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A practical and effective photoredox propargylation of aldehydes promoted by 10 mol % of [Cp2TiCl2] is presented. No stoichiometric metals or scavengers are used for the process. A catalytic amount of the cheap and simply prepared organic dye 3DPAFIPN is used as the reductant for titanium. The reaction displayed a broad scope, and no traces of allenyl isomers were detected for simple propargyl bromide, whereas mixtures of propargyl and allenyl isomers were observed for substituted propargyl bromides.

The multifactorial nature of Alzheimer's disease (AD) is a reason for the lack of effective drugs as well as a basis for the development of "multi-target-directed ligands" (MTDLs). As cases increase in developing countries, there is a need of new drugs that are not only effective but also accessible. With this motivation, we report the first sustainable MTDLs, derived from cashew nutshell liquid (CNSL), an inexpensive food waste with anti-inflammatory properties. We applied a framework combination of functionalized CNSL components and well-established acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) tacrine templates. MTDLs were selected based on hepatic, neuronal, and microglial cell toxicity. Enzymatic studies disclosed potent and selective AChE/BChE inhibitors (5, 6, and 12), with subnanomolar activities. The X-ray crystal structure of 5 complexed with BChE allowed rationalizing the observed activity (0.0352 nM). Investigation in BV-2 microglial cells revealed antineuroinflammatory and neuroprotective activities for 5 and 6 (already at 0.01 mu M), confirming the design rationale.

PURPOSE The activity of androgen-deprivation therapy (ADT) in androgen receptor–positive (AR+) salivary gland carcinomas (SGCs) has been established in the past few years. Second-line treatment in castration-resistant patients is still unknown. We investigated the activity of abiraterone acetate as second-line treatment in ADT-resistant, AR+ patients with SGC. METHODS This was a single-institution phase II trial. A two-stage Simon's design was applied. The primary end point was confirmed objective response rate. Secondary end points were disease control rate, safety, progression-free survival, and overall survival. Patients were eligible when the following criteria were met: histologic diagnosis of AR-overexpressing SGC, measurable disease according to RECIST 1.1, clinical and/or radiologic progression on ADT, suppressed serum testosterone, and no limits for the number of previous chemotherapy lines. All patients received abiraterone 1 g daily plus prednisone 10 mg and luteinizing hormone-releasing hormone agonist until progression or unacceptable toxicities. RESULTS From 2015 to 2019, 24 AR+ patients with SGC (23 men; median age 65.8 years) were treated within the study. The overall response rate was 21% (5 partial responses), with a disease control rate of 62.5%. The median duration of response was 5.82 months. Median progression-free survival was 3.65 months (95% CI, 1.94 to 5.89), and median overall survival was 22.47 months (95% CI, 6.74 to not reached). Objective response to previous ADT did not correlate with the activity of abiraterone. Adverse events (AEs) were recorded in 22 cases (92%) with grade 3 AEs in six patients (25%): fatigue (two), flushing (one), supraventricular tachycardia (one), and two non–drug-related AEs. No drug-related grade 4 or 5 AEs were recorded. CONCLUSION Abiraterone plus luteinizing hormone-releasing hormone agonist is active and safe as a second-line option in AR-expressing, castration-resistant SGC.

Purpose To describe a case of congenital retinal macrovessel complicated by cystoid macular edema associated with contralateral myelinated retinal nerve fibers and retinal vascular abnormalities studied with optical coherence tomography angiography (OCTA). Methods Case report. Results A healthy 25-year-old woman with decreased vision in her right eye was found to have a congenital retinal venous macrovessel in the macula associated with cystoid edema. In the contralateral amblyopic eye, the examination revealed a tuft of myelinated retinal nerve fibers along the superotemporal vascular arcade associated with superficial vascular abnormalities. A complete multi-imaging examination was obtained, including fundus color photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT), and optical coherence tomography angiography. At 1-week follow-up, the optical coherence tomography displayed spontaneous resolution of the edema that remained stable at consecutive 1-month follow-up. Conclusion Congenital retinal macrovessels can be associated with other ocular developmental anomalies. Vascular complications can occur, leading to macular edema and retinal ischemia. Optical coherence tomography angiography can be useful for the diagnosis and follow-up of this condition.

