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This work introduces rationally designed, improved amphiphilic single-chain polymer nanoparticles (SCNPs) for imaging and photodynamic therapy (PDT) in zebrafish embryo xenografts. SCNPs are ultrasmall polymeric nanoparticles with sizes similar to proteins, making them ideal for biomedical applications. Amphiphilic SCNPs result from the self-assembly in water of isolated synthetic polymeric chains through intrachain hydrophobic interactions, mimicking natural biomacromolecules and, specially, proteins (in size and when loaded with drugs, metal ions or fluorophores also in function). These ultrasmall, soft nanoparticles have various applications, including catalysis, sensing, and nanomedicine. Initial in vitro experiments with nonfunctionalized, amphiphilic SCNPs loaded with a photosensitizing Zn phthalocyanine with four nonperipheral isobutylthio substituents, ZnPc, showed promise for PDT. Herein, the preparation of improved, amphiphilic SCNPs containing ZnPc as highly efficient photosensitizer encapsulated within the nanoparticle and surrounded by anthracene units is disclosed. The amount of anthracene groups and ZnPc molecules within each single-chain nanoparticle controls the imaging and PDT properties of these nanocarriers. Critically, this work opens the way to improved PDT applications based on amphiphilic SCNPs as a first step toward ideal, long-term artificial photo-oxidases (APO)., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

This work investigates the electron-donating capabilities of two 10-π electron nitrogen bridgehead bicyclic [5,6]-fused ring systems, imidazo[1,2- a ]pyridine and imidazo[1,5- a ]pyridine rings. Eight compounds with varying positions of electron-withdrawing moieties (TCF or DCI) coupled to the imidazopyridine ring were synthesized and studied. DCI-containing compounds ( Ib - IVb ) exhibited a purely dipolar nature with broad absorption bands, weak fluorescence, large Stokes shifts, and strong solvatochromism. In contrast, TCF-containing compounds ( Ia - IVa ) demonstrated diverse properties. Imidazo[1,2- a ]pyridine derivatives Ia and IIa were purely dipolar, while imidazo[1,5- a ]pyridine derivatives IIIa and IVa displayed a cyanine-like character with intense absorption and higher quantum yields of emission. The observed gradual red shift in optical properties with changing electron-donor groups ( IIb < Ib < IIIb < IVb ) and ( IIa < Ia < IIIa < IVa ) underscores the stronger electron-donor character of imidazo[1,5- a ]pyridine compared to that of imidazo[1,2- a ]pyridine. Furthermore, crystalline powders of imidazo[1,2- a ]pyridine derivatives exhibited fluorescence despite minimal emission in solution. Two compounds ( Ib and IVa ) were successfully formulated into nanoparticles for potential in vivo imaging applications in zebrafish embryos.

Phthalocyanines have been described as effective photosensitizers for photodynamic therapy and are therefore, being studied for their biomedical applications. The metalation of photosensitizers can improve their photodynamic therapy potential. Here, we focus on the biological properties of [1,4-Bis(3,6,9,12-Tetraoxatridec-1-yloxy)phthalocyaninato]zinc(II) (ZnPc(αEG 4 ) 2 ) and demonstrate its exceptional anticancer activity upon light stimulation to kill preferentially cancer cells with a start of efficiency at 10 pM. Indeed, in this work we highlighted the high selectivity of ZnPc(αEG 4 ) 2 for cancer cells compared with healthy ones and we establish its mechanism of action, enabling us to conclude that ZnPc(αEG 4 ) 2 could be a powerful tool for cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Centre Nationale de Recherche Scientifique. Published by Elsevier B.V. All rights reserved.)

Many experiments showed that exogenous ligands could enhance cadmium (Cd) phytoextraction efficiency in soils. Previous studies suggested that the dissociation and the apoplastic uptake of Cd complex could not fully explain the increase of root Cd uptake. Two hypotheses are evaluated to explain enhanced Cd uptake in the presence of ligand: i) enhanced apoplastic uptake of complex due to reduced apoplastic resistance and ii) complex internalization by membrane transporters. RESULTS: show that the ligand affinity for Cd is a key characteristic determining the potential mechanism for enhanced Cd uptake. When low molecular weight organic acids are applied, the complex dissociation could generally be fast (> 10 -3.3 s -1 ) and result in the increased Cd uptake. When hydrophilic aminopolycarboxylic acids (APCAs) are applied in experiments without water or temperature stresses to the plant, the root water uptake flux could very likely be high (> 10 -7.8 dm s -1 ), and the strong apoplastic complex uptake could enhance the root Cd uptake. When lipophilic APCAs are applied, the strong internalization of the complex by membrane transporters could result in the increased Cd uptake if the maximum internalization rate is high (> 10 -12 mol dm -2 s -1 ). However, the complex internalization by membrane transporters must be experimentally confirmed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Contamination of sunflower seeds with soil Cd is an important issue for food and feed because this species strongly accumulates this metal. The present work reports that seeds from three sunflower varieties (ES Biba, Extrasol, Vellox) cultivated in the field in a calcareous agricultural soil having a moderately high Cd content (1 mg Cd/kg) had Cd contents of 0.84, 0.88 and 0.76 mg Cd/kg, respectively, all exceeding the regulation limit of 0.5 mg Cd/kg seeds for human food. On average, for the three varieties, washing seeds did not affect their total Cd contents but slightly increased the Cd in the kernels at the expense of that in hulls. Despite the Cd content of the whole seeds not differing between the varieties, the Cd fraction in the edible kernel differed significantly between varieties from 78 to 87% of the total seed Cd. The results of this study suggest that (i) the size of the kernel, relative to that of the hull, may affect the dilution of Cd in kernel tissues and (ii) there might be genetic variability for the capacity of transfer of Cd from the hull to the kernel. This opens the perspective to increase food safety by selecting sunflower genotypes that retain more Cd into the hull and transfer less of it to the edible kernel., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The concept of using two-photon excitation in the NIR for the spatiotemporal control of biological processes holds great promise. However, its use for the delivery of nucleic acids has been very scarcely described and the reported procedures are not optimal as they often involve potentially toxic materials and irradiation conditions. This work prepares a simple system made of biocompatible porous silicon nanoparticles (pSiNP) for the safe siRNA photocontrolled delivery and gene silencing in cells upon two-photon excitation. PSiNP are linked to an azobenzene moiety, which possesses a lysine group (pSiNP@ICPES-azo@Lys) to efficiently complex siRNA. Non-linear excitation of the two-photon absorber system (pSiNP) followed by intermolecular energy transfer (FRET) to trans azobenzene moiety, result in the photoisomerization of the azobenzene from trans to cis and in the destabilization of the azobenzene-siRNA complex, thus inducing the delivery of the cargo siRNA to the cytoplasm of cells. Efficient silencing in MCF-7 expressing stable firefly luciferase with siRNAluc against luciferase is observed. Furthermore, siRNA against inhibitory apoptotic protein (IAP) leads to over 70% of MCF-7 cancer cell death. The developed technique using two-photon light allows a unique high spatiotemporally controlled and safe siRNA delivery in cells in few seconds of irradiation., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Herein, we report for the first time a biocompatible cross-linked trianglamine (Δ) network for the efficient iodine removal from the vapor phase, water, and seawater. In the vapor phase, the cross-linked network could capture 6 g g -1 of iodine, ranking among the most performant materials for iodine vapor capture. In the liquid phase, this cross-linked network is also capable of capturing iodine at high rates from aqueous media (water and seawater). This network displayed fast adsorption kinetics, and they are fully recyclable. This study reveals the high affinity of iodine for the intrinsic cavity of the trianglamine. The synthesized materials are extremely interesting since they are environmentally friendly and inexpensive and the synthesis could easily be scaled up to be used as the material of choice in response to accidents in the nuclear industry.

