry of Pinus massoniana forest in red soil erosion area under different management patterns]. / 红壤侵蚀退化马尾松林下不同治理模式土壤化学计量特征.

We investigated the concentrations of carbon (C), nitrogen (N), and phosphorus (P) and C:N:P stoichiometry in soil and litter of Pinus massoniana forest under four different management patterns: inefficient forest transformation, mixture of arbor with shrub and herb, shallow ditch grass planting, and being banned in serious erosion and degradation of red soil in southern China. Our findings could provide scientific basis for soil erosion control and vegetation restoration in this area. The results showed that there were significant differences in soil organic carbon (SOC), TN, TP and litter nutrient content among different management patterns. The nutrient contents in soil and litter under all the four management patterns were significantly higher than that of control, with mixture of arbor with shrub and herb having the highest concentrations. The concentrations of SOC, TN and TP decreased with the increases of soil layer. However, the shallow ditch grass planting mana-gement pattern presented as follows: the concentrations of SOC, TN and TP decreased first and then increased with the increases of soil layer, with the lowest value in 5-20 cm soil layer. There were significant differences in soil C:N, C:P, N:P and litter C:P among different management patterns, and the soil spatial variation was C:N>C:P>N:P. Excepted for mixture of arbor with shrub and herb, C:N was still at a lower level in the other management patterns, and soil C:P and N:P showed higher values overall. Litter C:N, C:P and N:P had opposite change pattern, with inefficient forest transformation and mixture of arbor with shrub and herb being much smaller than the control. Soil C:N and C:P were mainly controlled by SOC content and litter C content, and soil N:P was mainly controlled by soil TP content and litter P content. Soil stoichiometry was affected by soil water content, soil bulk density, pH, and other factors. The relationship between litter and soil nutrients was closely related and showed similar changes.

Effects of the ENSO on rainfall erosivity in the Fujian Province of southeast China.

Rainfall erosivity is one important factor that controls soil erosion. The interannual variability of rainfall erosivity in southeast China connected to the ENSO (El Niño-Southern Oscillation). Rainfall erosivity across southeast China was assessed using daily rainfall data from 60 meteorological stations during the period from 1980 to 2013. We determined that models of erosivity based on daily rainfall can accurately predict annual rainfall erosivity. This paper presents a study of the effects of Niño3.4 SST (Sea Surface Temperatures) anomalies, the SOI (Southern Oscillation Index) and the MEI (Multivariate El Niño-Southern Oscillation Index) on rainfall erosivity in the southeast of China. Results indicated that average rainfall erosivity is stronger during El Niño events and weaker during La Niña events. Correlation analyses were applied to rainfall erosivity and Niño3.4 SST anomalies, SOI, and MEI. The effects of Niño3.4 SST and SOI on rainfall erosivity are evident, as demonstrated by a statistically significant correlation (>95% confidence level). MEI was the best indicator (P<0.01) for representing the state of the ENSO. Results further indicated that 45, 31, and 40 of the 60 meteorological stations showed a significant correlation (P<0.05) between rainfall erosivity and SST anomalies, SOI, and MEI, respectively. Most of these stations were located in western Fujian Province. The ENSO was determined to exert the strongest influence on rainfall erosivity. This information would be useful in the implementation of new soil conservation strategies.

Amentoflavone enhances osteogenesis of human mesenchymal stem cells through JNK and p38 MAPK pathways.

Amentoflavone is a bioflavonoid found in a variety of traditional Chinese medicines such as Gingko and Selaginella tamariscina. It has been reported that amentoflavone has anti-inflammatory, antioxidant, antiviral and anticancer effects. However, the effect of amentoflavone on osteogenic differentiation of human mesenchymal stem cells (hMSCs) has not been studied. In this study, we aim to explore the effect of amentoflavone on the proliferation and osteogenic differentiation of hMSCs. The results showed that amentoflavone significantly enhanced the proliferation, alkaline phosphatase (ALP) activity and mineralization in hMSCs. Western blot analysis revealed that the expression of runt-related transcription factor 2 and osterix proteins was upregulated in amentoflavone-treated hMSCs. Furthermore, we investigated the possible signaling pathways responsible for osteogenic differentiation of hMSCs by amentoflavone. We found that amentoflavone significantly increased the levels of phosphorylated JNK and p-p38. The amentoflavone-induced increases of ALP and mineralization were significantly diminished when the JNK and p38 MAPK pathways were blocked by selected inhibitors (SP600125, SB203580) in hMSCs. Furthermore, in vivo evidence indicated that amentoflavone protected against the dexamethasone-induced inhibition of osteoblast differentiation in tg(sp7:egfp) zebrafish larvae. Thus, we showed for the first time that amentoflavone improves the osteogenesis of hMSCs through the JNK and p38 MAPK pathway. Amentoflavone may be beneficial in treating bone-related disorders.

