Regioselective Synthesis of Hamilton-Receptor-Fullerene Oligo-Adducts for the Supramolecular Binding of Cyanuric Derivatives.

A new concept for the regioselective synthesis of Hamilton-receptor and cyanurate-functionalized oligo adducts of the fullerene C60 was developed. Based on an in-situ deprotection and click-post-functionalization approach with novel azido precursors, the corresponding fullerene hexakis-adducts with octahedral addition patterns and up to twelve Hamilton-receptor/cyanurate moieties surrounding the fullerene sphere were synthesized. The versatility of this approach was further demonstrated by the synthesis of Hamilton-receptor/cyanurate functionalized fullerene mono-adducts, which are not accessible by direct cyclopropanation. Several fullerene target compounds were purified by simple washing procedures of the solid crude reaction mixture without the need for chromatography. The resulting fullerene mono- and hexakis-adducts were fully characterized and their supramolecular properties were investigated by NMR-spectroscopy and isothermal titration calorimetry (ITC).

Integrated System Built for Small-Molecule Semiconductors via High-Throughput Approaches.

High-throughput synthesis of solution-processable structurally variable small-molecule semiconductors is both an opportunity and a challenge. A large number of diverse molecules provide a possibility for quick material discovery and machine learning based on experimental data. However, the diversity of the molecular structure leads to the complexity of molecular properties, such as solubility, polarity, and crystallinity, which poses great challenges to solution processing and purification. Here, we first report an integrated system for the high-throughput synthesis, purification, and characterization of molecules with a large variety. Based on the principle "Like dissolves like," we combine theoretical calculations and a robotic platform to accelerate the purification of those molecules. With this platform, a material library containing 125 molecules and their optical-electronic properties was built within a timeframe of weeks. More importantly, the high repeatability of recrystallization we design is a reliable approach to further upgrading and industrial production.

3D-Shaped Binders of Unfolded Proteins Inducing Cancer Cell-Specific Endoplasmic Reticulum Stress In Vitro and In Vivo.

The amount of unfolded proteins is increased in cancer cells, leading to endoplasmic reticulum (ER) stress. Therefore, cancer cells are sensitive to drugs capable of further enhancing ER stress. Examples of such drugs include the clinically approved proteosome inhibitors bortezomib and carfilzomib. Unfortunately, the known ER stress inducers exhibit dose-limiting side effects that justify the search for better, more cancer-specific drugs of this type. Herein, we report on FeC 2, which binds to unfolded proteins prevents their further processing, thereby leading to ER stress and ROS increase in cancer cells, but not in normal cells. FeC 2 exhibits low micromolar toxicity toward human acute promyelocytic leukemia HL-60, Burkitt's lymphoma BL-2, T-cell leukemia Jurkat, ovarian carcinoma A2780, lung cancer SK-MES-1, and murine lung cancer LLC1 cells. Due to the cancer-specific mode of action, 2 is not toxic in vivo up to the dose of 147 mg/kg, does not affect normal blood and bone marrow cells at the therapeutically active dose, but strongly suppresses both primary tumor growth (confirmed in Nemeth-Kellner lymphoma and LLC1 lung cancer models of murine tumor) and spreading of metastases (LLC1).

Sugar-Bridged Fullerene Dumbbells and Their Interaction with the [10]Cycloparaphenylene Nanoring.

The synthesis and characterization of four dumbbell-shaped fullerene molecules connected by isosorbide and isomannide moieties is presented. Additionally, their electrochemical behavior and their ability to form complexes with [10]cycloparaphenylene ([10]CPP) were investigated. The cyclic voltammetry (CV) results of the fullerene dumbbells demonstrate a high electron affinity, indicating their strong interaction with electron-donating counterparts such as carbon nanorings, which possess complementary charge and shape properties. To study the thermodynamic and kinetic parameters of complexation, isothermal titration calorimetry (ITC) was employed. NMR titration experiments provided further insights into the binding stoichiometries. Two distinct approaches were utilized to create bridged structures: one based on cyclopropane and the other based on furan. Regardless of the type of linker used, all derivatives formed conventional 2 : 1 complexes denoted as [10]CPP2 ⊃C60derivative . However, the methano-dumbbell molecules exhibited distinct binding behavior, resulting in the formation of mono- and bis-pseudorotaxanes, as well as oligomers (polymers). The formation of linear polymers holds significant potential for applications in solar energy conversion processes.

