Elucidating the interplay of ferroptosis-related genes in keloid formation:Insights from bioinformatics analysis

Background:Keloids are benign skin tumors characterized by fibroblast proliferation,tumor-like biological behavior,and excessive deposition of extracellular matrix in wounded skin.Ferroptosis,a type of programmed cell death,is critical in tumor pathogenesis.We aimed to investigate the role of ferroptosis in keloid formation.Methods:We downloaded public high-throughput sequencing raw count data(GSE92566),containing three normal skin and four keloid samples,from the Gene Expression Omnibus database.Ferroptosis-related genes were obtained from the Ferroptosis database website.The ferroptosis-related differentially expressed genes(FRDEGs)were obtained by merging differentially expressed genes with ferroptosis-related genes.The FRDEGs were then used for Gene Ontology,Kyoto Encyclopedia of Genes and Genomes,Gene Set Enrichment Analysis,proteinprotein interaction(PPI)network,and microRNA(miRNA)-mRNA network analysis.Finally,real-time quantitative polymerase chain reaction(RT-qPCR)was performed to validate our findings.Results:We found 25 FRDEGs,including 8 up-regulated and 17 down-regulated genes.Pathway enrichment analysis revealed that the Hippo and transforming growth factorβsignaling pathways were significantly upregulated in keloids.In contrast,regulation of the peroxisome proliferator-activated receptor signaling pathway,glutathione metabolism,and unsaturated fatty acid metabolic process were down-regulated.PPI and FRDEGs hub networks were constructed using the STRING database and Cytoscape software.Ten hub genes were identified,including PLA2G6,RARRES2,SNCA,CYP4F8,CDKN2A,ALOX12,FABP4,ALOX12B,NEDD4,and NEDD4L.We constructed a miRNA-mRNA network,which predicted hsa-mir-155-5p,hsa-let-7b-5p,hsa-mir-124-3p,hsa-mir-145-5p,hsa-mir-328-3p,hsa-mir-24-3p,and hsa-mir-10b-5p as the most connected miRNAs regulating ferroptosis in keloids.Finally,we verified the expression levels of the hub genes by RT-qPCR,which confirmed that ALOX12,ALOX12B,and CYP4F8 expression were reduced in keloids.Conclusions:This study provides novel information on ferroptosis-mediated keloid pathogenesis,underscoring the importance of further research in this area to unlock new therapeutic avenues for keloid treatment.

A new process to improve short-chain fatty acids and bio-methane generation from waste activated sludge

As an important intermediate product, short-chain fatty acids（SCFAs） can be generated after hydrolysis and acidification from waste activated sludge, and then can be transformed to methane during anaerobic digestion process. In order to obtain more SCFA and methane,most studies in literatures were centered on enhancing the hydrolysis of sludge anaerobic digestion which was proved as un-efficient. Though the alkaline pretreatment in our previous study increased both the hydrolysis and acidification processes, it had a vast chemical cost which was considered uneconomical. In this paper, a low energy consumption pretreatment method, i.e. enhanced the whole three stages of the anaerobic fermentation processes at the same time, was reported, by which hydrolysis and acidification were both enhanced, and the SCFA and methane generation can be significantly improved with a small quantity of chemical input. Firstly, the effect of different pretreated temperatures and pretreatment time on sludge hydrolyzation was compared. It was found that sludge pretreated at 100°C for 60 min can achieve the maximal hydrolyzation. Further, effects of different initial p Hs on acidification of the thermal pretreated sludge were investigated and the highest SCFA was observed at initial p H 9.0with fermentation time of 6 d, the production of which was 348.63 mg COD/g VSS（6.8 times higher than the blank test） and the acetic acid was dominant acid. Then, the mechanisms for this new pretreatment significantly improving SCFA production were discussed. Finally,the effect of this low energy consumption pretreatment on methane generation was investigated.

Impact of undissociated volatile fatty acids on acidogenesis in a two-phase anaerobic system

This study investigated the degradation and production of volatile fatty acids（VFAs）in the acidogenic phase reactor of a two-phase anaerobic system.20 mmol/L bromoethanesulfonic acid（BESA）was used to inhibit acidogenic methanogens（which were present in the acidogenic phase reactor）from degrading VFAs.The impact of undissociated volatile fatty acids（un VFAs）on＂net＂VFAs production in the acidogenic phase reactor was then evaluated,with the exclusion of concurrent VFAs degradation.＂Net＂VFAs production from glucose degradation was partially inhibited at high un VFAs concentrations,with 59%,37% and 60% reduction in production rates at 2190 mg chemical oxygen demand（COD）/L undissociated acetic acid（un HAc）,2130 mg COD/L undissociated propionic acid（un HPr）and 2280 mg COD/L undissociated n-butyric acid（un HBu）,respectively.The profile of VFAs produced further indicated that while an un VFA can primarily affect its own formation,there were also un VFAs that affected the formation of other VFAs.