The PAX8/PPARgamma (PPFP) fusion-oncogene is moderately specific for follicular thyroid carcinomas (FTC). It remains unknown whether this can be translated into improved diagnosis, classification, or outcome prediction. We studied a cohort of well-characterized follicular adenomas (FA), FTC, and Hurthle cell carcinomas (HCC) from patients with complete clinical follow-up, to determine whether PPARgamma immunohistochemistry (as a surrogate of PAX8/PPARgamma expression) helps to distinguish FA from FTC and to assess its diagnostic accuracy as an adjunct to frozen section. We also correlated PPARgamma staining with clinical outcomes to assess its role as a prognostic marker.PPARgamma staining was more common in FTC (31 of 54; 57%) than in HCC (one of 23; 4%) or FA (four of 31; 13%) (P < 0.000001). Adjunctive use of PPARgamma immunohistochemistry improved diagnostic sensitivity of intraoperative frozen section from 84% to 96% (P < 0.05) but reduced specificity from 100% to 90% (P < 0.05). PPARgamma staining was associated with favorable prognostic indicators (female gender, better tumor differentiation, and lesser risk of metastases).PPARgamma staining may be helpful in the differential diagnosis of FA, FTC, and HCC, particularly when diagnostic sensitivity of histomorphology is reduced (e.g. during intraoperative frozen section). PPARgamma staining also shows an association with favorable prognosis and may have a role in risk stratification.

Resveratrol, a plant-derived polyphenolic compound with various health activities, is widely used in nutraceutical and food additives. Herein, combinatorial optimization of resveratrol biosynthetic pathway and intracellular environment of E. coli was carried out. By screening pathway genes from various species and exploring their expression pattern, we initially constructed resveratrol-producing strains. Further targeting at availability of malonyl-CoA through expressing ACC of Corynebacterium glutamicum and antisense inhibiting native fabD significantly increased resveratrol biosynthesis. Transport engineering for resveratrol secretion and molecular chaperones helping for folding heterologous enzymes were employed to improve the intracellular environments in remarkable degrees. By introducing PcTAL of Phanerochaete chrysosporium and tuning expression model of PcTAL, At4CL, and VvSTS, an engineered E. coli produced 57.77 mg/L of resveratrol from L-tyrosine. After integrating the above strategies, resveratrol titer reached to 238.71 mg/L from L-tyrosine. The combinatorial optimization in this study provides a promising strategy to produce valuable natural products in heterologous expression systems.

SummaryIn this study, we evaluated the prognostic value of plasma galectin-3 levels in patients with coronary heart disease (CHD) and chronic heart failure (HF) and selected 261 CHD patients who were consecutively admitted to our hospital. The enrolled chronic HF patients included HF patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). Patients without HF served as the control group. Galectin-3 and B-type natriuretic peptide (BNP) levels were determined and the primary endpoint was the composite of all-cause mortality and rehospitalization with 12-month follow-up. Plasma galectin-3 levels were higher in HF patients compared with non-HF patients (P < 0.001). Receiver operating characteristic (ROC) analyses for diagnosis of HF showed that galectin-3 had the greatest area under the curve (AUC) of 0.756 (P < 0.001), with an optimal cutoff of 10.8 ng/mL, yielding a sensitivity of 81.7% and a specificity of 61.7%. Follow-up ROC analyses of galectin-3 for outcome prediction showed an optimal cutoff of 17.8 ng/ mL, yielding a sensitivity of 97.3% and a specificity of 77.6%. Galectin-3 yielded an AUC of 0.899 (P < 0.001), whereas the AUC of BNP was 0.633 (P = 0.022). Galectin-3 led to an AUC of 0.931 (P < 0.001) for HFpEF and an AUC of 0.882 (P < 0.001) for HFrEF. Cox proportional hazards regression analysis revealed that galectin-3 was an independent prognostic predictor for chronic HF, especially for HFpEF patients (RR: 1.231, 95% CI: 1.066-1.442). In summary, plasma galectin-3 levels were increased in CHD HF patients and were an independent predictor of all-cause mortality and rehospitalization. In HFpEF patients galectin-3 levels correlated stronger with outcomes than in HFrEF patients. (Int Heart J 2015; 56: 314-318)

Background4-Hydroxymandelic acid (4-HMA) is a valuable aromatic fine chemical and widely used for production of pharmaceuticals and food additives. 4-HMA is conventionally synthesized by chemical condensation of glyoxylic acid with excessive phenol, and the process is environmentally unfriendly. Microbial cell factory would be an attractive approach for 4-HMA production from renewable and sustainable resources.ResultsIn this study, a biosynthetic pathway for 4-HMA production was constructed by heterologously expressing the fully synthetic 4-hydroxymandelic acid synthase (shmaS) in our l-tyrosine-overproducing Escherichia coli BKT5. The expression level of shmaS was optimized to improve 4-HMA production by fine tuning of four promoters of different strength combined with three plasmids of different copy number. Furthermore, two genes aspC and tyrB in the competitive pathway were deleted to block the formation of byproduct to enhance 4-HMA biosynthesis. The final engineered E. coli strain HMA15 utilized glucose and xylose simultaneously and produced 15.8 g/L of 4-HMA by fed-batch fermentation in 60 h.ConclusionsMetabolically engineered E. coli strain for 4-HMA production was designed and constructed, and efficiently co-fermented glucose and xylose, the major components in the hydrolysate mixture of agricultural biomass. Our research provided a promising biomanufacturing route to produce 4-HMA from lignocellulosic biomass.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-016-0489-4) contains supplementary material, which is available to authorized users.