CD168+ macrophages promote hepatocellular carcinoma tumor stemness and progression through TOP2A/ß-catenin/YAP1 axis.

Liver cancer stem-like cells (LCSCs) are the main cause of heterogeneity and poor prognosis in hepatocellular carcinoma (HCC). In this study, we aimed to explore the origin of LCSCs and the role of the TOP2A/ß-catenin/YAP1 axis in tumor stemness and progression. Using single-cell RNA-seq analysis, we identified TOP2A+CENPF+ LCSCs, which were mainly regulated by CD168+ M2-like macrophages. Furthermore, spatial location analysis and fluorescent staining confirmed that LCSCs were enriched at tumor margins, constituting the spatial heterogeneity of HCC. Mechanistically, TOP2A competitively binds to ß-catenin, leading to disassociation of ß-catenin from YAP1, promoting HCC stemness and overgrowth. Our study provides valuable insights into the spatial transcriptome heterogeneity of the HCC microenvironment and the critical role of TOP2A/ß-catenin/YAP1 axis in HCC stemness and progression.

Single-cell RNA Sequencing Analysis Reveals New Immune Disorder Complexities in Hypersplenism.

Hypersplenism (HS) is a concomitant symptom of liver or blood disease. Not only does the treatment of HS face challenges, but the transcriptome of individual cells is also unknown. Here, the transcriptional profiles of 43,037 cells from four HS tissues and one control tissue were generated by the single-cell RNA sequencing and nine major cell types, including T-cells, B-cells, NK cells, hematopoietic stem cells, neutrophil cells, mast cells, endothelial cells, erythrocytes, and dendritic cells were identified. Strikingly, the main features were the lack of CCL5+ B-cells in HS and the presence of SESN1+ B cells in HS with hepatocellular carcinoma (HS-HCC). In cell-cell interaction analysis, CD74-COPA and CD94-HLA-E in HS were found to be up-regulated. We further explored HS-specifically enriched genes (such as FKBP5, ADAR, and RPS4Y1) and found that FKBP5 was highly expressed in HCC-HS, leading to immunosuppression. Taken together, this research provides new insights into the genetic characteristics of HS via comprehensive single-cell transcriptome analysis.

MicroRNA-203-3p inhibits the proliferation, invasion and migration of pancreatic cancer cells by downregulating fibroblast growth factor 2.

Aberrant expression of fibroblast growth factor 2 (FGF2) is a major cause of poor prognosis in patients with pancreatic cancer. MicroRNA (miRNA/miR) miR-203-3p is a newly identified miRNA that can affect the biological behavior of tumors. The present study investigated the function of miR-203-3p on the regulation of FGF2 expression, and its role in pancreatic cancer cell proliferation, apoptosis, invasion and migration. Reverse transcription-quantitative PCR was used to determine the mRNA expression levels of miR-203-3p and FGF2 in vitro. Cell Counting Kit-8, Annexin V-APC/7-AAD double-staining Apoptosis Detection kit, wound healing and Transwell assays were used to determine the proliferation, apoptosis, migration and invasion of pancreatic cancer cells. The binding of miR-203-3p to FGF2 was assessed by a luciferase reporter assay. The results demonstrated that miR-203-3p expression was downregulated in pancreatic cancer cells. Gain- and loss-of-function experiments indicated that miR-203-3p inhibited the proliferation, migration and invasion, and promoted the apoptosis of pancreatic cancer cells in vitro. In addition, it was found that alteration of miR-203-3p abolished the promoting effects of FGF2 on pancreatic cancer cells. The present study demonstrated that FGF2 significantly promoted the proliferation, invasion and migration of pancreatic cancer cells. The mechanism involved the binding of miR-203-3p to the 3'-untranslated region of FGF2 mRNA, resulting in the downregulation of FGF2. In conclusion, miR-203-3p inhibited FGF2 expression, regulated the proliferation and inhibited the invasion and migration of pancreatic cancer cells.