Apigenin promotes osteogenic differentiation of human mesenchymal stem cells through JNK and p38 MAPK pathways.

Apigenin is a plant-derived flavonoid and has been reported to prevent bone loss in ovariectomized mice, but the role of apigenin on osteogenic differentiation of human mesenchymal stem cells (hMSCs) has not been reported. In the present study, the effect of apigenin on osteogenic differentiation of hMSCs was explored. Our results showed that apigenin treatment significantly increased alkaline phosphatase (ALP) activity and mineralization in hMSCs. RT-PCR revealed that apigenin markedly up-regulated the mRNA expression of osteopontin (OPN) and the transcription factors runt-related transcription factor 2 (Runx2). The expression of Runx2 and osterix (OSX) proteins were also increased in hMSCs differentiating into osteoblasts after treatment with apigenin. Furthermore, we investigated the signaling pathways responsible for osteogenic differentiation of apigenin in hMSCs. We found that apigenin treatment significantly increased the levels of p-JNK, p-p38 in hMSCs and addition of the inhibitors of JNK (SP600125) or p38 MAPK (SB203580) eliminated the stimulating effects of apigenin. In addition, addition of SP600125 or SB203580 also blocked apigenin-induced ALP activity, OPN, Runx2, and OSX expression and meanwhile inhibited bone nodule formation. Taken together, these findings suggest apigenin promotes the osteogenesis of hMSCs through activation of JNK and p38 MAPK signal pathways which leads to Runx2 and OSX expressions to induce the formation of bone nodule.

[A study of making use of computer-aided projection fringe system to measure breast dimension].

OBJECTIVE: To measure breast basic dimension by using computer-aided projection fringe system. METHODS: A system has been developed for measuring breast basic dimension based on computer-aided projection fringe measurement and programming software. Plastic manikins breast's SN-N (sternal notch to nipple distance), N-ML (nipple to midline distance), N-N (internipple distance), MBW (base width of breast) and N-IMF (nipple to inframammary fold distance) are measured with this system. At the same time, these items are also measured with routine ruler. RESULTS: This study indicate that the system has some merits: (1) non-touching measurement; (2) it is very rapid, the patient measured need hold his breath only 0.5 second, and all the time it takes is about 2.5 minutes; (3) the measurement's sensitivity is as high as to 0.6 mm, which meets the clinic requirement entirely; (4) the measurement's accuracy of the system is not significantly when comparing to the routine ruler's. CONCLUSIONS: Computer-aided projection fringe system for measuring breast basic dimension is feasible and advanced.

[Three-dimensional breast non-contact measurement].

OBJECTIVE: To develop a system for three-dimensional (3D) non-contact measurement of breast using computer-aided projection fringe measurement (CAPFM). METHODS: A system of 3D non-contact breast measurement was developed based on CAPFM and used for measurement of a plastic model mimicking human breast. RESULTS: The CAPFM system was capable of non-contact 3D measurement with rapid data collection (within 0.5 s) and measurement (no longer than -3 min). This system was highly automatic, and with software-controlled measurement, the sensitivity was as high as 0.6 mm (for linear measurement) and 1 ml (for volume measurement), to well meet the clinical requirements. The measurement results could be stored and expressed in numerical values or represented in vivid 2D figures and 3D images, which facilitated subsequent studies. CONCLUSION: The 3D non-contact breast measurement system on the basis of CAPFM can be helpful for medical assessment of the breast.