Study on Extraction and Properties of Gelatin from Squid Skin

A kind of aquatic gelatin was prepared from squid skin. The technological parameters for extracting gelatin were optimized by the method of orthogonal design. The fundamental properties of the raw material and gelatin were analyzed. The results showed that the optimal extraction conditions were as follows： pH val- ue of 8, temperature at 70 ℃, material-to-liquid ratio at 1：4, and extraction time of 1.5 h. under such conditions, the highest yield of gelatin and the purity were 5.94% and 96.73%, respectively. The physicoehemical properties of squid skin gelatin were coincided with standards of edible gelatin. In addition, the contents of amino acids were similar to many kinds of aquatic gelatin.

SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation

Background:Liver cancer is a malignancy with high morbidity and mortality rates.Serpin family E member 2(SERPINE2)has been reported to play a key role in the metastasis of many tumors.In this study,we aimed to investigate the potential mechanism of SERPINE2 in liver cancer metastasis.Methods:The Cancer Genome Atlas database(TCGA),including DNA methy-lation and transcriptome sequencing data,was utilized to identify the crucial oncogene associated with DNA methylation and cancer progression in liver can-cer.Data from the TCGA and RNA sequencing for 94 pairs of liver cancer tissues were used to explore the correlation between SERPINE2 expression and clin-ical parameters of patients.DNA methylation sequencing was used to detect the DNA methylation levels in liver cancer tissues and cells.RNA sequencing,cytokine assays,immunoprecipitation(IP)and mass spectrometry(MS)assays,protein stability assays,and ubiquitination assays were performed to explore the regulatory mechanism of SERPINE2 in liver cancer metastasis.Patient-derived xenografts and tumor organoid models were established to determine the role of SERPINE2 in the treatment of liver cancer using sorafenib.Results:Based on the public database screening,SERPINE2 was identified as a tumor promoter regulated by DNA methylation.SERPINE2 expression was significantly higher in liver cancer tissues and was associated with the dismal prognosis in patients with liver cancer.SERPINE2 promoted liver cancer metas-tasis by enhancing cell pseudopodia formation,cell adhesion,cancer-associated fibroblast activation,extracellular matrix remodeling,and angiogenesis.IP/MS assays confirmed that SERPINE2 activated epidermal growth factor receptor(EGFR)and its downstream signaling pathways by interacting with EGFR.Mechanistically,SERPINE2 inhibited EGFR ubiquitination and maintained its protein stability by competing with the E3 ubiquitin ligase,c-Cbl.Additionally,EGFR was activated in liver cancer cells after sorafenib treatment,and SER-PINE2 knockdown-induced EGFR downregulation significantly enhanced the therapeutic efficacy of sorafenib against liver cancer.Furthermore,we found that SERPINE2 knockdown also had a sensitizing effect on lenvatinib treatment.Conclusions:SERPINE2 promoted liver cancer metastasis by preventing EGFR degradation via c-Cbl-mediated ubiquitination,suggesting that inhibition of the SERPINE2-EGFR axis may be a potential target for liver cancer treatment.

Effects of sulfur on variations in the chemical speciation of heavy metals from fly ash glass

This work designed a new CaO-Al_(2)O_(3)-SiO_(2)-SO3 glass for the immobilization of multiple heavy metals found in dechlorinated fly ash having high amounts of calcium and sulfur. Increasing the (CaO + SO3)/SiO_(2) mass ratio (M(CS/S)) from 0.28 to 0.85 was found to lower the proportions of Mn, Ni and Zn in an unstable state, while an M(CS/S) ratio of 0.51 gave the lowest proportions of unstable Cr and Pb. Decreasing the degree of polymerization of the glassy network increased the proportions of Mn, Cr, Ni, Pb and Zn in the carbonate bound state. The leaching out of metals in this state was the primary cause of degradation of Q^(3) structural units in the glassy network. The amount of Mn in the iron-manganese oxide bound state was increased by increasing the number of Q^(2) units in the silicate network. Decreasing the CaO/SiO_(2) mass ratio (M(C/S)) raised the proportions of Mn, Ni and Zn in the unstable state. An M(C/S) value of 0.43 lowered the proportions of unstable Cr and Pb. A principal components analysis determined that the leaching of toxic heavy metals from the glass was primarily related to the proportions of these metals in the unstable state while there were no evident correlations between leaching and the proportions in stable states.

Culture of patient-derived multicellular clusters in suspended hydrogel capsules for pre-clinical personalized drug screening

A personalized medication regimen provides precise treatment for an individual and can be guided by pre-clinical drug screening.The economical and high-efficiency simulation of the liver tumor microenvironment(TME)in a drug-screening model has high value yet challenging to accomplish.Herein,we propose a simulation of the liver TME with suspended alginate-gelatin hydrogel capsules encapsulating patient-derived liver tumor multicellular clusters,and the culture of patient-derived tumor organoids(PDTOs)for personalized pre-clinical drug screening.The hydrogel capsule offers a 3D matrix environment with mechanical and biological properties similar to those of the liver in vivo.As a result,18 of the 28 patient-derived multicellular clusters were successfully cultured as PDTOs.These PDTOs,along with hepatocyte growth factor(HGF)of non-cellular components,preserve stromal cells,including cancer-associated fibroblasts(CAFs)and vascular endothelial cells(VECs).They also maintain stable expression of molecular markers and tumor heterogeneity similar to those of the original liver tumors.Drugs,including cabazitaxel,oxaliplatin,and sorafenib,were tested in PDTOs.The sensitivity of PDTOs to these drugs differs between individuals.The sensitivity of one PDTO to oxaliplatin was validated using magnetic resonance imaging(MRI)and biochemical tests after oxaliplatin clinical treatment of the corresponding patient.Therefore,this approach is promising for economical,accurate,and high-throughput drug screening for personalized treatment.