The Role of Prefoldin and Its Subunits in Tumors and Their Application Prospects in Nanomedicine.

Prefoldin (PFDN) is a hexameric chaperone complex that is widely found in eukaryotes and archaea and consists of six different subunits (PFDN1-6). Its main function is to transfer actin and tubulin monomers to the eukaryotic cell cytoplasmic chaperone protein (c-CPN) specific binding during the assembly of the cytoskeleton, to stabilize the newly synthesized peptides so that they can be folded correctly. The current study found that each subunit of PFDN has different functions, which are closely related to the occurrence, development and prognosis of tumors. However, the best characteristics of each subunit have not been fully affirmed. The connection between research and tumors can change the understanding of PFDN and further extend its potential prognostic role and structural function to cancer research and clinical practice. This article mainly reviews the role of canonical PFDN and its subunits in tumors and other diseases, and discusses the potential prospects of the unique structure and function of PFDN in nanomedicine.

Electroacupuncture Modulates Resting-State Functional Connectivity in the Default Mode Network for Healthy Older Adults.

Aging involves cognitive decline and prominent alterations in brain activity. Electroacupuncture (EA), a traditional Chinese medicine approach, is demonstrated to be effective in improving cognitive function of older adults. However, the specific neural mechanism underlying this modulation effect remains unclear. In this study, we used functional magnetic resonance imaging (fMRI) to investigate whether EA could improve cognitive performance of community-dwelling older adults and whether these potential improvements are associated with the EA-induced brain functional connectivity alterations. Thirty healthy older adults were recruited and randomly assigned to the EA group and the control group. Behaviorally, we observed an EA-induced improvement in cognitive performance of older adults in the Montreal Cognitive Assessment. On a neural perspective, the EA intervention significantly increased the functional connectivity within the default mode network. Moreover, we found a positive association between the improvement in delayed memory performance and the alterations in the ventral medial prefrontal cortex-hippocampal formation connectivity in the EA group. This study extends previous findings by showing that healthy older adults exhibit neural plasticity manifested as increased functional connectivity after EA sessions, which could induce therapeutic effects in the treatment of neurodegenerative diseases.

[Effects and Differences of the Release of Dissolved Organic and Inorganic Phosphorus in Different Sediments Covered by Different Materials of Erhai Lake].

In this work, the effects of four covering materials on the release of total dissolved phosphorus (DTP), dissolved organic phosphorus (DOP), and soluble reactive P (SRP) in different sediments of Erhai Lake were simulated. The results showed that the max release of DTP was reduced in covering material, which attributed to the changes of pH, Eh and characteristics of dissolved organic matter (DOM) by the effect of covering material. The application of iron oxide material significant reduced the release of DTP in the northern and southern part of the lake, with decrease rate of 44.3% and 35.7%, respectively. by contrast, the application of aluminum oxide material significant reduced the release of DTP in the middle part sediment, with decrease rate of 29.6%. Furthermore, the release of SRP and DOP in different sediments has significant difference after added different material. In northern part of sediment, the release of SRP and DOP reduced by 35.6% and 36.2% after added iron oxide material. This is because iron oxide can reduce the pH and Eh but increase the availability of DOM in northern, and then benefits for inhibiting the release of SRP and DOP. In the middle, the release of sediment SRP and DOP reduced by 28.9% and 31.6% after added aluminum oxide material. This is because the aluminum oxide can facilitate the availability of DOM in middle, and then inhibits the release of SRP and DOP. In southern part of the lake, the release of sediment SRP and DOP reduced by 47.4% and 16.5% after added iron oxide material. This is largely attributed to the effect of iron oxide on the pH and Eh. Therefore, to control the release of P in the sediment from Lake Erhai, iron oxide material should be selected in the northern and southern parts, whereas aluminum oxide should be selected in the middle part of the lake.

[Relationship between the DO and the environmental factors of the water body in Lake Erhai].