Drug-targeted delivery has become a top priority in the world of medicine in order to develop more efficient therapeutic agents. This is important as a critical underlying problem in cancer therapy stems from the inability to deliver active therapeutic substances directly to tumor cells without causing collateral damage. In this work, zinc(II) phthalocyanine (ZnPc) was selected as a sensitizer and was linked to different targeting agents, which would be recognized by overexpressed proteins in cancer cells. As targeting agents, we first selected the two ligands ( DAA1106 ,  PK11195 ) of the translocator protein ( TSPO ) and then  Erlotinib  a binding group of the ATP domain of tyrosine kinase in epidermal growth factor (EGFR). ZnPc was connected via an ethylene glycol chain to either one ( n = 1) or four ( n = 4) targeting agents. The biological activity of these conjugates ZnPc(ligand) n was investigated on MDA-MB-231 breast human cancer cells and human hepatoma HepG2 cells, first in the dark (cytotoxicity) and then under irradiation (photodynamic therapy). The dark cytotoxicity was extremely low (IC 50 ≥ 50 μM) for all of these compounds, which is a required criterion for further photodynamic application. After irradiation at 650 nm, only the conjugates bearing one targeting ligand such as ZnPc-[DAA1106]1, ZnPc-[PK11195]1, and ZnPc-[Erlo]1 showed photodynamic activity, while those linked to 4 targeting agents were inactive. Importantly, fluorescence imaging microscopy showed the colocalization of ZnPc-[DAA1106]1, ZnPc-[PK11195]1 and ZnPc-[erlo]1, at mitochondria, a result that justifies the observed photodynamic activity of these conjugates. This study first shows the impact of the number and the mode of organization of targeting agents on the ability of the sensitizer to cross the cell membrane. When zinc(II) phthalocyanine carries a single targeting agent, a significant photodynamic activity on MDA-MB-231 breast human cancer cells was measured and localization at the mitochondria was demonstrated by fluorescence imaging, thus proving the potential of the sensitizer linked to a targeting agent to improve selectivity. Another important conclusion from this study for the design of future effective PDT drugs using multivalence effects is to control the arrangement of the targeting agents in order to design molecules that will be able to pass the cell membrane barriers.

Anopheles darlingi is the main vector of malaria in South America. In French Guiana, malaria transmission occurs inland and along the rivers with a regular reemergence in the lower Oyapock area. Control against malaria vectors includes indoor residual spraying of deltamethrin and the distribution of long-lasting impregnated bednets. In this context, the level of resistance to pyrethroids was monitored for 4 years using CDC bottle tests in An. darlingi populations. A loss of susceptibility to pyrethroids was recorded with 30-minute knock-down measured as low as 81%. However, no pyrethroid molecular resistance was found by sequencing a 170 base pair fragment of the S6 segment of domain II of the voltage-gated sodium channel gene. Fluctuation of resistance phenotypes may be influenced by the reintroduction of susceptible alleles from sylvatic populations or by other mechanisms of metabolic resistance.

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 NH 2 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.

The objective of this study was to assess the effects of different intensities of biomass harvesting, and the possible effects of compensation methods, on forest functioning. To do so, we carried out a split-plot experiment (SW France) crossing four different intensities of biomass harvesting (Stem-Only Harvest [SOH], Aboveground Additional Harvest [AAH], Belowground Additional Harvest [BAH], and Whole-Tree Harvest [WTH]) and three compensation methods (control [C], wood ash application [A] and phosphorus fertilisation [P]). The experimental treatments were followed by the plantation of pines (Pinus pinaster). The environmental consequences of treatments on soil and vegetation were evaluated 11 years after the tree plantation. Despite their low additional biomass exports (+10 % for AAH to +34 % for WTH), the non-conventional harvest practices exported much higher quantities of nutrients than the conventional SOH technique (+145 % of exported N in WTH). Additional biomass harvests impacted the soil organic matter content, with negative effects on P -organic , soil cation exchange capacity, exchangeable Ca, and most extractible nutrients. However, tree nutritional status was improved by P-fertiliser or wood ash. We observed a positive effect of wood ash application on soil pH and nutrient content but, like additional harvests, wood ash application decreased the pool of soil organic carbon (~10 %). Overall, the experiment showed that exporting more forest biomass due to the additional harvesting of biomass had negative consequences on the ecosystem biogeochemistry. Additional harvests have impoverished the soil, and decreased the soil organic carbon content. Importantly, applying nutrients as fertiliser or wood ash did not compensate for all the negative impacts of biomass exports and the method of wood ash recycling in forests could even decrease the soil organic carbon., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., Competing Interests: ÉS, J-PB, and CN were employed by Empreinte Humaine. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sandrin, Brun, Nguyen, Biron and Ivers.)

