Beyond Benzoin Condensation: Trimerization of Aldehydes via Metal-Free Aerobic Oxidative Esterification of Aldehydes with Benzoin Products in the Presence of Cyanide

An unusual trimerization of aldehydes in the presence of cyanide via metal-free aerobic oxidative esterification under ambient conditions is described. Various aromatic aldehydes provided the corresponding oxidative esterification products in good to excellent yields. Mechanistic studies suggested that this reaction would proceed via a two-step sequence: cyanide-catalyzed benzoin condensation of aldehydes and subsequent aerobic oxidative esterification of aldehydes with the resultant benzoin products. The usefulness of this protocol was further demonstrated by converting the resulting trimeric products into other biologically important compounds

Accuracy of the Fluorescence-Activated Cell Sorting Assay for the Aquaporin-4 Antibody (AQP4-Ab): Comparison with the Commercial AQP4-Ab Assay Kit

<div><p>Background</p><p>The aquaporin-4 antibody (AQP4-Ab) is a disease-specific autoantibody to neuromyelitis optica (NMO). We aimed to evaluate the accuracy of the FACS assay in detecting the AQP4-Ab compared with the commercial cell-based assay (C-CBA) kit.</p><p>Methods</p><p>Human embryonic kidney-293 cells were transfected with human aquaporin-4 (M23) cDNA. The optimal cut off values of FACS assay was tested using 1123 serum samples from patients with clinically definite NMO, those at high risk for NMO, patients with multiple sclerosis, patients with other idiopathic inflammatory demyelinating diseases, and negative controls. The accuracy of FACS assay and C-CBA were compared in consecutive 225 samples that were collected between January 2014 and June 2014.</p><p>Results</p><p>With a cut-off value of MFIi of 3.5 and MFIr of 2.0, the receiver operating characteristic curve for the FACS assay showed an area under the curve of 0.876. Among 225 consecutive sera, the FACS assay and C-CBA had a sensitivity of 77.3% and 69.7%, respectively, in differentiating the sera of definite NMO patients from sera of controls without IDD or of MS. Both assay had a good specificity of 100% in it. The overall positivity of the C-CBA among FACS-positive sera was 81.5%; moreover, its positivity was low as 50% among FACS-positive sera with relatively low MFIis.</p><p>Conclusions</p><p>Both the FACS assay and C-CBA are sensitive and highly specific assays in detecting AQP4-Ab. However, in some sera with relatively low antibody titer, FACS-assay can be a more sensitive assay option. In real practice, complementary use of FACS assay and C-CBA will benefit the diagnosis of NMO patients, because the former can be more sensitive among low titer sera and the latter are easier to use therefore can be widely used.</p></div

Results of the commercial cell-based assay kit according to the FACS assay grouped by mean fluorescence intensity index titer.

<p>Results of the commercial cell-based assay kit according to the FACS assay grouped by mean fluorescence intensity index titer.</p

Comparison of the FACS assay with the commercial cell-based assay kit in diverse disease group.

<p>Comparison of the FACS assay with the commercial cell-based assay kit in diverse disease group.</p

Results of the ROC analysis.

<p>The ROC analysis showed that the MFIis for the FACS revealed an area under the curve of 0.876 when detecting sera from patients with definite NMO. Abbreviations: FACS = fluorescence-activated cell sorting, MFIi = mean fluorescence intensity index, NMO = neuromyelitis optica, ROC = receiver operating characteristic.</p

Flow chart illustrating the process of subject selection and analysis.

<p>For the analysis of the accuracy of the FACS assay, all 1123 serum samples were used. To compare the accuracy of the FACS assay with the C-CBA kit, 225 serum samples (54 FACS-positive, 6 FACS-borderline, and 165 FACS-negative) were used. These 225 samples were further classified into groups 1–5 according to the MFIi of the FACS assay: Group 1 = AQP-4 Ab positive sera with high titer of MFIi (≥ 50), Group 2 = AQP-4 Ab positive sera with medium titer of MFIi (10 ≤ MFIi < 50), Group 3 = AQP-4 Ab positive sera with low titer of MFIi (3.5 ≤ MFIi < 10), Group 4 = sera with borderline MFIi (2 ≤ MFIi < 3.5), Group 5 = AQP-4 Ab negative sera (MFI < 2). MFIi values were considered to be significant only when the MFI ratio is ≥2). The researchers who performed the C-CBA were blind to the results of the FACS assay. Abbreviations: AQP4-Ab = aquaporin-4 antibody, C-CBA = commercial cell-based assay, FACS = fluorescence-activated cell sorting, FACS-positive = tested positive in the FACS assay, FACS-negative = tested negative in the FACS assay, FACS-borderline = tested borderline in the FACS assay, IIDD = idiopathic inflammatory demyelinating disease, MFIi = mean fluorescence intensity index.</p

Number of AQP4-Ab-positive serum samples in each diagnostic group according to the mean fluorescence intensity index cut-off values.

<p>Number of AQP4-Ab-positive serum samples in each diagnostic group according to the mean fluorescence intensity index cut-off values.</p

Examples of the FACS data.

<p>The FACS data for healthy control, positive control with diverse dilution concentrations, and positive test results are shown.</p

<i>In Silico Oncology</i>: Quantification of the <i>In Vivo</i> Antitumor Efficacy of Cisplatin-Based Doublet Therapy in Non-Small Cell Lung Cancer (NSCLC) through a Multiscale Mechanistic Model

<div><p>The 5-year survival of non-small cell lung cancer patients can be as low as 1% in advanced stages. For patients with resectable disease, the successful choice of preoperative chemotherapy is critical to eliminate micrometastasis and improve operability. <i>In silico</i> experimentations can suggest the optimal treatment protocol for each patient based on their own multiscale data. A determinant for reliable predictions is the a priori estimation of the drugs’ cytotoxic efficacy on cancer cells for a given treatment. In the present work a mechanistic model of cancer response to treatment is applied for the estimation of a plausible value range of the cell killing efficacy of various cisplatin-based doublet regimens. Among others, the model incorporates the cancer related mechanism of uncontrolled proliferation, population heterogeneity, hypoxia and treatment resistance. The methodology is based on the provision of tumor volumetric data at two time points, before and after or during treatment. It takes into account the effect of tumor microenvironment and cell repopulation on treatment outcome. A thorough sensitivity analysis based on one-factor-at-a-time and latin hypercube sampling/partial rank correlation coefficient approaches has established the volume growth rate and the growth fraction at diagnosis as key features for more accurate estimates. The methodology is applied on the retrospective data of thirteen patients with non-small cell lung cancer who received cisplatin in combination with gemcitabine, vinorelbine or docetaxel in the neoadjuvant context. The selection of model input values has been guided by a comprehensive literature survey on cancer-specific proliferation kinetics. The latin hypercube sampling has been recruited to compensate for patient-specific uncertainties. Concluding, the present work provides a quantitative framework for the estimation of the <i>in-vivo</i> cell-killing ability of various chemotherapies. Correlation studies of such estimates with the molecular profile of patients could serve as a basis for reliable personalized predictions.</p></div

PRCC results.

<p>PRCC results.</p