Bioinformatics analysis for the identification of Sprouty-related EVH1 domain-containing protein 3 expression and its clinical significance in thyroid carcinoma.

The poorly differentiated thyroid carcinoma (THCA) subtype is associated with an aggressive disease course, a less favorable overall prognosis, and an increased risk of distant organ metastasis. In this study, our objective was to explore the potential utility of the Sprouty-related EVH1 domain-containing protein 3 (SPRED3) as a biomarker for early diagnosis and prognosis in THCA patients. The differentially expressed prognostic-related genes associated with THCA were identified by querying The Cancer Genome Atlas (TCGA) database. The difference in the expression of the SPRED3 gene between thyroid carcinoma (THCA) tissues and normal tissues was analyzed using data from The Cancer Genome Atlas (TCGA) and further validated through immunohistochemistry. Univariate and multivariate Cox regression models were used, along with clinical information from THCA patients, to analyze the prognostic value of the SPRED3 gene in THCA patients. Functional enrichment analysis was subsequently performed to elucidate the molecular mechanisms underlying the regulatory effects of the SPRED3 gene on thyroid carcinoma. Additionally, we calculated the percentage of infiltrating immune cells in THCA patients and evaluated their correlation with SPRED3 gene expression. Compared with those in noncancerous thyroid tissue, the gene and protein expression levels of SPRED3 were found to be elevated in thyroid carcinoma tissues. Furthermore, the expression of SPRED3 in thyroid carcinoma exhibited significant correlations with tumor location, histological grade, pathological stage, and tumor node metastasis classification (TNM) stage. Univariate and multivariate Cox proportional hazards (Cox) regression analyses demonstrated that SPRED3 could serve as an independent prognostic factor for predicting the overall survival of THCA patients. The results of functional enrichment analysis suggested the potential involvement of SPRED3 in the regulation of extracellular matrix organization, epidermal development, signaling receptor activator activity, skin development, receptor ligand activity, glycosaminoglycan binding, neuroactive ligand‒receptor interaction, the IL-17 signaling pathway, and the PI3K-Akt signaling pathway. Additionally, there were significant correlations between the expression level of the SPRED3 gene and the infiltration of various immune cells (eosinophils, central memory T cells, neutrophils, macrophages, and NK cells) within the thyroid tumor microenvironment. SPRED3 can be used as a prognostic biomarker in patients with THCA could potentially be therapeutic target for THCA.

How to choose kinematic or mechanical alignment individually according to preoperative characteristics of patients?

BACKGROUND: Making decisions in alignment techniques in total knee arthroplasty (TKA) remains controversial. This study aims to identify the potential patients who were suitable for the kinematic (KA) or mechanical alignment (MA). METHODS: We reviewed 296 consecutive patients (296 TKAs, including 114 KA-TKAs and 182 MA-TKAs) who underwent unilateral TKA using a computer-assisted navigation from 2016 to 2018 in our prospectively maintained database. The minimum followup was 1 year. Clinical outcomes including the range of motion (ROM) and knee society score (KSS) were compared between KA-TKAs and MA-TKAs. Multiple regression models were used to evaluate the relationship between alignment techniques and KSS at the 1-year followup. Interaction and stratified analyses were conducted according to gender, age, body mass index (BMI), preoperative hip-knee-ankle (HKA) angle, ROM and KSS. RESULTS: ROM and KSS at the 1-year followup didn't differ between MA-TKAs and KA-TKAs (all p > 0.05). Alignment techniques did not associate with postoperative ROM (Adjusted ß = 0.4, 95% confidence interval [CI]: - 0.3, 1.6; p = 0.752) or 1-year KSS (Adjusted ß = 2.2, 95%CI: - 0.7, 5.6; p = 0.107). Patients with a BMI more than 30 kg/m^2 achieved better 1-year KSS when using MA than KA (p for interaction< 0.05). Additionally, patients with preoperative HKA angle more than 10 degrees varus benefited more from KA than MA (p for interaction< 0.05). CONCLUSIONS: Patients with severe varus deformity may be suitable for the KA technique, whereas MA should be used in obese patients.

Establishment of a rapid and effective plate chromogenic assay for screening of Aspergillus species with high ß-fructofuranosidase activity for fructooligosaccharides production.

Fructooligosaccharides (FOS) are commonly regarded as prebiotics and used as components of functional foods. Currently, the industrial sucrose-to-FOS biotransformation is mainly carried out using the microbial-derived ß-fructofuranosidases with transglycosylation activity as catalysts. Evaluation of the ability of a microorganism to produce ß-fructofuranosidase is commonly conducted by measuring enzyme activity. However, the traditional method requires several steps to identify strains with high ß-fructofuranosidase activity, which is not suitable for high-throughput screening. To facilitate screening of a large number of microbial cultures, this study developed a plate chromogenic assay method based on the glucose oxidase (GOD) - peroxidase (POD) bienzymatic system for screening of ß-fructofuranosidase-producing fungal strains and predicting their potential to produce FOS. This method used the amount of glucose released from sucrose as indicator to form clear pink halos around the microbial colonies with ß-fructofuranosidase activity. Cultivation conditions for the plate assay were optimized as cultivation time 5 h and spore inoculum concentration 108/ml. Moreover, the method was applied to screening of an Aspergillus niger ATCC 20611 mutant library. The mutant A11 displaying the largest pink halo was screened out and its ß-fructofuranosidase activity was determined to be 1.65 fold than that of the parental strain. Thin layer chromatography (TLC) assay further indicated that A11 with the largest halo possessed the highest FOS synthesis ability. These results demonstrated the potential of this plate chromogyenic assay method in the rapid and effective identification of excellent FOS producers from a large number of strain samples.

Association of PAR-2 Gene Polymorphisms with the Inflammatory Response and Susceptibility to Knee Osteoarthritis in the Chinese Han Population.

OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of protease-activated receptor 2 (PAR-2) and the susceptibility to knee osteoarthritis (KOA) and synovial expression of inflammatory factors in the Chinese Han population. METHODS: Three hundred fifty KOA patients (KOA group) and 345 healthy volunteers (control group) were recruited for the study. Five milliliters of venous blood was taken from each subject to detect the PAR-2 rs1529505, rs631465, and rs2242991 locus genotypes. The expression of PAR-2 mRNA in the synovial tissue and the levels of matrix metalloproteinase (MMP-1), MMP-9, interleukin (IL)-6, and IL-1ß in the joint effusion were detected in 205 KOA patients who had undergone joint replacement surgery. RESULTS: The PAR-2 rs1529505 T allele and the rs2242991 G allele carriers had a higher risk of KOA (p < 0.001). The severity of KOA in patients with the PAR-2 rs1529505 and rs2242991 mutations were higher than in the wild-type controls (p < 0.05). The expression levels of the PAR-2 mRNA in wild types, heterozygotes, and homozygotes of the rs1529505 and rs2242991 loci increased in turn (p < 0.001). The levels of MMP-1, MMP-9, IL-6, and IL-1ß in the synovial fluid of the PAR-2 rs1529505 and rs2242991 locus mutants were distinctly higher than those with the wild-type alleles (p < 0.01). There was no correlation between the rs631465 SNP and susceptibility to KOA, severity of KOA, nor levels of PAR-2 mRNA, MMP-1, MMP-9, IL-6, and IL-1ß. CONCLUSIONS: The PAR-2 SNPs rs1529505 and rs2242991 are associated with the susceptibility to KOA. KOA is more severe in patients harboring the T and G alleles of these two SNPs, respectively. The levels of inflammatory factors in synovial tissue and blood are higher than those in wild-type patients.