Tetraphenylmethane appended with four pyridylpyridinium units works as a scaffold to self-assemble four ruthenium porphyrins in a tetrahedral shape-persistent giant architecture. The resulting supramolecular structure has been characterised in the solid state by X-ray single crystal analysis and in solution by various techniques. Multinuclear NMR spectroscopy confirms the 1 : 4 stoichiometry with the formation of a highly symmetric structure. The self-assembly process can be monitored by changes of the redox potentials, as well as by modifications in the visible absorption spectrum of the ruthenium porphyrin and by a complete quenching of both the bright fluorescence of the tetracationic scaffold and the weak phosphorescence of the ruthenium porphyrin. An ultrafast photoinduced electron transfer is responsible for this quenching process. The lifetime of the resulting charge separated state (800 ps) is about four times longer in the giant supramolecular structure compared to the model 1 : 1 complex formed by the ruthenium porphyrin and a single pyridylpyridinium unit. Electron delocalization over the tetrameric pyridinium structure is likely to be responsible for this effect.

Background: A limited number of studies investigating perioperative risk factors associated with emergency appendectomy in elderly patients have been published to date. Whether older age may be associated with poorer outcomes following appendectomy is still a matter of debate. The primary aim of this study was to determine the predictors of postoperative morbidity following appendectomy in patients aged ≥ 65years. Methods: Data regarding all elderly patients who underwent emergency appendectomy from January 2017 to June 2018 admitted 36 Italian surgical departments were prospectively collected and analyzed. Baseline demographics and perioperative variables were evaluated. Uni- and multivariate analyses adjusted for differences between groups were carried out to determine possible predictors of adverse outcomes after appendectomy. Results: Between January 2017 and June 2018, 135 patients aged ≥ 65years with a diagnosis of AA met the study inclusion criteria. Twenty-six patients (19.3%) were diagnosed with some type of postoperative complication. Decreasing the preoperative hemoglobin level showed a statistically significant association with postoperative complications (OR 0.77, CI 0.61–0.97, P = 0.03). Preoperative creatinine level (P = 0.02, OR 2.04, CI 1.12–3.72), and open appendectomy (P = 0.03, OR 2.67, CI 1.11–6.38) were significantly associated with postoperative morbidity. After adjustment, the only independent predictor of postoperative morbidity was preoperative creatinine level (P = 0.04, OR 2.01, CI 1.05–3.89). Conclusions: In elderly patients with AA, perioperative risk assessment in the emergency setting must be as accurate as possible to identify modifiable risk factors that can be addressed before surgery, such as preoperative hemoglobin and creatinine levels.

Pyrene-based materials have gained considerable attention as stimuli-responsive chemical sensors. We designed a polysulfurated arene system based on a tetra(phenylthio)pyrene core decorated with four carboxylic acid units. Three different regioisomers, ortho, meta and para were studied in organic and aqueous solution. These systems are soluble in water at pH≥8 due to the deprotonation of carboxylic acids. The addition of metal ions cannot only quench the fluorescence of the central pyrene core, but also control the formation of three-dimensional nanoscopic objects in a dual mode function. Several divalent metal ions were tested and compared. Addition of ethylenediaminetetraacetic acid (EDTA) disassembles the non-emissive supramolecular system and restores the initial fluorescence of the pyrene core.

α-Bisabolol (BSB) is a plant-derived sesquiterpene alcohol able to trigger regulated cell death in transformed cells, while deprived of the general toxicity in several mouse models. Here, we investigated the involvement of lysosomal and mitochondrial compartments in the cytotoxic effects of BSB, with a specific focus on the BH3-only activator protein BID. We found that BSB particularly accumulated in cancer cell lines, displaying a higher amount of lipid rafts as compared to normal blood cells. By means of western blotting and microscopy techniques, we documented rapid BSB-induced BID translocation to lysosomes and mitochondria, both of them becoming dysfunctional. Lysosomal membranes were permeabilized, thus blocking the cytoprotective autophagic flux and provoking cathepsin B leakage into the cytosol. Multiple flow cytometry-based experiments demonstrated the loss of mitochondrial membrane potential due to pore formation across the lipid bilayer. These parallel events converged on neoplastic cell death, an outcome significantly prevented by BID knockdown. Therefore, BSB promoted BID redistribution to the cell death executioner organelles, which in turn activated anti-autophagic and proapoptotic mechanisms. This is an example of how xenohormesis can be exploited to modulate basic cellular programs in cancer.

