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Malaria control programs on the Guiana Shield, a region of South America, are challenged by migrant populations looking for gold. Since 2008, the 'Harpie' operation to control and reduce illegal [...]

Background: In addition to their great optical properties, nanodiamonds (NDs) have recently proved useful for two-photon-excited photodynamic therapy (TPE-PDT) applications. Indeed, they are able to produce reactive oxygen species (ROS) directly upon two-photon excitation but not with one-photon excitation; Methods: Fluorescent NDs (FNDs) with a 100 nm diameter and detonation NDs (DNDs) of 30 nm were compared. In order to use the gems for cancer-cell theranostics, they were encapsulated in a bis(triethoxysilyl)ethylene-based (ENE) periodic mesoporous organosilica (PMO) shell, and the surface of the formed nanoparticles (NPs) was modified by the direct grafting of polyethylene glycol (PEG) and amino groups using PEG-hexyltriethoxysilane and aminoundecyltriethoxysilane during the sol–gel process. The NPs' phototoxicity and interaction with MDA-MB-231 breast cancer cells were evaluated afterwards; Results: Transmission electronic microscopy images showed the formation of core–shell NPs. Infrared spectra and zeta-potential measurements confirmed the grafting of PEG and NH2 groups. The encapsulation of the NDs allowed for the imaging of cancer cells with NDs and for the performance of TPE-PDT of MDA-MB-231 cancer cells with significant mortality. Conclusions: Multifunctional ND@PMO core–shell nanosystems were successfully prepared. The NPs demonstrated high biocompatibility and TPE-PDT efficiency in vitro in the cancer cell model. Such systems hold good potential for two-photon-excited PDT applications. [ABSTRACT FROM AUTHOR]

The psychosocial safety climate (PSC) reflects workers’ perceptions of senior management’s concern for mental health. Because the COVID-19 pandemic has exacerbated organizational issues, PSC could be a target for interventions attempting to preserve both the psychological health of employees and the economic health of companies. This study examines the direct and indirect relationships between PSC and work performance through two indicators of psychological health, psychological distress and post-traumatic growth, during a health crisis, i.e., prior to the second confinement in France. To this end, 2,004 participants from the French workforce completed a survey in October 2020. The results of mediation analyses indicate that PSC has a direct and positive influence on post-traumatic growth (PTG) and performance, as well as a direct negative influence on psychological distress. PSC also has an indirect positive influence on performance via psychological distress. Organizations that wish to jointly address mental health and performance at work would benefit from optimizing PSC. [ABSTRACT FROM AUTHOR]

To the Editor: French Guiana, an overseas territory of France and part of the European Union, is located on the northeast coast of South America (Figure). During 20082014, the number [...]

The synthesis, characterization and study of optical properties of innovative tetrafunctionalized zinc(II) porphyrins with carbonic anhydrase (CA) inhibitors in sulfonamide and coumarin series are described. The synthetic methodology relies on the preparation of the porphyrin core by condensation of azido triethyleneglycol functionalized benzaldehyde derivative with pyrrole followed by its metalation and inhibitors coupling via Huisgen click‐reaction. The tetrafunctionalized zinc(II) porphyrin with coumarin moieties showed selective inhibition against tumour‐associated hCA IX and hCA XII versus the cytosolic off‐targets hCA I and hCA II. This compound was able to accumulate on cell membrane and to impair pancreas cancer cells (Capan‐1) proliferation in normoxic conditions with LC50 of 4.5 μM. Moreover, its optical properties revealed efficient photosensitizing properties, leading to cancer cells death under light irradiation, making this compound a suitable candidate for photodynamic therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Efficient photosensitizers for photodyanmic therapy (PDT) need to be soluble in physiologic media. This requirement often complicates significantly the chemical access to such compounds, resulting in lower availability and higher production costs for the best representatives. Given that their screening and selection is often initially conducted in organic media from series of hydrophobic model compounds, the possibility to use directly such hydrophobic photosensitizers in real PDT studies was highly desirable to speed up their definitive identification but also to alleviate their cost. In this respect, PMLABe polymeric nanoparticles (NPs) were presently probed as nanocarriers to water-solubilize hydophobic star-shaped porphyrin-based which turned out to be promising oxygen photosensitizers for theranostic approaches. We show here that PDT conducted using such NPs loaded with these compounds is as efficient than when functional hydrosoluble analogues of these photosensitiers are tested alone and that tracking of the photosensitizer by fluorescence imaging is even easier. Star-shaped hydrophobic porphyrins, acting as powerful fluorescent two-photon photosensitizers for oxygen in organic solvents, can easily be loaded into PMLABe polymeric nanoparticles at various concentrations. In this contribution, the performance of these porphyrin-containing nanoparticles in terms of photodynamic therapy (PDT) is compared to those of the corresponding water-soluble porphyrin analogues when irradiated in MCF-7 cancer cells. While quite promising results are obtained for performing PDT with these nanoparticles, validating this approach as a mean for using more easily accessible and less expensive photosensitizers, from a synthetic perspective, we also show that their luminescence can still be used for bioimaging purposes in spite of their confinement in the nanoparticles, validating also the use of these nano-objects for theranostic purposes. [ABSTRACT FROM AUTHOR]