An Indacenopicene-based Buckybowl Catcher for Recognition of Fullerenes.

A novel buckybowl catcher with an extended π-surface has been synthesized via cross-coupling of two bowl shaped bromoindacenopicene moieties with a tolyl linker. The obtained catcher has been unambiguously characterized by 2D-NMR and mass spectrometry. DFT calculations indicate that the curved shape of the receptor moieties is favourable for binding fullerenes. Effective binding was confirmed for interactions with C60 and C70 utilizing NMR spectroscopy and isothermal titration calorimetry (ITC). The resulting binding values show a higher affinity of the catcher towards C70 over C60 . The designed catcher demonstrated the fundamental possibility of creating sensors for spherical aromaticity.

An Indacenopicene-based Buckybowl Catcher for Recognition of Fullerenes.

Invited for the cover of this issue are the groups of Alexander S. Oshchepkov, Konstantin Y. Amsharov, and M. Eugenia Pérez-Ojeda at the Max Planck Institute for the Science of Light, Martin-Luther-University Halle-Wittenberg and Friedrich-Alexander-Universität Erlangen-Nürnberg, respectively. The image depicts a buckybowl catcher carefully framing the C70 fullerene which is associated with miraculous, marvellous Fabergé artworks. Read the full text of the article at 10.1002/chem.202302778.

Two Rings Around One Ball: Stability and Charge Localization of [1 : 1] and [2 : 1] Complex Ions of [10]CPP and C60/70 [ *].

We investigate the gas-phase chemistry of noncovalent complexes of [10]cycloparaphenylene ([10]CPP) with C60 and C70 by means of atmospheric pressure photoionization and electrospray ionization mass spectrometry. The literature-known [1 : 1] complexes, namely [10]CPP⊃C60 and [10]CPP⊃C70 , are observed as radical cations and anions. Their stability and charge distribution are studied using energy-resolved collision-induced dissociation (ER-CID). These measurements reveal that complexes with a C70 core exhibit a greater stability and, on the other hand, that the radical cations are more stable than the respective radical anions. Regarding the charge distribution, in anionic complexes charges are exclusively located on C60 or C70 , while the charges reside on [10]CPP in the case of cationic complexes. [2 : 1] complexes of the ([10]CPP2 ⊃C60/70 )+ ⋅/- ⋅ type are observed for the first time as isolated solitary gas-phase species. Here, C60 -based [2 : 1] complexes are less stable than the respective C70 analogues. By virtue of the high stability of cationic [1 : 1] complexes, [2 : 1] complexes show a strongly reduced stability of the radical cations. DFT analyses of the minimum geometries as well as molecular dynamics calculations support the experimental data. Furthermore, our novel gas-phase [2 : 1] complexes are also found in 1,2-dichlorobenzene. Insights into the thermodynamic parameters of the binding process as well as the species distribution are derived from isothermal titration calorimetry (ITC) measurements.

Cultural influence on the expression of labour-associated pain.