Durum wheat is one of the cereal crops that accumulates the highest concentrations of cadmium (Cd) and deoxynivalenol (DON) mycotoxin in its grains, thereby affecting the safety of products made of durum wheat grains (pasta and semolina). This study investigates in planta the interaction between Cd and Fusarium graminearum , the main causal agent of DON accumulation in grains. A pot experiment was designed to characterize the response of durum wheat to F. graminearum infection at three levels of Cd exposure: 0.1, 2, and 10 mg Cd kg -1 soil, which showed that the accumulation of Cd and DON resulted from interacting processes. On the one hand, plant exposure to Cd reduced the concentration of DON in grains. The mitigating effect of Cd on DON accumulation was attributed to the restricted growth of F. graminearum , which could result from enhanced plant resistance to the fungal pathogen induced by Cd exposure. On the other hand, F. graminearum infection of durum wheat increased the Cd concentration in the grains. The promoting effect of Fusarium infection on Cd accumulation was attributed to decoupling of the allocation of Cd and photoassimilates to the grains and to the reduced strength of the grain sink for photoassimilates caused by the fungus. Provided that this result is confirmed in field conditions, it suggests that in Cd-contaminated soils, particular attention should be paid to agronomic practices that affect Fusarium head blight disease to avoid further increase in the risk of exceeding the regulatory limit set by the European Union for Cd in durum wheat.

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.

Accumulation of copper (Cu) in soils due to the application of fungicides may be toxic for organisms and hence affect winegrowing sustainability. Soil parameters such as pH and dissolved organic matter (DOM) are known to affect the availability of Cu. In this study, we investigated the contribution of chromophoric and fluorescent DOM properties to the prediction of Cu availability in 18 organic vineyard soils in the Bordeaux winegrowing area (France). The DOM parameters, assessed through absorbance and fluorescence analyses, and proxies for Cu availability (total soluble Cu and free ionic Cu 2+ ) were measured in 0.01 M KCl extracts. Total soluble Cu (Cu KCl ) varied 23-fold while free ionic Cu 2+ varied by a factor of 4600 among the soils. DOC concentrations were similar among the soils, but the samples differed in the quality of DOM as assessed by optical spectroscopy. Multilinear regression models with and without DOM quality parameters were investigated to predict Cu availability. The best model for Cu KCl successfully explained 83% of variance and included pH, Cu T , and two DOM fluorescence quality indices, the FI fluorescence index, which distinguishes between microbial and higher plant origins, and the HIX humification index. For the prediction of Cu 2+ , pH alone explained 88% of variance and adding DOM parameters did not improve modelling. The two Cu availability proxies were related to pH. This study confirms the prominent role of pH in Cu availability and underlines the importance of DOM quality to better predict Cu solubility., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Speciation of Cd in soil solutions strongly determines the fate of this toxic metal in the environment. Generally, in soil solutions, Cd predominantly binds to the dissolved organic matter (DOM). The determination of the quantity and reactivity of DOM that actually complexes Cd in soil solutions is challenging for operational purposes. Therefore, this study tested whether Cd 2+ concentration in soil solutions could effectively be predicted by considering complexation with a single mean organic ligand assumed to be a fraction of DOM of unspecified nature or assumed to be purely fulvic acids (FA) with reactivity as described in WHAM VII. The reactivity of the unspecified ligand and the concentration of FA were modelled and fitted to experimental data from 76 agricultural soils with low Cd contents. The optimal reactivity and FA concentration that minimized the relative error (RE) of predictions of the concentration of Cd 2+ in soil solutions were either considered constant across soils or modelled from soil properties by multiple linear regressions (MLR) or random forests (RF), giving 6 models, the predictive value of which was assessed by 10-folds cross-validation. When the reactivity of the mean ligand and the optimal FA concentration were considered constant across soils, the models were biased and 66.9% of predictions had relative errors below a factor of 2. By contrast, if the reactivity of the mean ligand or the optimal FA concentration were allowed to vary with soil characteristics, these performances increased to 95.5%, soil pH being the main predictor and RF being slightly more efficient than MLR. With more than 95% of the relative errors of prediction below a factor of 2, the models developed in this work could be valuable for assessing Cd speciation in the solution of soils having a low Cd content., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

The efficient, versatile, and straightforward synthesis of the first N -alkyl analogues of induline 3B ( 8a and 8b ) is reported. Thanks to the introduction of lipophilic substituents and their attractive photophysical properties (far-red emission and production of singlet oxygen), phenazinium 8b can be used as a theranostic agent and shows, at very low concentrations (100 nM), a remarkable ability to (i) image cells and zebrafish embryos with high quality under both mono- (514 nm) and biphotonic (790 and 810 nm) excitations, (ii) efficiently and quickly penetrate cancer cells rather than healthy fibroblasts, and (iii) induce a total or almost total cancer cell death in vitro and in vivo after illumination (λ exc = 540-560 nm). The molecular structure of 8b is based on a triamino-phenazinium core only, with no need for additional components, highlighting the emergence of a minimalistic and versatile class of fluorescent probes for targeted photodynamic cancer therapy.

Antibodies not only play a major role in clinical diagnostics and biopharmaceutical analysis but also are a class of drugs that are regularly used to treat numerous diseases. The identification of antibody-epitope binding sites is then of great interest to many emerging medical and bioanalytical applications, particularly to design monoclonal antibodies (mAb) mimics taking advantage of amino acid residues involved in the binding. Among relevant antibodies, the monoclonal antibody rituximab has received significant attention as it is exploited to treat several cancers including non-Hodgkin's lymphoma and chronic lymphocytic leukemia, as well as some autoimmune disorders such as rheumatoid arthritis. The binding of rituximab to the targeted cells occurs via the recognition of the CD20 epitope. A crystallographic study has shown that the binding area, named paratope, is located at the surface of rituximab. Combining the SPOT method and the complementary surface plasmon resonance technique allowed us to detect an extended recognition domain buried in the pocket of the rituximab Fab formed by four β-sheets. More generally, the present study offers a comprehensive approach to identify antibody-epitope binding sites.