This work reports the synthesis and characterization of titanate nanotubes (TiNTs) and their use for the construction of an electrochemical sensor for lead (II) determination in water samples. TiNTs were prepared from TiO2 by a hydrothermal route at 150 ��C for 24 h in alkaline conditions. X-ray diffraction (XRD) measurements show peak enlargement and the presence of trititanate with different spaces between layers confirming the production of TiNTs of nanometric dimensions. In addition, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images demonstrated the presence of dispersed, homogenous, and nanometric tubular structure. TiNTs were used for the modification of carbon paste electrodes and evaluated for determination of lead (II) by differential pulse adsorptive stripping voltammetry (DPAdSV). Using the optimized conditions, the developed method provided a linear dynamic range (LDR) from 0.77 to 7.71 ��M and limits of detection and quantification of 0.23 and 0.77 ��M, respectively. Studies of addition and recovery in spiked water sample were performed, obtaining a recovery of 104.6%. A repeatability study resulted in a relative standard deviation of 11% for consecutive measurements. Using the same electrode, a reproducibility study provided a relative standard deviation of 3.9%.

Hemorrhage in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) may be attributed to chemotherapy and local tumor irradiation. Evidence of the relationship between hemorrhage in R/M HNSCC and targeted therapies, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) inhibitors, or immune checkpoint inhibitors, is limited. We aimed to identify epidemiological and clinical data related to the occurrence of hemorrhage in R/M HNSCC and to explore its relationship with various therapies. We describe information obtained from literature searches as well as data extracted from a commercial database and a database from the author's institution (Istituto Nazionale dei Tumori of Milan). Evidence suggests that most bleeding events in R/M HNSCC are minor. Clinical trial safety data do not identify a causal association between hemorrhage and anti‐EGFR agents or immune checkpoint inhibitors. In contrast, anti‐VEGF agents are associated with increased, and often severe/fatal, hemorrhagic complications.

Purpose: We studied the IOP-lowering effects of NCX 1741, a novel nitric oxide (NO)-donating derivative of the phosphodiesterase type-5 inhibitor, avanafil, in Cynomolgus monkey with laser-induced ...

Radioactive-iodine (RAI)-resistant differentiated thyroid cancer (DTC) patients benefit from multi-kinase inhibitors (MKIs), such as lenvatinib. Incidence of treatment-related (TR) late toxicities has been not yet described. From January 2015 to June 2019 we retrospectively reviewed clinical records of patients with RAI-resistant DTC treated with lenvatinib at Istituto Nazionale dei Tumori (Milan, Italy). New side effect of any grade, appeared after 12 months of lenvatinib, was defined as late adverse event (AE). Descriptive analyses were performed. Survival curves were estimated with Kaplan–Meier method and compared with log-rank test. Thirty-seven patients were included, 65% had ≥65 years and 68% were female. Thirty patients received lenvatinib for >12 months. Lenvatinib was started at ≤20 mg/daily in 59% of patients, 64% were ≥65 years. The frequency of late AEs was 80% and cardiovascular toxicity was the most common (57%). There was no difference in the incidence of late AEs between younger/older population (77% and 82%, respectively). Median lenvatinib treatment duration (TD) was 39.96 months (95% CI 21.64-NR): 39.96 months for patients

Click chemistry probes have improved the study of drug interactions in live cells and relevant disease models. Proper design of the probes, including the choice of the click moiety coupled to the drug, is crucial to ensure good performance and broad application. A new trans-cyclooctene derivative, amTCO, was synthesised via a novel route using a phthalimide protecting group as a built-in photosensitiser for the cyclooctene isomerization. amTCO improved the physical chemical properties of click chemistry probes compared to standard TCO moieties. An amTCO probe targeting indoleamine 2,3-dioxygenase (IDO1) was a superior tool for visualizing IDO1 and measuring the binding affinities of small molecule inhibitors to IDO1 in cells.