BACKGROUND: Every woman expresses pain differently during birth since it depends on a multitude of predictive factors. The medical care received, companionship during birth, cultural background and language barriers of the women in labour can influence on the expression of pain. This study aims to evaluate the expression of pain during birth and its associated factors in women treated in a Spanish border town. METHODS: The study included 246 women in labour. The expression of pain during labour was evaluated using the validated ESVADOPA scale. A descriptive analysis and association study were performed between cultural identity and dimensions of the scale. Multiple linear regression models were performed to assess the association between cultural identity, origin, language barrier, and companionship during labour. RESULTS: The women included in the study comprised 68.7% Berbers, 71.5% Muslims and 82.1% were accompanied during labour. An association between cultural identity and greater body expression of pain (p = 0.020; Cramer's V = 0.163) in addition to its verbal expression was found during the latent phase of labour, (p = 0.028; Cramer's V = 0.159). During the active phase of labour, cultural identity was associated with pain expression through greater body response, verbal expression, expression of the facial muscles, anxiety, inability to relax and vegetative symptoms. The different factors studied that had a predictive value were companionship (p = 0.027) during the latent phase of labour and Berber origin (p = 0.000), language barrier (p = 0.014) and companionship (p = 0.005) during the active phase of labour. The models designed predict pain expression in the latent phase by companionship and type of companionship (ß = 1.483; 95%CI = 0.459-2.506, ß = 0.238; 95%CI = 0.029-0. 448, respectively), and in the active phase by background, language barrier and companionship (ß = 0.728; 95%CI = 0.258-1.198, ß = 0.738; 95%CI = 0.150-1.326, ß = 1.888; 95%CI = 0.984-2.791, respectively). CONCLUSION: Culture, origin, language barrier and companionship during labour influences the manner in which women in labour express their pain. An understanding of this may help midwives correctly interpret the signs of pain expression and be able to offer the appropriate assistance depending on a woman's particular characteristics. There is a clear need for new models of maternity care that will take the cultural and language characteristics of women in labour into consideration.

Carbon Nano-onions: Potassium Intercalation and Reductive Covalent Functionalization.

Herein we report the synthesis of covalently functionalized carbon nano-onions (CNOs) via a reductive approach using unprecedented alkali-metal CNO intercalation compounds. For the first time, an in situ Raman study of the controlled intercalation process with potassium has been carried out revealing a Fano resonance in highly doped CNOs. The intercalation was further confirmed by electron energy loss spectroscopy and X-ray diffraction. Moreover, the experimental results have been rationalized with DFT calculations. Covalently functionalized CNO derivatives were synthesized by using phenyl iodide and n-hexyl iodide as electrophiles in model nucleophilic substitution reactions. The functionalized CNOs were exhaustively characterized by statistical Raman spectroscopy, thermogravimetric analysis coupled with gas chromatography and mass spectrometry, dynamic light scattering, UV-vis, and ATR-FTIR spectroscopies. This work provides important insights into the understanding of the basic principles of reductive CNOs functionalization and will pave the way for the use of CNOs in a wide range of potential applications, such as energy storage, photovoltaics, or molecular electronics.

Pathological conditions of the sentinel bivalve, the little mussel Brachidontes rodriguezii, from contaminated intertidal sites in the Southwestern Atlantic coast.

A survey of pathological conditions affecting the natural beds of the dominant bivalve species of the intertidal rocky coasts of the Southern Atlantic Ocean, was performed. Samples of the little mussel (n = 992), Brachidontes rodriguezii, which is considered a sentinel species, were collected from seven sites that present different anthropogenic activity (low anthropogenic activity, harbor, and sewage waste) along the Argentinean coast, and processed by standard histological techniques. Our results showed for the first time in a B. rodriguezii population from Mar del Plata harbor a bacterium causing cellular lysis of the spermatogenic cells (6.5% of prevalence) and in a population from Villa Gesell, a site with low anthropogenic activity, one little mussel presented cytoplasmic vacuoles in the oocytes's cytoplasm similar to a microsporidian (0.2% of prevalence). A ciliated protozoan parasitizing the cytoplasm of the epithelial digestive tubules and larval stages of two different digenean parasites, was found infecting the little mussel from both contaminated and uncontaminated sites. Sporocysts of the family Bucephalidae invaded the gonad, causing severe gonadal damage including castration, and gymnophallid metacercariae located between the mantle and shell or embedded in the mantle tissues, occupied the gonadal space. In Punta Carballido, a site located next to a sewage outfall, the highest prevalence of infection was found, for the ciliated protozoan in the digestive tubules (5.1%) and for the digenean parasites (bucephalid sporocyst 24.4%, and gymnophallid metacercariae 50%). Moreover, we found a positive correlation between shell length and overall prevalence of parasites.