The combination of photodynamic therapy and chemotherapy is a promising strategy to enhance cancer therapeutic efficacy and reduce drug resistance. In this study two zinc(II) phthalocyanine-tin(IV) conjugates linked by a triethylene glycol chain were synthesized and characterized. In these complexes, the zinc(II) phthalocyanine was used as a potential photosensitizer for PDT and the tin complex was selected as cytostatic moiety. The two dyads composed of zinc(II) phthalocyanine and tin complexes exhibited high cytotoxicity, in absence of light stimulation, against MCF-7 human breast cancer cells with low LC 50 values in the range of 0.016-0.453 µM. In addition, these complexes showed superior cytotoxicity than their mixture of equimolar component, accompanied with a higher activity towards cancer cells compared to human healthy fibroblasts. However, under irradiation of the zinc phthalocyanine unit (at 650 nm) no photodynamic activity could be detected, due to the most likely quenching of zinc(II) phthalocyanine singlet excited state by the nearby tin complex according to a photoinduced electron transfer process. This study demonstrates the potential of heterometallic anticancer chemotherapeutics composed of a zinc phthalocyanine and tin complex, and it highlights that the development of such conjugates requires that the sensitizer preserves its photophysical properties and in particular its singlet oxygen sensitization ability in the conjugate in order to combine the PDT activity with the cytotoxicity of the anticancer drug.

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-SnPh 2 ), while the other contains two tin(iv) cations each chelated to one carboxylic acid group of the malonate and three phenyl ligands (AuP-Sn 2 Ph 6 ). The mode of chelation of Sn(iv) to the malonate was elucidated by IR spectroscopy and 119 Sn 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 119 Sn 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-SnPh 2 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-Sn 2 Ph 6 exhibits a very high anticancer activity (LC 50 = 0.024 μM), but the presence of two tin units induces strong cytotoxicity on healthy cells too (LC 50 = 0.032 μM). This study underscores, thus, the potential of the association of gold porphyrin and organotin complexes to develop anticancer metallo-drugs.

Contamination of durum wheat grain by cadmium (Cd) threatens food safety and is of increasing concern because regulations concerning Cd are becoming stricter due to its toxicity. This work aimed at using soil variables and cultivar types to build models to predict whether durum wheat grain Cd will conform with current and possibly lower regulatory thresholds. We combined multiple Gaussian and logistic regressions and the random forest algorithm to take advantage of their strength. Models tested using cross-validation produced excellent performances including for the lowest regulatory threshold of 0.1 mg Cd/kg, half of the current one: 79-85% of the non-conformity cases were detected and the reliability of predictions was 69-82%. The models enabled identification of a x1.4 variability in grain Cd content between cultivars that do not have the low Cd accumulation allele of the Cdu1 gene. The models confirmed that for the grain Cd content, the between-cultivar variability had much less influence than the phytoavailability of Cd in soil, the critical contexts of which were characterized by the models. For farmers, these models are valuable tools to predict whether durum wheat production will conform with existing and future Cd regulation in foodstuffs., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In French Guiana, the malaria, a parasitic infection transmitted by Anopheline mosquitoes, remains a disease of public health importance. To prevent malaria transmission, the main effective way remains Anopheles control. For an effective control, accurate Anopheles species identification is indispensable to distinguish malaria vectors from non-vectors. Although, morphological and molecular methods are largely used, an innovative tool, based on protein pattern comparisons, the Matrix Assisted Laser Desorption / Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) profiling, emerged this last decade for arthropod identification. However, the limited mosquito fauna diversity of reference MS spectra remains one of the main drawback for its large usage. The aim of the present study was then to create and to share reference MS spectra for the identification of French Guiana Anopheline species. A total of eight distinct Anopheles species, among which four are malaria vectors, were collected in 6 areas. To improve Anopheles identification, two body parts, legs and thoraxes, were independently submitted to MS for the creation of respective reference MS spectra database (DB). This study underlined that double checking by MS enhanced the Anopheles identification confidence and rate of reliable classification. The sharing of this reference MS spectra DB should make easier Anopheles species monitoring in endemic malaria area to help malaria vector control or elimination programs., Competing Interests: The authors declare that they have no competing interests.

In this work, we exploit the versatile function of cationic phosphonium-conjugated polythiophenes to develop multifunctional platforms for imaging and combined therapy (siRNA delivery and photodynamic therapy). The photophysical properties (absorption, emission and light-induced generation of singlet oxygen) of these cationic polythiophenes were found to be sensitive to molecular weight. Upon light irradiation, low molecular weight cationic polythiophenes were able to light-sensitize surrounding oxygen into reactive oxygen species (ROS) while the highest were not due to its aggregation in aqueous media. These polymers are also fluorescent, allowing one to visualize their intracellular location through confocal microscopy. The most promising polymers were then used as vectors for siRNA delivery. Due to their cationic and amphipathic features, these polymers were found to effectively self-assemble with siRNA targeting the luciferase gene and deliver it in MDA-MB-231 cancer cells expressing luciferase, leading to 30-50% of the gene-silencing effect. In parallel, the photodynamic therapy (PDT) activity of these cationic polymers was restored after siRNA delivery, demonstrating their potential for combined PDT and gene therapy.

Porphyrin-based periodic mesoporous organosilica nanoparticles (PMO) synthesized from a large functional octatriethoxysilylated porphyrin precursor and allowing two-photon excitation photodynamic therapy (TPE-PDT) and NIR imaging were synthesized. These PMO were grafted with polyethylene glycol (PEG) moieties and an analogue of mannose 6-phosphate functionalized at the anomeric position (AMFA). AMFAs are known to efficiently target mannose 6-phosphate receptors (M6PRs) which are over-expressed in various cancers. Here, we demonstrated for the first time that M6PRs were over-expressed in rhabdomyosarcoma (RMS) cells and could be efficiently targeted with PMO-AMFA allowing TPE imaging and TPE-PDT of RMS cells. The comparison with healthy myoblasts demonstrated an absence of biological effects, suggesting a cancer cell specificity in the biomedical action observed.

