From a Medicinal Mushroom Blend a Direct Anticancer Effect on Triple-Negative Breast Cancer: A Preclinical Study on Lung Metastases

Bioactive metabolites isolated from medicinal mushrooms (MM) used as supportive treatment in conventional oncology have recently gained interest. Acting as anticancer agents, they interfere with tumor cells and microenvironment (TME), disturbing cancer development/progression. Nonetheless, their action mechanisms still need to be elucidated. Recently, using a 4T1 triple-negative mouse BC model, we demonstrated that supplementation with Micotherapy U-Care, a MM blend, produced a striking reduction of lung metastases density/number, paralleled by decreased inflammation and oxidative stress both in TME and metastases, together with QoL amelioration. We hypothesized that these effects could be due to either a direct anticancer effect and/or to a secondary/indirect impact of Micotherapy U-Care on systemic inflammation/immunomodulation. To address this question, we presently focused on apoptosis/proliferation, investigating specific molecules, i.e., PARP1, p53, BAX, Bcl2, and PCNA, whose critical role in BC is well recognized. We revealed that Micotherapy U-Care is effective to influence balance between cell death and proliferation, which appeared strictly interconnected and inversely related (p53/Bax vs. Bcl2/PARP1/PCNA expression trends). MM blend displayed a direct effect, with different efficacy extent on cancer cells and TME, forcing tumor cells to apoptosis. Yet again, this study supports the potential of MM extracts, as adjuvant supplement in the TNBC management.     

Laquinimod Modulates Human Astrocyte Function and Dampens Astrocyte-Induced Neurotoxicity during Inflammation

Astrocytes greatly participate to inflammatory and neurotoxic reactions occurring in neurodegenerative diseases and are valuable pharmacological targets to support neuroprotection. Here we used human astrocytes generated from reprogrammed fibroblasts as a cellular model to study the effect of the compound Laquinimod and its active metabolite de-Laquinimod on astrocyte functions and the astrocyte–neuron interaction. We show that human iAstrocytes expressed the receptor for the inflammatory mediator IL1 and responded to it via nuclear translocation of NFκB, an event that did not occur if cells were treated with Laquinimod, indicating a direct anti-inflammatory activity of the drug on the human astrocyte. Similarly, while exposure to IL1 downregulated glial glutamate transporters GLAST and GLT1, treatment with Laquinimod supported maintenance of physiological levels of these proteins despite the inflammatory milieu. Laquinimod also induced nuclear translocation of the aryl hydrocarbon receptor (AHR), suggesting that drug action was mediated by activation of the AHR pathway. However, the drug was effective despite AHR inhibition via CH223191, indicating that AHR signaling in the astrocyte is dispensable for drug responses. Finally, in vitro experiments with rat spinal neurons showed that laquinimod did not exert neuroprotection directly on the neuron but dampened astrocyte-induced neurodegeneration. Our findings indicate that fibroblast-derived human astrocytes represent a suitable model to study astrocyte–neuron crosstalk and demonstrate indirect, partial neuroprotective efficacy for laquinimod.     

An Autonomous Chemical Robot Discovers the Rules of Inorganic Coordination Chemistry without Prior Knowledge

We present a chemical discovery robot for the efficient and reliable discovery of supramolecular architectures through the exploration of a huge reaction space exceeding ten billion combinations. The system was designed to search for areas of reactivity found through autonomous selection of the reagent types, amounts, and reaction conditions aiming for combinations that are reactive. The process consists of two parts where reagents are mixed together, choosing from one type of aldehyde, one amine and one azide (from a possible family of two amines, two aldehydes and four azides) with different volumes, ratios, reaction times, and temperatures, whereby the reagents are passed through a copper coil reactor. Next, either cobalt or iron is added, again from a large number of possible quantities. The reactivity was determined by evaluating differences in pH, UV‐Vis, and mass spectra before and after the search was started. The algorithm was focused on the exploration of interesting regions, as defined by the outputs from the sensors, and this led to the discovery of a range of 1‐benzyl‐(1,2,3‐triazol‐4‐yl)‐N‐alkyl‐(2‐pyridinemethanimine) ligands and new complexes: [Fe(L¹)₂](ClO₄)₂ ( 1 ); [Fe(L²)₂](ClO₄)₂ ( 2 ); [Co₂(L³)₂](ClO₄)₄ ( 3 ); [Fe₂(L³)₂](ClO₄)₄ ( 4 ), which were crystallised and their structure confirmed by single‐crystal X‐ray diffraction determination, as well as a range of new supramolecular clusters discovered in solution using high‐resolution mass spectrometry.     