Selenium, a dietary-antioxidant with cardioprotective effects, prevents the impairments in heart rate and systolic blood pressure in adolescent rats exposed to binge drinking treatment.

BACKGROUND: Binge drinking (BD) during adolescence is related to cardiovascular alterations. Selenium (Se) is an essential trace element with antioxidant, anti-inflammatory and antiapoptotic properties, essential for correct heart function. OBJECTIVES: To study the protective cardiovascular effects of selenium in adolescent rats exposed to a BD-like procedure. METHODS: 32 adolescent male rats exposed to an intraperitoneally BD-like model or not, and supplemented with 0.4ppm of selenite or not, were divided into 4 groups: control, alcohol, control-selenium and alcohol-selenium. Blood pressure and heart rate (HR) were determined after experimentation. Se deposits, oxidative balance and the expression of glutathione peroxidases (GPxs), NF-kB and caspase-3 were measured in the heart. Also, DNA instability in rat lymphocytes and serum vascular markers were determined. Statistical analysis was performed with the ANOVA model. RESULTS: The BD-like model depleted Se heart deposits (p < .01), decreased GPx activity (p < .01) and GPx1 (p < .001) and GPx4 (p < .05) expression, increased NF-kB (p < .01), caspase-3 (p < .001) expression, and generated oxidation in myocytes. Outside the heart, the BD-like model caused double-strand breaks in lymphocyte DNA and increased all the vascular markers measured. These cardiovascular alterations were related to higher systolic (p < .001) and diastolic (p < .05) blood pressure and HR (p < .05). In the heart, Se supplementation in BD-exposed rats significantly increased Se deposits (p < .001) and improved oxidative balance and vascular damage, including increased GPxs and decreased NF-kB and caspase-3 activation, consequently decreasing systolic (p < .05) blood pressure and HR (p < .01). CONCLUSIONS: Se supplementation presents cardioprotective effects since it reversed HR and systolic blood pressure observed in BD-exposed adolescent rats.

Fullerene Building Blocks with Tailor-Made Solubility and New Insights into Their Hierarchical Self-Assembly.

Herein, the synthesis of fullerene derivatives with adjustable polarities and lyotropic aggregation properties is reported. The polarity range spans from superhydrophobic to hydrophilic, while simultaneously providing a further reactive position with a view to graft them onto other materials. The synthetic strategy relies on a selective protection with an isoxazoline moiety. The remaining octahedral positions were further functionalized with the desired groups to tune their solubility, yielding mixed [5:1] hexakisadducts. The subsequent deprotection by clean photolytic reaction led to fullerene pentakisadducts with an incomplete octahedral addition pattern, which are useful forerunners for the synthesis of building blocks. Their hydrophobic/hydrophilic behavior has been characterized both in solution and surface through octanol/water partition coefficients (log P) and contact angle measurements. Furthermore, these derivatives can form supramolecular constructions which have been studied by dynamic light scattering (DLS) and cryo-TEM.

Biological implications of selenium in adolescent rats exposed to binge drinking: Oxidative, immunologic and apoptotic balance.