In addition to the already described ligand L 4a , two pyclen-based lanthanide chelators, L 4b and L 4c , bearing two specific picolinate two-photon antennas (tailor-made for each targeted metal) and one acetate arm arranged in a dissymmetrical manner, have been synthesized, to form a complete family of lanthanide luminescent bioprobes: [Eu L 4a ], [Sm L 4a ], [Yb L 4b ], [Tb L 4c ], and [Dy L 4c ]. Additionally, the symmetrically arranged regioisomer L 4a' was also synthesized as well as its [Eu L 4a' ] complex to highlight the astonishing positive impact of the dissymmetrical N -distribution of the functional chelating arms. The investigation clearly shows the high performance of each bioprobe, which, depending on the complexed lanthanide, could be used in various applications. Each presents high brightness, quantum yields, and lifetimes. Staining of the complexes into living human breast cancer cells was observed. In addition, in vivo two-photon microscopy was performed for the first time on a living zebrafish model with [Eu L 4a ]. No apparent toxicity was detected on the growth of the zebrafish, and images of high quality were obtained.

Understanding how essential and toxic elements are distributed in cereal grains is a key to improving the nutritional quality of cereal-based products. The main objective of this work was to characterize the distribution of Cd and of nutrients (notably Cu, Fe, Mn, P, S and Zn) in the durum wheat grain. Laser ablation inductively coupled mass spectrometry and synchrotron micro X-ray fluorescence were used for micro-scale mapping of Cd and nutrients. A dissection approach was used to quantitatively assess the distribution of Cd and nutrients among grain tissues. Micro X-ray absorption near-edge spectroscopy was used to identify the Cd chemical environment in the crease. Cadmium distribution was characterized by strong accumulation in the crease and by non-negligible dissemination in the endosperm. Inside the crease, Cd accumulated most in the pigment strand where it was mainly associated with sulfur ligands. High-resolution maps highlighted very specific accumulation areas of some nutrients in the germ, for instance Mo in the root cortex primordia and Cu in the scutellum. Cadmium loading into the grain appears to be highly restricted. In the grain, Cd co-localized with several nutrients, notably Mn and Zn, which challenges the idea of selectively removing Cd-enriched fractions by dedicated milling process., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Herein hybrid silica nanoparticles have been engineered to direct the sequential delivery of multiple chemotherapeutic drugs in response to external stimuli such as variations in pH. The nanocarriers consist of conventional MCM-41-type nanoparticles, which have been functionalised with an organic ligand (or stalk) grafted onto the external surface. The stalk is designed to "recognise" a complementary molecule, which serves as a "cap" to block the pores of the nanoparticles. First, camptothecin is introduced into the pores by diffusion prior to capping the pore apertures via molecular recognition. The cap, which is a derivative of 5-fluorouracil, serves as a second cytotoxic drug for synergistic chemotherapy. In vitro tests revealed that negligible release of the drugs occurred at pH 7.4, thus avoiding toxic side effects in the blood stream. In contrast, the stalk/cap complex is destabilised within the endolysosomal compartment (pH 5.5) of cancer cells, where release of the drugs was demonstrated. Furthermore, this environmentally responsive system exhibited a synergistic effect of the two drugs, where the pH-triggered release of the cytotoxic cap followed by diffusion-controlled release of the drug cargo within the pores led to essentially complete elimination of breast cancer cells.

The desorption rate is an important factor determining cadmium (Cd) ecotoxicity and pollution remediation in soils. The pedotransfer functions (PTFs) of desorption rate coefficients of fresh Cd in soils have been developed in literature. We hypothesized that the aging of Cd pollution would alter Cd desorption process. Taking historically polluted soils as the object, this study aimed at testing the hypothesis and developing new PTFs of desorption rate coefficients for historical Cd. 15 d batch extraction experiments and 13 kinetic models were employed to define Cd desorption rate coefficients in 27 historically polluted soil samples. Compared with fresh Cd, the desorption rate coefficients of historical Cd were lower, and the break time of biphasic desorption processes was retarded to 3 d (4320 min). Different with the usual models for fresh Cd desorption (e.g. parabolic diffusion and two constant rate models), the best models to mimic the historical Cd desorption processes were the pseudo first order, logarithmic, Elovich, and simple Elovich models. The rate-limiting step controlling Cd desorption was changed from the intraparticle diffusion to the interface reaction with aging of pollution. New PTFs of desorption rate coefficients of historical Cd were established (R 2  ≥ 0.71). Cd desorption rate coefficients increased with organic matter and clay contents, but decreased with oxalate extractable Fe content, solution pH, cation exchange capacity, and silt content. The key soil properties influencing desorption rate coefficients were not altered by the aging of pollution. The developed PTFs could guide us to adjusting the ecotoxicity and pollution remediation of Cd in historically polluted field soils., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

(1) Background: Nanomedicine has recently emerged as a promising field, particularly for cancer theranostics. In this context, nanoparticles designed for imaging and therapeutic applications are of interest. We, therefore, studied the encapsulation of upconverting nanoparticles in mesoporous organosilica nanoparticles. Indeed, mesoporous organosilica nanoparticles have been shown to be very efficient for drug delivery, and upconverting nanoparticles are interesting for near-infrared and X-ray computed tomography imaging, depending on the matrix used. (2) Methods: Two different upconverting-based nanoparticles were synthesized with Yb 3+ -Er 3+ as the upconverting system and NaYF 4 or BaLuF 5 as the matrix. The encapsulation of these nanoparticles was studied through the sol-gel procedure with bis(triethoxysilyl)ethylene and bis(triethoxysilyl)ethane in the presence of CTAB. (3) Results: with bis(triethoxysilyl)ethylene, BaLuF 5 : Yb 3+ -Er 3+ , nanoparticles were not encapsulated, but anchored on the surface of the obtained mesoporous nanorods BaLuF 5 : Yb 3+ -Er 3+ @Ethylene. With bis(triethoxysilyl)ethane, BaLuF 5 : Yb 3+ -Er 3+ and NaYF 4 : Yb 3+ -Er 3+ nanoparticles were encapsulated in the mesoporous cubic structure leading to BaLuF 5 : Yb 3+ -Er 3+ @Ethane and NaYF 4 : Yb 3+ -Er 3+ @Ethane, respectively. (4) Conclusions: upconversion nanoparticles were located on the surface of mesoporous nanorods obtained by hydrolysis polycondensation of bis(triethoxysilyl)ethylene, whereas encapsulation occurred with bis(triethoxysilyl)ethane. The later nanoparticles NaYF 4 : Yb 3+ -Er 3+ @Ethane or BaLuF 5 : Yb 3+ -Er 3+ @Ethane were promising for applications with cancer cell imaging or X-ray-computed tomography respectively.