The contents of DO and nitrogen (N), phosphorus (P), chlorophyll a in water from Lake Erhai were analysed by combining the nitrogen and phosphorus forms in sediment. The results indicated that the DO contents of the water from Lake Erhai varied from 6.61 to 7.42 mg/L from 1992 to 2009, which is generally decreased. The minimum mean value was 6.42 mg/L in September. The trend of the DO contents from north to south was decreasing, and also decreased with the increasing of the water depth in Lake Erhai, the DO content was 5.15 mg/L at the water bottom. The relationship between the contents of DO and N, P was negative, and the relativity of different months was greater than that of different years. The relationship between the contents of DO and the contents of labile-P, organic-P, NH4(+) -N in sediment was negative, which was positive with the contents of Fe/Al-P, inorganic P and NO3(-) -N. The relationship between the contents of DO and chlorophyll a in water was negative, which indicated that Lake Erhai is aerobic, and is approaching anaerobic gradually. With the increasing of released content of N and P, the increasing of alga biomass was accelerated and the worsening of water body eutrophication also can be promoted by the decreased DO content in water from Lake Erhai.

[Effect of different type sediments on transformation of phosphorus forms and growth of Myriophyllum spicatum].

The changes of the different phosphorus (P) forms in sediments, overlying water and the diversity of dry weight and root forms of Myriophyllum spicatum were studied using different type sediments under simulating condition. The characteristic of transformation of P forms and growth of submerged plant Myriophyllum spicatum were illustrated. The results indicated that the P release was promoted by adding the silver sand in sediment, and their P concentrations in the overlying water were increased. The chemical characteristic of the sediments were changed by adding NH4 Cl, which restrained the P release from their sediments and decreased the P concentration in their overlying water. About 49%, 107% of their plant, root dry weight and 19% root length of Myriophyllum spicatum from different treatments were raised by adding silver sand in sediments. The root growths of the Myriophyllum spicatum from different treatments were restrained and their agings were promoted by adding NH4 Cl in sediments. The P release from sediments were accelerated by the growth of Myriophyllum spicatum, and the early decay of Myriophyllum spicatum can increase the P accumulation in sediment. The changing trend of different P forms in the sediments decreased firstly, and then increased with the Myriophyllum spicatum growthing, their contents of Fe/Al-P form in sediments varied greatly (41%-57%). The P release and adsorption in sediments were mainly affected by their root length index of Myriophyllum spicatum from different treatments. The P release in sediment was accelerated through their changing penetrate capacity by root diameter increasing.

[Phosphate adsorption characteristics onto the sediments from shallow lakes in the middle and lower reaches of the Yangtze River].

Adsorption isotherms and kinetics of phosphate onto the 11 sediments taken from shallow lakes in the middle and lower reaches of the Yangtze River were determined in laboratory, and the effect of physical and chemical properties of the sediments on its phosphate adsorption characteristics was also analyzed. The results indicate that: (1) The process of phosphate adsorption onto sediments mainly occurred within 0-10 h, the maximum adsorption rates occurred within 0-0.5 h, and then attends to a dynamic equilibrium; (2) Between the NAP and its organic matter, CEC, total phosphorus, inorganic phosphorus, organic phosphorus, Fe/Al-phosphorus and total nitrogen have remarkable positive correlation; between the maximum adsorption of phosphate and its CEC, inorganic phosphorus, organic matter and total phosphorus have remarkable negative correlation; between the total maximum adsorption of phosphate and its organic matter, CEC, total phosphorus, inorganic phosphorus, organic phosphorus, Fe/Al-phosphorus and total nitrogen have remarkable positive correlation; (3) As regards water quality of the shallow lakes in the middle and lower reaches of the Yangtze River at present, its sediment exists desorption. Between the adsorption-desorption equilibrium concentrations of phosphate onto the sediments and its organic matter, CEC, total nitrogen, the total phosphorus and the content of every form phosphorous have a remarkable positive correlation. Even the sediment from heavily polluted lake also has the tendency to release phosphate into the overlying water in this study.