Search

Abstract Chimeric antigen receptor T (CAR-T) cell therapy has greatly improved the prognosis of relapsed and refractory patients with large B-cell lymphoma (LBCL). Early identification and intervention of patients who may respond poorly to CAR-T cell therapy will help to improve the efficacy. Ninety patients from a Chinese cohort who received CAR-T cell therapy and underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans at the screening stage (median time to infusion 53.5 days, range 27–176 days), 1 month and 3 months after CAR-T cell infusion were analyzed, with RNA-sequencing conducted on 47 patients at the screening stage. Patients with maximum diameter of the largest lesion (Dmax)

Objective[18F]Fluorocholine positron emission tomography/computed tomography (PET/CT) is used frequently in addition to [99mTc]Tc-Sestamibi scintigraphy and ultrasonography for the location of hyperfunctioning parathyroid glands. The aim of this study is to evaluate the performance of quantitative criteria in [18F]fluorocholine PET/CT for localization of hyperfunctioning parathyroid glands. The secondary objective is to highlight a correlation between the detection rate of [18F]fluorocholine PET/CT and serum parathyroid hormone (PTH) level.Materials and methodsIn two academic centers, we retrospectively included patients with biological hyperparathyroidism (HPT) and who had [18F]fluorocholine PET/CT. After a visual analysis, to measure the overall performance of [18F]fluorocholine PET/CT, a blind reading was carried out with standardized measurements of maximum standardized uptake value (SUVmax), liver ratio, thyroid ratio, and size ratio. We analyzed the quantitative criteria of [18F]fluorocholine PET/CT compared to the histological results, in particular to identify differences between adenomas and hyperplasias. We compared the performance of each quantitative criterion to the overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [18F]fluorocholine PET/CT. The detection rate of hyperfunctioning parathyroid glands was calculated in subgroups of serum PTH level.ResultsThe quantitative criteria in [18F]fluorocholine PET/CT were measured for 120 patients (135 lesions). The areas under the receiver operating characteristic (ROC) curve representing SUVmax and liver ratio were significantly increased. The optimal cut-off values represented by the maximum Youden index was >4.12 for SUVmax and >27.4 for liver ratio. Beyond certain threshold values of SUVmax (>4.12) or liver ratio (>38.1), all the lesions were histologically proven adenomas. SUVmax and liver ratio were significantly higher for adenomas than for hyperplasias and differential diagnosis (p = 0.0085 and p = 0.0002). The positivity of [18F]fluorocholine PET/CT was correlated with PTH level. Detection rates were 55.56, 75.56, and 87.5%, respectively, for serum PTH < 70, 70 to 120, and >120 ng/ml.ConclusionSemi-quantitative measurements (SUVmax and liver ratio) should be considered as additional tools in interpretation of [18F]fluorocholine PET/CT. These quantitative parameters have lower overall performance but higher specificity than overall visual analysis in identifying an adenoma. Above certain threshold values, all lesions are adenomas. [18F]fluorocholine PET/CT confirms excellent performance for the detection of hyperfunctional parathyroids. For serum PTH levels < 70 ng/ml, the detection rate of [18F]fluorocholine PET/CT is strongly decreased.

Lignin in plant biomass represents a target for engineering strategies towards the development of a sustainable bioeconomy. In addition to the conventional lignin monomers, namely p-coumaryl, coniferyl and sinapyl alcohols, tricin has been shown to be part of the native lignin polymer in certain monocot species. Because tricin is considered to initiate the polymerization of lignin chains, elucidating its biosynthesis and mechanism of export to the cell wall constitute novel challenges for the engineering of bioenergy crops. Late steps of tricin biosynthesis require two methylation reactions involving the pathway intermediate selgin. It has recently been demonstrated in rice and maize that caffeate O-methyltransferase (COMT) involved in the synthesis syringyl (S) lignin units derived from sinapyl alcohol also participates in the synthesis of tricin in planta. In this work, we validate in sorghum (Sorghum bicolor L.) that the O-methyltransferase responsible for the production of S lignin units (SbCOMT / Bmr12) is also involved in the synthesis of lignin-linked tricin. In particular, we show that biomass from the sorghum bmr12 mutant contains lower level of tricin incorporated into lignin, and that SbCOMT can methylate the tricin precursors luteolin and selgin. Our genetic and biochemical data point toward a general mechanism whereby COMT is involved in the synthesis of both tricin and S lignin units.

The expression of recombinant hemagglutinin in plants is a promising alternative to the current egg-based production system for the influenza vaccines. Protein-stabilizing fusion partners have been developed to overcome the low production yields and the high downstream process costs associated with the plant expression system. In this context, we tested the fusion of hydrophobin I to the hemagglutinin ectodomain of the influenza A (H1N1)pdm09 virus controlled by the hybrid En2PMA4 transcriptional promoter to rapidly produce high levels of recombinant antigen by transient expression in agro-infiltrated Nicotiana benthamiana leaves. The fusion increased the expression level by a factor of ∼ 2.5 compared to the unfused protein allowing a high accumulation level of 8.6% of the total soluble proteins. Hemagglutinin was located in ER-derived protein bodies and was successfully purified by combining an aqueous-two phase partition system and a salting out step. Hydrophobin interactions allowed the formation of high molecular weight hemagglutinin structures, while unfused proteins were produced as monomers. Purified protein was shown to be biologically active and to induce neutralizing antibodies after mice immunization. Hydrophobin fusion to influenza hemagglutinin might therefore be a promising approach for rapid, easy, and low cost production of seasonal or pandemic influenza vaccines in plants.