Cannabis through the looking glass: chemo- and enantio-selective separation of phytocannabinoids by enantioselective ultra high performance supercritical fluid chromatography

By using the Inverted Chirality Columns Approach (ICCA) we have developed an enantioselective UHPSFC method to determine the enantiomeric excess (ee) of (-)-Δ(9)-THC in medicinal marijuana (Bedrocan®). The ee was high (99.73%), but the concentration of the (+)-enantiomer (0.135%) was not negligible, and it is worth a systematic evaluation of bioactivity

Accumulation of trace metals in crayfish tissues: is Procambarus clarkii a vector of pollutants in Po Delta inland waters?

Concentrations of trace elements (Cd, Pb, As, Cu and Zn) were determined in superficial sediments and in hepatopancreas, exoskeleton, and abdominal muscle of the red swamp crayfish Procambarus clarkii from several canals of the Po River Delta area. Sediments of the studied canals exhibited some metal pollution. The hepatopancreas of the crayfish showed a higher concentration of trace metals in comparison to the other tissues at all sites under scrutiny. Concentrations of As and Pb, either in sediment and P. clarkii tissues, were probably related to the use of fertilizers and pesticides. Moreover, the levels of certain metals accumulated in the abdominal muscle (Pb, Cu and Zn) exceeded the threshold values considered harmful to human health. The Toxic Contamination Index, depending on the bioaccumulation data of hepatopancreas and abdominal muscle, allowed us to assess the toxicity by heavy metals of sediments measuring the stress level of the detoxification organ, and resulted in >1 only at two sampling canals. We hypothesize that P. clarkii in the Po River Delta aquatic communities can act as a vector of pollutants, as crayfish can transfer their relatively high amount of heavy metals to higher trophic levels

Functional characterization and transcriptional repression by Lacticaseibacillus paracasei DinJ-YafQ

DinJ-YafQ is a bacterial type II TA system formed by the toxin RNase YafQ and the antitoxin protein DinJ. The activity of YafQ and DinJ has been rigorously studied in Escherichia coli, but little has been reported about orthologous systems identified in different microorganisms. In this work, we report an in vitro and in vivo functional characterization of YafQ and DinJ identified in two different strains of Lacticaseibacillus paracasei and isolated as recombinant proteins. While DinJ is identical in both strains, the two YafQ orthologs differ only for the D72G substitution in the catalytic site. Both YafQ orthologs digest ribosomal RNA, albeit with different catalytic efficiencies, and their RNase activity is neutralized by DinJ. We further show that DinJ alone or in complex with YafQ can bind cooperatively to a 28-nt inverted repeat overlapping the -35 element of the TA operon promoter. Atomic force microscopy imaging of DinJ-YafQ in complex with DNA harboring the cognate site reveals the formation of different oligomeric states that prevent the binding of RNA polymerase to the promoter. A single amino acid substitution (R13A) within the RHH DNA-binding motif of DinJ is sufficient to abolish DinJ and DinJ-YafQ DNA binding in vitro. In vivo experiments confirm the negative regulation of the TA promoter by DinJ and DinJ-YafQ and unveil an unexpected high expression-related toxicity of the gfp reporter gene. A model for the binding of two YafQ-(DinJ)2-YafQ tetramers to the promoter inverted repeat showing the absence of protein-protein steric clash is also presented. KEY POINTS: • The RNase activity of L. paracasei YafQ toxin is neutralized by DinJ antitoxin. • DinJ and DinJ-YafQ bind to an inverted repeat to repress their own promoter. • The R13A mutation of DinJ abolishes DNA binding of both DinJ and DinJ-YafQ

Efficient Radiative Pumping of Polaritons in a Strongly Coupled Microcavity by a Fluorescent Molecular Dye

KGaA, Weinheim.The optical properties of a series of strongly coupled microcavities containing the fluorescent molecular dye BODIPY-Br (bromine-substituted boron-dipyrromethene) dispersed into a transparent dielectric matrix are explored, with each cavity having a different exciton-photon detuning. Using temperature dependent emission, time-resolved spectroscopy, white-light reflectivity, and measurements of fluorescence quantum yield, the population of polaritons is explored along the lower polariton branch. It is found that both the cavity fluorescence quantum efficiency and the distribution of polariton states along the lower polariton branch is a function of exciton-photon detuning. Importantly, it is shown that in the most negatively detuned cavities, the emission quantum efficiency approaches that of a control (noncavity) film. A simple fitting model is developed, which is based upon direct radiative pumping of polariton states along the lower polariton branch and used it to obtain an excellent agreement with measured photoluminescence as a function of temperature and exciton-photon detuning, and qualitative agreement with the measured photoluminescence quantum efficiency. The radiative pumping mechanism indicates that to facilitate the formation of a nonequilibrium polariton condensate in strongly-coupled microcavities containing dispersed molecular dyes, it is important to utilize materials having high fluorescent quantum efficiency and fast radiative rates

Sustainability in peptide chemistry: current synthesis and purification technologies and future challenges.

