Tumor-associated macrophages regulate gastric cancer cell invasion and metastasis through TGFβ2/NF-κB/Kindlin-2 axis

Objective: Recent studies have shown that tumor-associated macrophages(TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis of gastric cancer(GC) cells through the Kindlin-2 pathway. However, the mechanism needs to be clarified.Methods: THP-1 monocytes were induced by PMA/interleukin(IL)-4/IL-13 to establish an efficient TAM model in vitro and M2 macrophages were isolated via flow cytometry. A dual luciferase reporter system and chromatin immunoprecipitation(Ch IP) assay were used to investigate the mechanism of transforming growth factor β2(TGFβ2) regulating Kindlin-2 expression. Immunohistochemistry was used to study the relationships among TAM infiltration in human GC tissues, Kindlin-2 protein expression, clinicopathological parameters and prognosis in human GC tissues. A nude mouse oncogenesis model was used to verify the invasion and metastasis mechanisms in vivo.Results: We found that Kindlin-2 expression was upregulated at both m RNA and protein levels in GC cells cocultured with TAMs, associated with higher invasion rate. Kindlin-2 knockdown reduced the invasion rate of GC cells under coculture condition. TGFβ2 secreted by TAMs regulated the expression of Kindlin-2 through the transcription factor NF-кB. TAMs thus participated in the progression of GC through the TGFβ2/NF-κB/Kindlin-2 axis. Kindlin-2 expression and TAM infiltration were significantly positively correlated with TNM stage, and patients with high Kindlin-2 expression had significantly poorer overall survival than patients with low Kindlin-2 expression. Furthermore, Kindlin-2 promoted the invasion of GC cells in vivo.Conclusions: This study elucidates the mechanism of TAMs participating in GC cell invasion and metastasis through the TGFβ2/NF-κB/Kindlin-2 axis, providing a possibility for new treatment options and approaches.

Landscape of cell heterogeneity and evolutionary trajectory in ulcerative colitis-associated colon cancer revealed by single-cell RNA sequencing

Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at the single-cell level.Methods:Fresh samples of tumor tissues and adjacent UC tissues from a CAC patient with pT3N1M0 stage cancer were examined by single-cell RNA sequencing(scRNA-seq).Data from The Cancer Genome Atlas(TCGA)and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with patient prognosis.Results:Ultimately,4,777 single-cell transcriptomes(1,220 genes per cell)were examined,of which 2,250(47%)and 2,527(53%)originated from tumor and adjacent UC tissues,respectively.We defined the composition of cancer-associated stromal cells and identified six cell clusters,including myeloid,T and B cells,fibroblasts,endothelial and epithelial cells.Notable pathways and transcription factors involved in these cell clusters were analyzed and described.Moreover,the precise cellular composition and developmental trajectory from UC to UCassociated colon cancer were graphed,and it was predicted that CD74,CLCA1,and DPEP1 played a potential role in disease progression.Conclusions:scRNA-seq technology revealed intra-tumor cell heterogeneity in UC-associated colon cancer,and might provide a promising direction to identify novel potential therapeutic targets in the evolution from UC to CAC.

Salt effect on MUCT system performance of nitrogen and phosphorus removal

The effect of salinity on biological nitrogen and denitrifying phosphorus removal was investigated in a Modified University of Cape Town(MUCT)system.Removal rates of COD,NH_(4)^(+)-N,NO_(3)^(-)-N,NO_(2)^(-)-N,phosphorus and the sludge characteristics at salt concentrations(0.0,3.2,6.4,11.2 and 16.0 g L^(-1))were analyzed.With the salt concentration increasing,all the COD,NH_(4)^(+)-N,TN and TP removal rates exhibited a trend of decline,and exhibited an initial reduction and subsequent increase at every stage of salt concentration.NH_(4)^(+)-N,TN and TP removal rates were 92.7%,51.5%and 67.2%in 16 g L^(-1) salt concentration,respectively.And they were outperformed the literature reported and acceptable in practical applications.When the salinity of wastewater changed from 0.0 to 16.0 g L^(-1),the biomass yield coefficients increased from 0.0794 to 0.126 g VSS/g COD.Increased salinity had a detrimental effect on phosphorus-accumulating organisms(PAOs)and denitrifying PAOs(DPAOs)(especially DPAOs).Therefore,phosphorus removal gradually depended on PAO.The simultaneous nitrification and denitrification(SND)rate and nitrogen removal rate(including nitrification rate,denitrification rate,and total nitrogen removal rate)gradually decreased with the increased salinity.

A biodegradable magnesium surgical staple for colonic anastomosis: In vitro and in vivo evaluation

Staplers have been widely used in the clinical treatment of gastrointestinal reconstruction.However,the current titanium(Ti)staple will remain in the human body permanently,resulting in some adverse effects.In this study,we developed a type of biodegradable staple for colonic anastomosis using 0.3 mm diameter magnesium(Mg)alloy wires.The wire surface was modified by micro-arc oxidation treatment(MAO)and then coated with poly-L-lactic acid(PLLA)to achieve a moderate degradation rate matching the tissue healing process.The results of tensile tests on isolated porcine colon tissue anastomosed by Mg and Ti staples showed that the anastomotic property of Mg staples was almost equal to that of Ti staples.The in vitro degradation tests indicated the dual-layer coating effectively enhanced the corrosion resistance and maintained the tensile force of the coated staple stable after 14-day immersion in the simulated colonic fluid(SCF).Furthermore,24 beagle dogs were employed to conduct a comparison experiment using Mg-based and clinical Ti staples for 90-day implantation by ent-to-side anastomosis of the colon.The integrated structure of Mg-based staples was observed after 7 days and completely degraded after 90 days.All animals did not have anastomotic leakage and stenosis,and 12 dogs with Mg-based staples fully recovered after 90 days without differences in visceral ion levels and other side effects.The favorable performance makes this Mg-based anastomotic staple an ideal candidate for colon reconstruction.