The 300 kDa cation-independent M6P receptor (CI-MPR) mediates ligand internalization and trafficking to the endolysosomal compartments. Because of its endocytotic nature, it has been recognized as a promising class of receptors for target component delivery. Its cellular uptake involves the simultaneous binding of two protein units resulting in the formation of receptor dimers. While many multivalent glycoconjugates have been reported to date, little is known about the topological requests to induce an effective recruitment of CI-MPRs. We herein describe the synthesis and cell uptake ability of a set of highly organized glycoclusters bearing one to three saccharide units. The spatial arrangement of carbohydrate ligands is ensured by a heterocyclic γ-peptide central core.

The photophysical properties of a new series of fluorenyl porphyrins bearing water-solubilising oligoethyleneglycol chains are described. These biocompatible compounds present very good two-photon absorption and singlet oxygen generation properties, while retaining some fluorescence in water. After testing in vitro on breast cancer cells, some of them were shown to be efficient non-toxic two-photon photosensitisers allowing for fluorescence imaging, thus demonstrating their theranostic potential.

Background: Bridged silsesquioxane nanoparticles (BSNs) recently described represent a new class of nanoparticles exhibiting versatile applications and particularly a strong potential for nanomedicine., Aims: In this work, we describe the synthesis of BSNs from an octasilylated functional porphyrin precursor (PORBSNs) efficiently obtained through a click reaction. These innovative and very small-sized nanoparticles were functionalized with PEG and mannose (PORBSNs-mannose) in order to target breast tumors in vivo., Methods and Results: The structure of these nanoparticles is constituted of porphyrins J aggregates that allow two-photon spatiotemporal excitation of the nanoparticles. The therapeutic potential of such photoactivable nanoparticles was first studied in vitro, in human breast cancer cells in culture and then in vivo on zebrafish embryos bearing human tumors. These animal models were intravenously injected with 5 nL of a solution containing PORBSNs-mannose. An hour and half after the injection of photoactivable and targeted nanoparticles, the tumor areas were excited for few seconds with a two-photon beam induced focused laser. We observed strong tumor size decrease, with the involvement of apoptosis pathway activation., Conclusion: We demonstrated the high targeting, imaging, and therapeutic potential of PORBSNs-mannose injected in the blood stream of zebrafish xenografted with human tumors., (© 2019 Wiley Periodicals, Inc.)

Mesoporous organosilica nanoparticles (PHT-PMO) have been prepared from an octa-triethoxysilylated Zn phthalocyanine precursor. These PHT-PMO nanoparticles had no dark toxicity but high phototoxicity when irradiated at 650 nm, and remarkable near-infrared phototoxicity when excited at 760 and 810 nm. The PHT-PMO were then aminated to promote electrostatic complexation with siRNA. Transfection experiments were performed upon NIR irradiation and photochemical internalization was very efficient, leading to 65% luciferase extinction in MCF-7 cancer cells expressing stable luciferase.

Recently, gold(III) porphyrins have gained great interest as anticancer drugs not only for the stability of gold(III) but also for the functionalization of the porphyrin to allow bridging with another metal such as platinum(II). We report here, for the first time, the synthesis of three new bimetal compounds containing a gold(III) porphyrin conjugated to a platinum diamine moiety through malonate bridging to obtain enhanced cytotoxicity from both metals combined with the phototoxicity of the porphyrin. The three complexes differ in the type of diamine ligand around platinum(II): ammonia (NH 3 ), cyclohexanediamine (CyDA), and pyridylmethylamine (Py). The synthesis was carried out using the complexation of activated malonic acid derivatives with aquadiaminoplatinum(II) complexes, and the products were characterized by IR, NMR, mass spectra, and elementary analysis. The cytotoxic activity of the conjugates was screened in both healthy cell lines and cancer cell lines, human fibroblast cells (FS-68) and human breast cancer cells (MCF-7), and was compared to that of the corresponding platinum(II) complexes. The cyclohexyldiamine (CyDA) derivative exhibited the greatest cytotoxic effect among the series. The results showed that Au(III)/Pt(II) conjugates are more potent by 2-5.6-fold than the corresponding platinum complexes. Moreover, the dyad AuP-PtCyDA is 18% more potent and also more selective toward cancer cells than the parent gold porphyrin substituted with malonic acid. On the other hand, the IC 50 of the dyad AuP-PtCyDA is 43% lower than that of AuTPP but is more selective toward healthy cells. Singlet oxygen measurements indicated that gold(III) porphyrin derivatives are poor oxygen sensitizers and cell death occurred potentially due to generation of other reactive oxygen species (ROS) upon reductive quenching of the gold porphyrin excited state. In addition, the increase in cancer cell death obtained after light irradiation is totally absent in healthy cells, demonstrating the specificity of this PDT treatment on cancer cells. Our findings imply that the incorporation of two different cytotoxic metals in the same molecule represents a remarkable cytotoxic effect in comparison to traditional homometallic Pt(II) drugs.

Background: Bioinformatics methods are helpful to identify new molecules for diagnostic or therapeutic applications. For example, the use of peptides capable of mimicking binding sites has several benefits in replacing a protein which is difficult to produce, or toxic. Using peptides is less expensive. Peptides are easier to manipulate, and can be used as drugs. Continuous epitopes predicted by bioinformatics tools are commonly used and these sequential epitopes are used as is in further experiments. Numerous discontinuous epitope predictors have been developed but only two bioinformatics tools have been proposed so far to predict peptide sequences: Superficial and PEPOP 2.0. PEPOP 2.0 can generate series of peptide sequences that can replace continuous or discontinuous epitopes in their interaction with their cognate antibody., Results: We have developed an improved version of PEPOP (PEPOP 2.0) dedicated to answer to experimentalists' need for a tool able to handle proteins and to turn them into peptides. The PEPOP 2.0 web site has been reorganized by peptide prediction category and is therefore better formulated to experimental designs. Since the first version of PEPOP, 32 new methods of peptide design were developed. In total, PEPOP 2.0 proposes 35 methods in which 34 deal specifically with discontinuous epitopes, the most represented epitope type in nature., Conclusion: Through the presentation of its user-friendly, well-structured new web site conceived in close proximity to experimentalists, we report original methods that show how PEPOP 2.0 can assist biologists in dealing with discontinuous epitopes.