Alcohol intermittent binge drinking (BD) during adolescence decreases the levels of selenium (Se), a trace element that plays a key biological role against oxidative damage in hepatocytes through different selenoproteins such as the antioxidant enzymes glutathione peroxidases (GPx1 and Gpx4) and selenoprotein P (SelP). In this context, it has been found that GPx4 has an essential antioxidant role in mitochondria modulating the apoptosis and NF-kB activation (a factor intimately related to apoptosis and immune function). To further investigate the effectiveness of selenium supplementation in oxidative balance, inflammation and apoptosis, the present study examined the protective effects of 0.4ppm of dietary selenite administrated to adolescent rats exposed to BD. BD consumption depleted Se deposits in all the tissues studied. In liver, GPx1 activity and expression were decreased leading to protein and lipid hepatic oxidation. Moreover GPx4 and NF-kB expression were also decreased in liver, coinciding with an increase in caspase-3 expression. This hepatic profile caused general liver damage as shown the increased serum transaminases ratio AST/ALT. Proinflammatory serum citokines and chemocines were decreased. Se supplementation therapy used restored all these values, even AST levels. These findings suggest for first time that Se supplementation is a good strategy against BD liver damage during adolescence, since it increases GPx1 and GPx4 expression and avoids NF-kB downregulation and caspase-3 upregulation, leading to a better oxidative, inflammatory and apoptotic liver profile. The therapy proposed could be considered to have a great biological efficacy and to be suitable for BD exposed teenagers in order to avoid future hepatic complications.

Metabolic syndrome and selenium during gestation and lactation.

PURPOSE: Selenium (Se) has a dual role in metabolic syndrome (MS) development as it has an antioxidant action against both "good" and "bad" reactive oxygen species. This study evaluates Se body profile in dams which present MS during gestation and lactation, in order to elucidate a normal dietary Se's implication in this pathology. METHOD: Rats were randomized into control (C) and fructose (F) groups. The rich fructose diet (65 %) during gestation and lactation periods induced MS in dams. Se body distribution was determined by atomic absorption spectrophotometry, and the hepatic activity of the four antioxidant enzymes and the bimolecular oxidation were determined by spectrophotometry. The cardiac activity was monitored using the indirect tail occlusion method. Lipid and glucidic profile was also analyzed. RESULTS: Despite the fact that the diet supplied has 0.1 ppm of Se, the minimal dietary requirement for rats, F dams ate less amount of food, and therefore, they had lower Se retention. However, they had normal levels of Se in serum and milk. Dams with MS had Se depletion in heart and muscle joint to hypertension and a lower heart rate, and Se repletion in liver and kidney. Despite the increase in hepatic glutathione peroxidase (GPx) and catalase activity found, lipid oxidation occurred-probably because superoxide dismutase activity was diminished. In heart, the activity and expression of the selenoprotein GPx1 were decreased. CONCLUSION: With these results, it is not possible to elucidate whether a dietary Se supplementation or a Se-restricted diet are good for MS; because despite the fact that GPx activity is increased in liver, it is also found, for the first time, that heart Se deposits are significantly decreased during MS.

The Benefits of Administering Folic Acid in Order to Combat the Oxidative Damage Caused by Binge Drinking in Adolescent Rats.

AIMS: An important mechanism in alcohol-induced injury is biomolecular oxidative damage. Folic acid is supplied to chronic alcoholic patients in order to prevent this situation, as this is the main vitamin deficiency that they suffer from. Acute alcohol exposure, such as binge drinking, is one of the most widespread ethanol consumption models practiced by adolescents. However, there is no evidence of folic acid body profiles after this pattern of consumption. METHODS: Four groups of adolescent rats were used: control, alcohol (exposed to intraperitoneal binge drinking), control folic acid-supplemented group and alcohol folic acid-supplemented group. Folic acid levels, protein, lipid and DNA oxidative damage in serum, and liver glutathione (GSH) and reduced/oxidized glutathione ratio (GSH/GSSG) were measured. RESULTS: Binge-drinking rats had higher lipids and DNA oxidation levels. They also had lower hepatic GSH levels and GSH/GSSG ratio. Folic acid supplementation to binge-drinking rats does not change the serum protein oxidation but decreases lipid and DNA oxidation. Finally, GSH increased to control levels with folic acid supplementation. CONCLUSION: Folic acid supplementation is an economic and efficient therapy against the oxidative damage in lipids and mainly in DNA stability caused by binge drinking during adolescence. It has also been demonstrated that folic acid increases GSH levels, improving the antioxidant status and revealing a hepatoprotective effect during binge drinking.