Developing greener synthesis processes is an inescapable necessity to transform the industrial landscape, mainly in the pharmaceutical sector, into a long-term, sustainable reality. In this context, the renaissance of peptides as medical treatments, and the enforcement of more stringent sustainability requirements by regulatory agencies, pushed chemists toward the introduction of sustainable processes to prepare highly pure, active pharmaceutical ingredients (APIs). Innovative upstream (synthesis) and downstream (purification) methodologies have been developed during the last 5 years with the introduction and optimization of several technologies in solid-phase peptide synthesis (SPPS), liquid-phase peptide synthesis (LPPS), chemoenzymatic peptide synthesis (CEPS), and chromatographic procedures. These innovations are also moving toward the introduction of continuous processes that represent one of the most important targets for iterative processes. This overview discusses the most recent efforts in making peptide chemistry greener. The extensive studies that were carried out on green solvents, reaction conditions, auxiliary reagents and purification technologies in the peptide segment can be useful to other fields of organic synthesi

Static pressure recovery analysis in the vane island diffuser of a centrifugal pump

The overall performance of a vane-island type diffuser of a centrifugal pump model was obtained by means of directional probe traverses. These measurements were performed in an air model of a real hydraulic pump for five volume flow rates. Directional probe traverses are performed with a classical three-hole probe to cover most of the complete inlet section of the diffuser from hub to shroud and from pressure to suction side. Existing Particle image velocimetry (PIV) measurement results are also used to compare probe measurement results between the inlet and outlet throats of vane island diffuser at mid-span. Some assistance from already existing unsteady calculation, including leakage effects, is used to evaluate the numerical approach capability and to correctly define the mean initial conditions at impeller’s outlet section. Pressure recovery and the measured total pressure loss levels inside this particular vane diffuser geometry are then calculated. Detailed analysis of the flow structure at the inlet section of the vane island diffuser is presented to focus on pressure evolution inside the entire diffuser section for different flow rates. The combined effects of incidence angle and blockage distributions along hub to shroud direction are found to play an important role on loss distribution in such a diffuser

HER2 expression and efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients

No data are available on the role of HER2 overexpression in predicting the efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients. We retrospectively evaluated this role in patients enrolled in a phase III study comparing standard FEC21 (5-fluorouracil, epirubicin, and cyclophosphamide, administered every 3 weeks) vs dose-dense FEC14 (the same regimen repeated every 2 weeks). HER2 status was determined for 731 of 1214 patients. Statistical analyses were performed to test for interaction between treatment and HER2 status with respect to event-free survival (EFS) and overall survival (OS); EFS and OS were compared within each HER2 subgroup and within each treatment arm. Median follow-up was 6.7 years. Among FEC21-treated patients, both EFS (HR=2.07; 95% CI 1.27–3.38) and OS (HR=2.47; 95% CI 1.34–4.57) were significantly worse in HER2 + patients than in HER2 − patients. Among FEC14-treated patients, differences in either EFS (HR=1.21; 95% CI 0.65–2.24) or OS (HR=1.85; 95% CI 0.88–3.89) between HER2 + and HER2 − patients were not statistically significant. Interaction analysis suggested that the use of dose-dense FEC14 might remove the negative prognostic effect of HER2 overexpression on EFS and OS. Our data suggest a potential role of HER-2 overexpression in predicting the efficacy of dose-dense epirubicin-containing chemotherapy and the need to confirm this hypothesis in future prospective studies

Ectopic thymoma simulating a pericardial cyst

We present a case of a 53 year old man with a thymoma near the pericardium, a rare ectopic localisation of thymoma. A round radiodensity found at the right cardiophrenic angle was initially suspected at the echocardiography to be a pericardial cyst. The diagnosis of thymoma was made only after histopathological examination of the surgically re-sected lesion

Rotation of nilotinib and imatinib for first-line treatment of chronic phase chronic myeloid leukemia.

he introduction of second-generation tyrosine-kinase inhibitors (TKIs) has generated a lively debate on the choice of first-line TKI in chronic phase, chronic myeloid leukemia (CML). Despite the TKIs have different efficacy and toxicity profiles, the planned use of two TKIs has never been investigated. We report on a phase 2 study that was designed to evaluate efficacy and safety of a treatment alternating nilotinib and imatinib, in newly diagnosed BCR-ABL1 positive, chronic phase, CML patients. One hundred twenty-three patients were enrolled. Median age was 56 years. The probabilities of achieving a complete cytogenetic response, a major molecular response, and a deep molecular response (MR 4.0) by 2 years were 93%, 87%, and 61%, respectively. The 5-year overall survival and progression-free survival were 89%. Response rates and survival are in the range of those reported with nilotinib alone. Moreover, we observed a relatively low rate of cardiovascular adverse events (5%). These data show that the different efficacy and toxicity profiles of TKIs could be favorably exploited by alternating their us