The discovery of novel anticancer chemotherapeutics is fundamental to treat cancer more efficiently. Towards this goal, two dyads consisting of a gold porphyrin appended to organotin(IV) entities were synthesized and their physicochemical and biological properties were characterized. One dyad contains a gold porphyrin connected to a tin(IV) cation via a malonate and two phenyl ligands (AuP-SnPh2), while the other contains two tin(IV) cations each chelated to one carboxylic acid group of the malonate and three phenyl ligands (AuP-Sn2Ph6). The mode of chelation of Sn(IV) to the malonate was elucidated by IR spectroscopy and 119Sn NMR. In the solid state, the complexes exist as coordination polymers in which the tin is penta-coordinated and bridged to two different malonate units. In solution the chemical shifts of 119Sn signals indicate that the tin complexes are in the form of monomeric species associated with a tetra-coordinated tin cation. The therapeutic potential of these new compounds was assessed by determining their cytotoxic activities on human breast cancer cells (MCF-7) and on healthy human fibroblasts (FS 20-68). The study reveals that the dyads are more potent anticancer drugs than the mixture of their individual components (gold porphyrin and reference tin complexes). Therefore, the covalent link of organotin complexes to a gold porphyrin induces a synergistic cytotoxic effect. The dyad AuP-SnPh2 shows high cytotoxicity (0.13 μM) against MCF-7 along with good selectivity for cancer cells versus healthy cells. Finally, it was also shown that the dyad AuP-Sn2Ph6 exhibits a very high anticancer activity (LC50 = 0.024 μM), but the presence of two tin units induces strong cytotoxicity on healthy cells too (LC50 = 0.032 μM). This study underscores, thus, the potential of the association of gold porphyrin and organotin complexes to develop anticancer metallo-drugs. [ABSTRACT FROM AUTHOR]

Abstract Background Most methods available to predict protein epitopes are sequence based. There is a need for methods using 3D information for prediction of discontinuous epitopes and derived immunogenic peptides. Results PEPOP uses the 3D coordinates of a protein both to predict clusters of surface accessible segments that might correspond to epitopes and to design peptides to be used to raise antibodies that target the cognate antigen at specific sites. To verify the ability of PEPOP to identify epitopes, 13 crystallographically defined epitopes were compared with PEPOP clusters: specificity ranged from 0.75 to 1.00, sensitivity from 0.33 to 1.00, and the positive predictive value from 0.19 to 0.89. Comparison of these results with those obtained with two other prediction algorithms showed comparable specificity and slightly better sensitivity and PPV. To prove the capacity of PEPOP to predict immunogenic peptides that induce protein cross-reactive antibodies, several peptides were designed from the 3D structure of model antigens (IA-2, TPO, and IL8) and chemically synthesized. The reactivity of the resulting anti-peptides antibodies with the cognate antigens was measured. In 80% of the cases (four out of five peptides), the flanking protein sequence process (sequence-based) of PEPOP successfully proposed peptides that elicited antibodies cross-reacting with the parent proteins. Polyclonal antibodies raised against peptides designed from amino acids which are spatially close in the protein, but separated in the sequence, could also be obtained, although they were much less reactive. The capacity of PEPOP to design immunogenic peptides that induce antibodies suitable for a sandwich capture assay was also demonstrated. Conclusion PEPOP has the potential to guide experimentalists that want to localize an epitope or design immunogenic peptides for raising antibodies which target proteins at specific sites. More successful predictions of immunogenic peptides were obtained when a peptide was continuous as compared with peptides corresponding to discontinuous epitopes. PEPOP is available for use at http://diagtools.sysdiag.cnrs.fr/PEPOP/.