Due to the superior optical and electronic properties, all-inorganic perovskite materials have been widely used in optoelectronic device and energy conversion systems such as solar cells. However, photoelectrochemical devices with all-inorganic perovskite as photo-active material used in aqueous solution have been received not many attentions. In this work, the use of CsPbBr3 in photoelectrochemical system in direct contact with water is studied for the first time, considering also the post-mortem properties. Sub-micronic crystals of CsPbBr3 were synthetized by a conventional low temperature synthesis and the obtained materials were used to produce a photo-electrode for photo-electrochemical cell (PEC). The material was characterized and then tested to assess its electrochemical and photocatalysis properties. The particles showed high photocatalytic activity (more than 50% of Rhodamine degradation after 80 min) and promising photocurrent values of 11.7 µA cm−2 and 2.25 μA cm−2 in reduction and oxidation conditions respectively. The synthesis conditions assured CsPbBr3 good stability in water up to 60 min. After this time, system passes from pure CsPbBr3 to a mixture of CsPbBr3 and Cs4PbBr6 still retaining part of its photoelectrochemical activity. The results showed that CsPbBr3 has good potentiality as photo-electrode material in water-based photoelectrochemical cell for the conversion of CO2 into fuels or chemicals.

Simple, low-cost, and sensitive new platforms for electrochemical immunosensors for virus detection have been attracted attention due to the recent pandemic caused by a new type of coronavirus (SARS-CoV-2). In the present work, we report for the first time the construction of an immunosensor using a commercial 3D conductive filament of carbon black and polylactic acid (PLA) to detect Hantavirus Araucaria nucleoprotein (Np) as a proof-of-concept. The recognition biomolecule was anchored directly at the filament surface by using N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and N-Hydroxysuccinimide (EDC/NHS). Conductive and non-conductive composites of PLA were characterized using thermal gravimetric analysis (TGA), revealing around 30% w/w of carbon in the filament. Morphological features of composites were obtained from SEM and TEM measurements. FTIR measurement revealed that crosslinking agents were covalently bonded at the filament surface. Electrochemical techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used for the evaluation of each step involved in the construction of the proposed immunosensor. The results showed the potentiality of the device for the quantitative detection of Hantavirus Araucaria nucleoprotein (Np) from 30 μg mL−1 to 240 μg mL−1 with a limit of detection of 22 μg mL−1. Also, the proposed immunosensor was applied with success for virus detection in 100x diluted human serum samples. Therefore, the PLA conductive filament with carbon black is a simple and excellent platform for immunosensing, which offers naturally carboxylic groups able to anchor covalently biomolecules., Graphical abstract Image 1

The one-photon (1P) and two-photon (2P) absorption properties of three quadrupolar dyes, featuring thiophene as a donor and acceptors of varying strengths, are determined by a combination of experimental and computational methods employing the density functional theory (DFT). The emission shifts in different solvents are well reproduced by time-dependent DFT calculations with the linear response and state specific approaches in the framework of the polarizable continuum model. The calculations show that the energies of both 1P- and 2P-active states decrease with an increase of the strength of the acceptor. The 2P absorption cross-sections predicted by the response theory are accounted for by considering just one intermediate state (S1) in the sum-over-states formulation. For the chromophore featuring the stronger acceptor, the energetic positions of the 1P- and 2P-active states prevent the exploitation of the theoretically predicted very high 2P activity due to the competing 1P absorption into the S1 state.