Two trispicolinate 1,4,7-triazacyclonane (TACN)-based ligands bearing three picolinate biphotonic antennae were synthetized and their Yb 3+ and Gd 3+ complexes isolated. One series differs from the other by the absence (L 1 )/presence (L 2 ) of bromine atoms on the antenna backbone, offering respectively improved optical and singlet-oxygen generation properties. Photophysical properties of the ligands, complexes and micellar Pluronic suspensions were investigated. Complexes exhibit high two-photon absorption cross-section combined either with NIR emission (Yb) or excellent 1 O 2 generation (Gd). The very large intersystem crossing efficiency induced by the combination of bromine atom and heavy rare-earth element was corroborated with theoretical calculations. The 1 O 2 generation properties of L 2 Gd micellar suspension under two-photon activation leads to tumour cell death, suggesting the potential of such structures for theranostic applications., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The aim of the present work is the development of highly efficient targeting molecules to specifically address mesoporous silica nanoparticles (MSNs) designed for the photodynamic therapy (PDT) of prostate cancer. We chose the strategy to develop a novel compound that allows the improvement of the targeting of the cation-independent mannose 6-phosphate receptor, which is overexpressed in prostate cancer. This original sugar, a dimannoside-carboxylate (M6C-Man) grafted on the surface of MSN for PDT applications, leads to a higher endocytosis and thus increases the efficacy of MSNs.

Diazachlorin and diazabacteriochlorin have been prepared through reduction of diazaporphyrin and their in vitro and in vivo activity in photodynamic therapy has been investigated.

Epitope identification is essential for developing effective antibodies that can detect and neutralize bioactive proteins. Computational prediction is a valuable and time-saving alternative for experimental identification. Current computational methods for epitope prediction are underused and undervalued due to their high false positive rate. In this work, we targeted common properties of linear B-cell epitopes identified in an individual protein class (metalloendopeptidases) and introduced an alternative method to reduce the false positive rate and increase accuracy, proposing to restrict predictive models to a single specific protein class. For this purpose, curated epitope sequences from metalloendopeptidases were transformed into frame-shifted Kmers (3 to 15 amino acid residues long). These Kmers were decomposed into a matrix of biochemical attributes and used to train a decision tree classifier. The resulting prediction model showed a lower false positive rate and greater area under the curve when compared to state-of-the-art methods. Our predictions were used for synthesizing peptides mimicking the predicted epitopes for immunization of mice. A predicted linear epitope that was previously undetected by an experimental immunoassay was able to induce neutralizing-antibody production in mice. Therefore, we present an improved prediction alternative and show that computationally identified epitopes can go undetected during experimental mapping.

The dissociation of metal complexes in the soil solution can increase the availability of metals for root uptake. When it is accounted for in models of bioavailability of soil metals, the number of partial differential equations (PDEs) increases and the computation time to numerically solve these equations may be problematic when a large number of simulations are required, for example for sensitivity analyses or when considering root architecture. This work presents analytical solutions for the set of PDEs describing the bioavailability of soil metals including the kinetics of complexation for three scenarios where the metal complex in solution was fully inert, fully labile, or partially labile. The analytical solutions are only valid i) at steady-state when the PDEs become ordinary differential equations, the transient phase being not covered, ii) when diffusion is the major mechanism of transport and therefore, when convection is negligible, iii) when there is no between-root competition. The formulation of the analytical solutions is for cylindrical geometry but the solutions rely on the spread of the depletion profile around the root, which was modelled assuming a planar geometry. The analytical solutions were evaluated by comparison with the corresponding PDEs for cadmium in the case of the French agricultural soils. Provided that convection was much lower than diffusion (Péclet's number<0.02), the cumulative uptakes calculated from the analytic solutions were in very good agreement with those calculated from the PDEs, even in the case of a partially labile complex. The analytic solutions can be used instead of the PDEs to predict root uptake of metals. The analytic solutions were also used to build an indicator of the contribution of a complex to the uptake of the metal by roots, which can be helpful to predict the effect of soluble organic matter on the bioavailability of soil metals., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Regulatory limits on cadmium (Cd) content in food products are tending to become stricter, especially in cereals, which are a major contributor to dietary intake of Cd by humans. This is of particular importance for durum wheat, which accumulates more Cd than bread wheat. The contamination of durum wheat grain by Cd depends not only on the genotype but also to a large extent on soil Cd availability. Assessing the phytoavailability of Cd for durum wheat is thus crucial, and appropriate methods are required. For this purpose, we propose a statistical model to predict Cd accumulation in durum wheat grain based on soil geochemical properties related to Cd availability in French agricultural soils with low Cd contents and neutral to alkaline pH (soils commonly used to grow durum wheat). The best model is based on the concentration of total Cd in the soil solution, the pH of a soil CaCl 2 extract, the cation exchange capacity (CEC), and the content of manganese oxides (Tamm's extraction) in the soil. The model variables suggest a major influence of cadmium buffering power of the soil and of Cd speciation in solution. The model successfully explains 88% of Cd variability in grains with, generally, below 0.02 mg Cd kg -1 prediction error in wheat grain. Monte Carlo cross-validation indicated that model accuracy will suffice for the European Community project to reduce the regulatory limit from 0.2 to 0.15 mg Cd kg -1 grain, but not for the intermediate step at 0.175 mg Cd kg -1 . The model will help farmers assess the risk that the Cd content of their durum wheat grain will exceed regulatory limits, and help food safety authorities test different regulatory thresholds to find a trade-off between food safety and the negative impact a too strict regulation could have on farmers.

A partial pancreaticogastrodudenectomy was performed on a 66-year old man with type 2 diabetes mellitus because of an invasive, moderately differentiated adenocarcinoma in the head of the pancreas. In the adjacent grossly normal tissue of the uncinate process, there was a massive proliferation of pancreatic polypeptide (PP) cells confined to this region and showed invasive pattern. Strikingly, in the heaped area of his duodenum, there was a strikingly large number of PP, glucagon, a few insulin cells in a mini-islet-like patterns composed of glucagon and insulin cells. Among the etiological factors, the possible long-lasting effects of the GLP-1 analog, with which the patient was treated, are discussed. This is the first report in the literature of both the coexistence of a pancreatic adenocarcinoma and invasive PPoma and the occurrence of PP and insulin cells in human duodenal mucosa.