Engineering Iron–Nickel Nanoparticles for Magnetically Induced CO2 Methanation in Continuous Flow

Induction heating of magnetic nanoparticles (NPs) is a method to activate heterogeneous catalytic reactions. It requires nano‐objects displaying high heating power and excellent catalytic activity. Here, using a surface engineering approach, bimetallic NPs are used for magnetically induced CO₂ methanation, acting both as heating agent and catalyst. The organometallic synthesis of Fe₃₀Ni₇₀ NPs displaying high heating powers at low magnetic field amplitudes is described. The NPs are active but only slightly selective for CH₄ after deposition on SiRAlOx owing to an iron‐rich shell (25 mL min^?1, 25 mT, 300 kHz, conversion 71 %, methane selectivity 65 %). Proper surface engineering consisting of depositing a thin Ni layer leads to Fe₃₀Ni₇₀@Ni NPs displaying a very high activity for CO₂ hydrogenation and a full selectivity. A quantitative yield in methane is obtained at low magnetic field and mild conditions (25 mL min^?1, 19 mT, 300 kHz, conversion 100 %, methane selectivity 100 %).     

Metabolite profiling and in-vitro colon cancer protective activity of Cycas revoluta cone extract

Abstract

The methanolic extract of Cycas revoluta cone (MECR) was analyzed by GC-MS and UHPLC for metabolite profiling and was evaluated for anti-colon cancer property by using in vitro assays like Cell Viability Assay, Colony Formation Assay, ROS Determination, Flowcytometry, DAPI staining assay, Tunel assay. GC-MS and HPLC analysis confirmed the presence of different phytochemicals in the extract of Cycas revoluta cone. In-vitro studies showed MECR extract showed significant anti-colon cancer activity by reducing proliferation and inducing apoptosis in colon cancer cell (HCT-8) line, but no such activity was seen in normal colon cell (CCD-18Co) line. The investigation confirms that MECR may be a promising candidate in colon cancer protection.     

Fluorinated Alcohols: Magic Reaction Medium and Promoters for Organic Synthesis

Fluorinated alcohols have been widely used in the synthetic organic chemistry over the past decades. The unique properties such as the strong hydrogen‐bonding donor ability and low nucleophilicity allow them to promote organic reactions in the absence of any catalyst. These approaches have distinct advantages in terms of operational simplicity, practicability and environmental friendliness. Reactions promoted by fluorinated alcohols, including nucleophilic substitution reactions, annulation reactions, electrophilic reactions, dearomatization reactions, functionalization of multiple bond, epoxidation reactions and miscellaneous reactions have been summarized in this account.     

Artificial Water Channels: Towards Biomimetic Membranes for Desalination

Natural Aquaporin (AQP) channels are efficient water translocating proteins, rejecting ions. Inspired by this masterpiece of nature, Artificial Water Channels (AWCs) with controlled functional structures, can be potentially used to mimic the AQPs to a certain extent, offering flexible avenues toward biomimetic membranes for water purification. The objective of this paper is to trace the historical development and significant advancements of current reported AWCs. Meanwhile, we attempt to reveal important structural insights and supramolecular self-assembly principles governing the selective water transport mechanisms, toward innovative AWC-based biomimetic membranes for desalination.     

Bistability and explosive transients in surface reactions: the role of fluctuations and spatial correlations

We study the dynamics of a class of catalytic surface reactions in which an adsorbed molecule undergoes dissociation giving oxygen, which then rapidly reacts with H adatoms to give water. The reaction-diffusion equations predict bistability and explosive transients similar to those observed in several low-pressure experiments. Kinetic Monte Carlo simulations reveal however that the dynamics can be strongly affected by spontaneous, inhomogeneous fluctuations of composition on the surface. In particular, bifurcation points can be displaced and the explosive character of the transients can be lost, depending on a subtle balance between the rate of reaction and the mobility of the decomposing species. These effects can be quantified on the basis of a stochastic formulation of the dynamics taking into account spatial correlations. This approach allows to better delimit the applicability of the traditional reaction-diffusion modelling in the case of reactions such as the reduction of NO _x or SO _x species on catalytic surfaces.     

Performance studies of a full-length prototype for the CASTOR forward calorimeter at the CMS experiment

The Time-Of-Flight detector (TOF) of the ALICE experiment at the CERN LHC is based on Multi-gap Resistive Plate Chambers (MRPCs). The TOF detector consists of 152928 readout channels covering a total area of 141 m². In this paper the results of the calibration with cosmic-ray data collected during 2009 are presented.