Sara Bochicchio,1 Paolo Milani,1 Lara Enrica Urbini,1 Ennio Bulone,1 Luciana Carmassi,1 Elena Fratantonio,1 Giacomo Castegna,1 Lorenza Scotti,2 Antonella Zambon,2 Fulvio Bergamini1 1Ophthalmology Department, Istituto Auxologico Italiano, Milan, Italy; 2Statistics and Quantitative Methods Department, University of Milano-Bicocca, Milan, ItalyCorrespondence: Paolo MilaniIstituto Auxologico Italiano, Via Mercalli 30, Milan, ItalyTel +39 2 3385840232Fax +39 2 20422262Email dottpaolomilani@hotmail.comPurpose: By using optical coherence tomography angiography (OCTA), to evaluate diurnal changes of the following parameters: vessel density in the peripapillary area (PP-VD) and in the optic nerve head (ONH-VD); thickness of retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC).Methods: All prospectively enrolled participants were imaged on the same day at 8 am and 7 pm by means of the XR Avanti device with AngioVue and AngioAnalytics software (Optovue Inc., Fremont, CA, USA). Only eyes with correct automatic segmentation and good-quality images (scan quality > 7/10) were included.Results: Forty-six eyes from 28 patients with glaucoma, 53 from 31 patients with ocular hypertension, and 62 from 38 controls were assessed. The mean measurements of all parameters investigated were significantly different in the morning and in the evening values in all three groups, with lower values in glaucomatous eyes (p0.1).Conclusion: Vessel density, GCC and RNFL were stable during daytime thus corroborating the clinical relevance of OCTA regardless the time of acquisition.Keywords: glaucoma, optical coherence tomography angiography, vessel density, daily fluctuations, retinal fiber layer

This work reports for the first time the use of titanate nanotubes (TiNT) as adsorbent structure for Hg2+ ions and its use in construction of mercury-based electrodes for analytical applications. TiNTs with diameter of around 15 nm and length between 40 and 200 nm were obtained by hydrothermal alkaline synthesis and characterized by FTIR, DRX, and TEM. A carbon paste electrode modified with 15% (w/w) of TiNT was used for spontaneous mercury ions incorporation, by simply immerging in a Hg2+ solution for 120 s. “Mercury isles” were obtained by electrochemical reduction of adsorbed Hg2+ ions. Under the best optimized conditions, the proposed device was evaluated for the determination of Zn2+ ions in pharmaceutical samples. A linear relationship of anodic peak current and Zn2+ ions concentration was observed at a range of 4.0–20 µmol dm−3, with sensitivity of 0.54 μA dm3 μmol−1, limit of detection and limit of quantification of 1.2 µmol dm−3 and 4.0 µmol dm−3, respectively. Satisfactory agreement with a comparative method showed the useful application of the sensor, with the advantage of the Zn preconcentration step at open circuit potential condition. This strategy allows the use of several electrodes at the same time, which characterize this device as a feasible passive sampler.

Locally advanced stage cervical cancer diagnosed during pregnancy is a clinical challenge and requires skill in balancing maternal management, fetal care, and oncological treatment. Cisplatin has been routinely used as a first line agent for neoadjuvant chemotherapy in this situation, even though it has also recently been associated with fetal hearing loss. We report a case of stage IB3 cervical cancer diagnosed at 17 gestational weeks successfully treated with neoadjuvant chemotherapy using carboplatin and paclitaxel during pregnancy. Carboplatin is a valid alternative to cisplatin for advanced stage cervical carcinoma in a pregnant patient, in particular in view of the neonatal complications (primarily ototoxicity) that are associated with in utero cisplatin exposure.

Caffeine, the most commonly consumed psychoactive drug in the world, is readily available in dietary sources, including soft drinks, chocolate, tea and coffee. However, little is known about the neural substrates that underlie caffeine's rewarding and aversive properties and what ultimately leads us to seek or avoid caffeine consumption. Using male Wistar rats in a place conditioning procedure, we show that systemic caffeine at a low intraperitoneal dose of 2 mg/kg (or 100 µM injected directly into the rostral, but not caudal, portion of the ventral tegmental area) produced conditioned place preferences. By contrast, high doses of systemic caffeine at 10 and 30 mg/kg produced conditioned place aversions. These aversions were not recapitulated by a caffeine analog restricted to the periphery. Both caffeine reward and aversion were blocked by systemic D1-like receptor antagonism using SCH23390, while systemic D2-like receptor antagonism with eticlopride had smaller effects on caffeine motivation. Most important, we demonstrated that pharmacological blockade of dopamine receptors using α-flupenthixol injected into the nucleus accumbens shell, but not core, blocked caffeine-conditioned place preferences. Conversely, α-flupenthixol injected into the nucleus accumbens core, but not shell, blocked caffeine-conditioned place aversions. Thus, our findings reveal two dopamine-dependent and functionally dissociable mechanisms for processing caffeine motivation, which are segregated between nucleus accumbens subregions. These data provide novel evidence for the roles of the nucleus accumbens subregions in mediating approach and avoidance behaviours for caffeine.