To assess the prevalence of malaria among illegal gold miners in the French Guiana rainforest, we screened 205 miners during May-June 2014. Malaria prevalence was 48.3%; 48.5% of cases were asymptomatic. Patients reported self-medication with artemisinin-based combination therapy. Risk for emergence and spread of artemisinin resistance among gold miners in the rainforest is high.

A 5-month experiment was performed to study the accumulation of several inorganic elements in tomato plants cultivated using organic or synthetic fertilizer. Plants were harvested in triplicate at six sampling dates during their life cycle. Statistical and chemometric analysis of data indicated the sequestration of toxic elements and of Na, Zn, Fe, and Co in roots, while the rest of the elements, including Cd, were mainly translocated to aboveground organs. A general decreasing trend in element concentrations with time was observed for most of them. A negative correlation between some element concentrations and ripening stage of fruits was identified. Conventionally grown plants seemed to accumulate more Cd and Tl in their tissues, while organic ones were richer in some nutrients. However, there was no clear effect of the fertilizer used (organic vs synthetic) on the elemental composition of fruits.

Sentinel lymph node biopsy (SLNB) is used to detect axillary lymph node metastases in breast cancer. Preoperative radiocolloid injection with lymphoscintigraphy (PL) is performed before SLNB. Few comparisons between 1- and 2-day PL protocols exist. Opponents of a 2-day protocol have expressed concerns of radiotracer washout to nonsentinel nodes. Proponents cite lack of scheduling conflicts between PL and surgery. A total of 387 consecutive patients with clinically node-negative breast cancer underwent SLNB with PL. Lymphoscintigraphy images were obtained within 30 minutes of radiocolloid injection. Axillary lymph node dissection was performed if the sentinel lymph node (SLN) could not be identified. Data were collected regarding PL technique and results. In all, 212 patients were included in the 2-day PL group and 175 patients in the 1-day PL group. Lymphoscintigraphy identified an axillary sentinel node in 143/212 (67.5%) of patients in the 2-day group and 127/175 (72.5%) in the 1-day group (P = 0.28). SLN was identified at surgery in 209/212 (98.6%) patients in the 2-day group and 174/175 (99.4%) in the 1-day group (P = 0.41). An average of 3 SLN was found at surgery in the 2-day group compared with 3.15 in the 1-day group (P = 0.43). SLN was positive for metastatic disease in 54/212 (25.5%) patients in the 2-day group compared with 40/175 (22.9%) in the 1-day group (P = 0.55). A 2-day lymphoscintigraphy protocol allows reliable detection of the SLN, of positive SLN and equivalent SLN harvest compared with a 1-day protocol. The timing of radiocolloid injection before SLNB can be left at the discretion of the surgeon.

Background: Leishmania parasites can cause visceral or cutaneous disease and are found in subtropical and tropical regions of the Old and New World. The pathology of the infection is determined by both host immune factors and species/strain differences of the parasite. Dogs represent the major reservoir of Leishmania infantum (syn. L. chagasi) and vaccines are considered the most cost-effective control tools for canine disease., Methods: Selection of immunodominant peptides was performed by Phage Display to identify sequences recognized by L. infantum naturally infected animals. Sera from Leishmania infected animals were used in the biopanning to selection of specific peptides. Serum samples from T. cruzi infected and healthy animals were used as control. After selection, synthetic peptides were produced in membrane (spot-synthesis) in soluble form and blotting and ELISA were performed for validation of serum reactivity. Selected peptide was formulated with aluminum hydroxide and liposomes and immunization was performed in BALB/c mice. Protection was determined by qPCR after challenge infection with virulent L. infantum., Results: We reported the selection of Peptide 5 through Phage Display technique and demonstrate its ability to promote a state of immunity against L. infantum infection in murine model after immunization using liposomes as vaccine carrier. Our results demonstrate that immunization with Peptide 5 when formulated with aluminum hydroxide and liposomes is immunogenic and elicited significant protection associated with the induction of mixed Th1/Th2 immune response against L. infantum infection., Conclusion: Peptide 5 is a promising vaccine candidate and the findings obtained in the present study encourage canine trials to confirm the effectiveness of a vaccine against CVL.

ELISA and RIFI are currently used for serodiagnosis of canine visceral leishmaniasis (CVL). The accuracy of these tests is controversial in endemic areas where canine infections by Trypanosoma cruzi may occur. We evaluated the usefulness of synthetic peptides that were selected through phage display technique in the serodiagnosis of CVL. Peptides were chosen based on their ability to bind to IgGs purified from infected dogs pooled sera. We selected three phage clones that reacted only with those IgGs. Peptides were synthesized, polymerized with glutaraldehyde, and used as antigens in ELISA assays. Each individual peptide or a mix of them was reactive with infected dogs serum. The assay was highly sensitive and specific when compared to soluble Leishmania antigen that showed cross-reactivity with anti-T. cruzi IgGs. Our results demonstrate that phage display technique is useful for selection of peptides that may represent valuable synthetic antigens for an improved serodiagnosis of CVL.

Phytoextraction is a potential method for cleaning Cd-polluted soils. Ligand addition to soil is expected to enhance Cd phytoextraction. However, experimental results show that this addition has contradictory effects on plant Cd uptake. A mechanistic model simulating the reaction kinetics (adsorption on solid phase, complexation in solution), transport (convection, diffusion) and root absorption (symplastic, apoplastic) of Cd and its complexes in soil was developed. This was used to calculate plant Cd uptake with and without ligand addition in a great number of combinations of soil, ligand and plant characteristics, varying the parameters within defined domains. Ligand addition generally strongly reduced hydrated Cd (Cd(2+)) concentration in soil solution through Cd complexation. Dissociation of Cd complex ([Formula: see text]) could not compensate for this reduction, which greatly lowered Cd(2+) symplastic uptake by roots. The apoplastic uptake of [Formula: see text] was not sufficient to compensate for the decrease in symplastic uptake. This explained why in the majority of the cases, ligand addition resulted in the reduction of the simulated Cd phytoextraction. A few results showed an enhanced phytoextraction in very particular conditions (strong plant transpiration with high apoplastic Cd uptake capacity), but this enhancement was very limited, making chelant-enhanced phytoextraction poorly efficient for Cd.