Translocation and functional analysis of Pseudomonas savastanoi pv. savastanoi NCPPB 3335 type III secretion system effectors reveals two novel effector families of the Pseudomonas syringae complex.

Pseudomonas savastanoi pv. savastanoi NCPPB 3335 causes olive knot disease and is a model pathogen for exploring bacterial infection of woody hosts. The type III secretion system (T3SS) effector repertoire of this strain includes 31 effector candidates plus two novel candidates identified in this study which have not been reported to translocate into plant cells. In this work, we demonstrate the delivery of seven NCPPB 3335 effectors into Nicotiana tabacum leaves, including three proteins from two novel families of the P. syringae complex effector super-repertoire (HopBK and HopBL), one of which comprises two proteins (HopBL1 and HopBL2) that harbor a SUMO protease domain. When delivered by P. fluorescens heterologously expressing a P. syringae T3SS, all seven effectors were found to suppress the production of defense-associated reactive oxygen species. Moreover, six of these effectors, including the truncated versions of HopAA1 and HopAZ1 encoded by NCPPB 3335, suppressed callose deposition. The expression of HopAZ1 and HopBL1 by functionally effectorless P. syringae pv. tomato DC3000D28E inhibited the hypersensitive response in tobacco and, additionally, expression of HopBL2 by this strain significantly increased its competitiveness in N. benthamiana. DNA sequences encoding HopBL1 and HopBL2 were uniquely detected in a collection of 31 P. savastanoi pv. savastanoi strains and other P. syringae strains isolated from woody hosts, suggesting a relevant role of these two effectors in bacterial interactions with olive and other woody plants.

Concordance between freehand SPECT and conventional scintigraphy for sentinel lymph node detection in breast cancer.

INTRODUCTION: Freehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning. The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). MATERIALS AND METHODS: 100 patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 60-90min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. RESULTS: The observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). CONCLUSION: Freehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.

Role of selenium and glutathione peroxidase on development, growth, and oxidative balance in rat offspring.

Selenium (Se), an essential trace metal, is important in both growth and reproduction and is the constituent of different selenoproteins. The glutathione peroxidase (GPx) family is the most studied as it prevents oxidative stress. Liver oxidation is considered as another mechanism involved in low birth weight. Therefore, in order to ascertain whether GPx is related to the effects of Se on growth during gestation and lactation, three groups of rat pups were used: control, Se deficient (SD), and Se supplemented (SS). Morphological parameters and reproductive indices were evaluated. Hepatic Se levels were measured by graphite furnace atomic absorption while spectrophotometry was used for activity of antioxidant enzymes and oxidative stress markers in liver and western blotting for expression of hepatic GPx1 and GPx4. The SD diet increased mortality at birth; decreased viability and survival indices; and stunted growth, length, and liver development in offspring, thus decreasing hepatic Se levels, GPx, glutathione reductase, and catalase activities, while increasing superoxide dismutase activity and protein oxidation. The SS diet counteracted all the above results. GPx1 expression was heavily regulated by Se dietary intake; however, although Se dietary deficiency reduced GPx4 expression, this decrease was not as pronounced. Therefore, it can be concluded that Se dietary intake is intimately related to growth, length, and directly regulating GPx activity primarily via GPx1 and secondly to GPx4, thus affecting liver oxidation and development. These results suggest that if risk of uterine growth retardation is suspected, or if a neonate with low birth weight presents with signs of liver oxidation, it may be beneficial to know about Se status.