Low-density lipoprotein (LDL) apheresis (LA) selectively eliminates lipoproteins containing apolipoprotein B 100 (ApoB100) on patients affected by severe dyslipidemia. In addition to lowering lipids, LA is thought to exert pleiotropic effects altering a number of other compounds associated with atherosclerosis, such as pro- and anti-inflammatory cytokines or pro-thrombotic factors. More knowledge needs to be gathered on the effects of LA, and particularly on its ability to modify blood components other than lipids. We performed a multiparametric assessment of the inflammatory, metabolic and proteomic profile changes after Heparin-induced lipoprotein precipitation (H.E.L.P.) apheresis on serum samples from nine dyslipidemic patients evaluating cholesterol and lipoproteins, plasma viscosity and density, metabolites, cytokines, PCSK9 levels and other proteins selectively removed after the treatment. Our results show that H.E.L.P. apheresis is effective in lowering lipoprotein and PCSK9 levels. Although not significantly, complement and inflammation-related proteins are also affected, indicating a possible transient epiphenomenon induced by the extracorporeal procedure.

The treatment of patients with recurrent and/or metastatic (R/M) salivary gland adenoid cystic carcinoma (ACC) remains an unmet need.Patients with R/M disease with a history of clinical or symptomatic disease progression within 6 months and a maximum of 1 previous line of chemotherapy or a multiple kinase inhibitor received oral lenvatinib at a dose of 24 mg/day. The primary endpoint was the objective response rate; secondary endpoints included quality of life (QOL) (according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items [EORTC QLQ-C30] and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Module Head and Neck Module [EORTC QLQ-HN35]), progression-free survival and overall survival, duration of response, and toxicities.Twenty-eight patients with R/M ACC were enrolled. Among 26 evaluable patients, 3 partial responses (11.5%) were reported. Target lesion reductions between 23% to 28% were observed in 4 of 20 patients with stable disease. Treatment-related adverse events were frequent (all grades, 96%; grade≥3 in 50% of cases according to version 4.03 of the National Cancer Institute Common Terminology Criteria for Adverse Events). The dose of lenvatinib was reduced in 24 patients, whereas in 21 patients the dose was reduced within the first 12 weeks and 4 patients maintained the full dose throughout treatment. The QOL deteriorated between baseline and 6 months with regard to Fatigue and Dry Mouth. There was no evidence of changes in Swallowing and Physical Functioning. At a median follow-up of 29 months, 2 patients remained on treatment, 10 patients were off protocol for disease progression and were alive with disease, and 14 patients had died of disease progression. The median overall survival, progression-free survival, and duration of response were 27 months, 9.1 months, and 3.1 months, respectively.Lenvatinib appears to have modest activity in ACC. Toxicities are common but manageable and QOL was found to deteriorate in some domains.

Monitoring drug-target interactions with methods such as the cellular thermal-shift assay (CETSA) is well established for simple cell systems but remains challenging in vivo. Here we introduce tissue thermal proteome profiling (tissue-TPP), which measures binding of small-molecule drugs to proteins in tissue samples from drug-treated animals by detecting changes in protein thermal stability using quantitative mass spectrometry. We report organ-specific, proteome-wide thermal stability maps and derive target profiles of the non-covalent histone deacetylase inhibitor panobinostat in rat liver, lung, kidney and spleen and of the B-Raf inhibitor vemurafenib in mouse testis. In addition, we devised blood-CETSA and blood-TPP and applied it to measure target and off-target engagement of panobinostat and the BET family inhibitor JQ1 directly in whole blood. Blood-TPP analysis of panobinostat confirmed its binding to known targets and also revealed thermal stabilization of the zinc-finger transcription factor ZNF512. These methods will help to elucidate the mechanisms of drug action in vivo.

This work describes the construction and evaluation of carbon fiber ultramicroelectrodes (CF-UMEs) in the voltammetric estimation of the antioxidant capacity of wine and grape samples based on caffeic acid (HCAF) oxidation. For this, lab-made CF-UMEs were constructed using an arrangement of six carbon fibers (7 μm diameters individual) assembled in a glass capillary, and caffeic acid (HCAF) was used as a standard solution. By using the most straightforward 2-electrode cell arrangement (the CF-UME as a working electrode and Ag/AgCl as a reference/auxiliary electrode), voltammetric measurements of a 1.0 mmol L-1 HCAF solution were done in the absence of a supporting electrolyte. A sigmoidal voltammetric profile was observed in CF-UMEs caused by a more effective mass transport by radial diffusion, which leads to a rapid formation of the diffusion layer. Reproducibility studies for different 6-fiber electrodes manually constructed in different batches showed an RSD of less than 5%. For the same electrode surface, a variation of 2.7% was observed. Under optimized conditions, a linear relationship between anodic peak current and HCAF concentration from 3.0 to 500 μmol L-1 with a sensitivity of 12 μA L mol-1 was reached. The limits of detection (LOD) and quantification (LOQ) were calculated to be 0.41 and 1.26 μmol L-1, respectively. The proposed electrochemical method was applied in the estimation of the antioxidant capacity in three different wine samples as well as in green and red grapes. Concordant and satisfactory results by comparison with a proper method were obtained, which suggests that the proposed sensor can be successfully applied for direct analysis of wine and grape samples by estimation of HCAF content.

Surface properties of carbon nanotubes in electrochemical sensors can be dramatically altered depending on chemical groups and structural defects present on the surface. The effect of oxidation on structural integrity of multiwalled carbon nanotubes through acidic (nitric/sulfuric acids) and basic (sodium hydroxide) agents has been studied. Chemical modifications of carbon nanotubes structures were evaluated by Raman, Fourier transform infrared spectroscopy and transmission electronic microscopy. Furthermore, these materials were used to construct sensors for electrochemical determination of pesticide methyl parathion (MP). Under optimized conditions, a calibration curve was obtained for MP determination employing a glassy carbon electrode modified with acidic treated and basic treated carbon nanotubes which showed a linear response ranging from 1.0 × 10–7 to 3.4 × 10–5 M with limits of detection of 3.3 × 10–8 and 3.5 ×10–8 M, respectively. Analytical performance of the electrodes showed similar voltammetric behavior providing good sensitivity for the determination of methyl parathion.

Optimization of a lead series of PI3Kδ inhibitors based on a dihydroisobenzofuran core led to the identification of potent, orally bioavailable compound 19. Selectivity profiling of compound 19 showed similar potency for class III PI3K, Vps34, and PI3Kδ, and compound 19 was not well-tolerated in a 7-day rat toxicity study. Structure-based design led to an improvement in selectivity for PI3Kδ over Vps34 and, a focus on oral phramacokinetics properties resulted in the discovery of compound 41, which showed improved toxicological outcomes at similar exposure levels to compound 19.

This work describes the first method using biochar (BC) as carbonaceous platform for immunoassay application. BC is a highly functionalized material obtained through biomass pyrolysis under controlled conditions. Due to the highly functionalized surface, covalent binding between BC and biomolecules can be performed by EDC/NHS conjugation. The application of the modified electrode was done with Hantavirus, that are etiologic agents mainly transmitted by wild rodents. Among its pathologies Hantavirus Cardiopulmonary Syndrome (HCPS) arises at Americas, caused by Hantavirus Araucaria and reaches 40% lethality. The diagnostic is based on the presence of specific hantavirus nucleoprotein (Np), under viremic condition or IgG2b antibodies (Ab), during first symptoms. The results presented a device sensitivity of 5.28 μA dec-1 and a LOD of 0.14 ng mL-1 to the Np detection, ranging from 5.0 ng mL-1 to 1.0 μg mL-1, the Ab detection works as qualitative type sensor above 200 ng mL-1. Both sensors were evaluated its selectivity and serum samples; selectivity against Gumboro disease, VP2 protein, and antibody IgG2a against Yellow fever disease (YF), respectively. So, the devices here proposed are promising tool suitable for both rodent and human hantavirus clinical surveys.

International audience; The photoelectrochemical charge-transfer process occurring at semiconductor surfaces has important implications in the fields of solar fuels and biodetection. Usually, physical light sources located outside the liquid phase, such as a solar simulator, a light-emitting diode (LED), or a laser, are used for photoelectrochemical studies. Here, we report inducing photoelectrochemistry using an electrochemical source of light, that is, the electrochemiluminescence (ECL) emitted by a model co-reactant system. Results reveal that the ECL illumination can activate several semiconductor (SC) photoelectrodes based on n-type Si, n-type GaAs, and p-type Si. We demonstrate that this emitter-receiver concept, based on dual-light conversion, enables photoelectrochemical charge transfer at the solid/liquid interface, which correlates with the ECL intensity. The singularities of this concept lie in the fact that light emission and collection both occur in the liquid phase, that ECL is an easily miniaturizable photon source, and that the SC/liquid junction can be easily implemented. This approach may open perspectives for remote ECL detection strategies and original photoelectrochemical analytical systems.

New Plant Breeding Techniques (NPBTs) protocols have been developed to produce new grape varieties with improved quantitative and qualitative characteristics. Reliable transformation protocols for grapes are based on the generation/induction of embryogenic callus cells that are then transformed. Varieties such as Italia have proven to be very recalcitrant to regeneration via somatic embryogenesis. In this work, the development of a protocol for improved production of embryogenic calluses is described. Two sterilization protocols were tested: (a) a lower active chlorine concentration for a longer time (LS), and (b) a higher chlorine concentration for a shorter time (HS), in combination with the absence or presence of citric acid in the growing substrate in the first growth media. The embryogenic calluses formation in Chardonnay, a cv. with a high embryogenic response, was significantly higher in presence of citric acid in the initial growing substrate regardless of the sterilization protocol. In Aglianico, a cv. with a lower embryogenic response, no significant differences were observed. Instead, in a recalcitrant cv. as Italia, we obtained a 13-fold increase in embryogenic calluses formation performing sterilization of flowers with the HS protocol compared to LS.

We have investigated motility in breast cancer cell lines in association with the expression of Transglutaminase type 2 (TG2) as well as upon the administration of Doxorubicin (Dox), an active cytotoxic agent that is employed in chemotherapy. The exposure of MCF-7 cells to the drug increased TG2 levels, triggering epithelial–mesenchymal transition (EMT), thereby supporting cell motility. The effects of Dox on the movement of MCF-7 cells were counteracted by treatment with NC9, a TG2 inhibitor, which induced morphological changes and also reduced the migration of MDA-MB-231 cells exhibiting high levels of TG2. The physical association of TG2 with the cytoskeletal component vimentin appeared pivotal both in drug-treated MCF-7 and in MDA-MB-231 cells and seemed to be independent of the catalytic activity of TG2. NC9 altered the subcellular distribution of TG2 and, consequently, the co-localization of TG2 with vimentin. Furthermore, NC9 induced a nuclear accumulation of TG2 as a prelude to TG2-dependent gene expression modifications. Since enzyme activity can affect both motility and nuclear functions, targeting of this protein could represent a method to improve therapeutic interventions in breast tumors, particularly those to control progression and to limit drug resistance.

This work presents a feasible process for preparation screen-printed electrode (SPE) using a lab-made conductive ink based on cellulose acetate (CAc) and graphite powder (GP) printed on polyvinyl chloride (PVC) sheet. The CAc present in the composition of this SPE is a binding agent for conductive inks with GP, which are relatively low-cost and easily obtainable materials, compared to other similar commercial sensors. The SPE was evaluated through cyclic voltammetry (CV) using an equimolar [Fe(CN)6]3-/4− solution as a redox probe to find an adequate ink composition. Electrode surface was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). To show the analytical potential of SPE proposed it was used for Levodopa (L-dopa) determination. L-dopa is a drug frequently used to reduce the symptoms of Parkinson's disease. The GP-CAc/PVC electrode was evaluated for the determination of L-dopa under square wave voltammetric (SWV) conditions. The electrode presented a linear dynamic range (LDR) from 8.00 to 100 µmol L−1 and a limit of detection (LOD) of 0.06 µmol L−1. As a proof-of-concept, the proposed electrode was used to quantify L-dopa in drug samples as an alternative tool for quality control tests, being applied to two commercial drugs. The electrode construction strategy proved to be reproducible with an analytical performance comparable to other similar electrodes reported in the literature.