The determination of the addition variation and geometrical isomerism of a polybutadiene as a function of molecular weight by preparative gel permeation chromatography and infrared analysis

The addition variation, 1,2 and 1,4 units, and the geometrical isomerism, 1,4-cis and 1,4-trans units, of a fractionated polybutadiene were determined as a function of molecular weight using preparative gel permeation chromatography followed by infrared analysis of the fractions. Both the addition variation and geometrical isomerism remained essentially constant across the molecular weight distribution.     

Design,Synthesis, and Biological Evaluation of Coumarin Derivatives Tethered to an Edrophonium‐like Fragment as Highly Potent and Selective Dual Binding Site Acetylcholinesterase Inhibitors

A large series of substituted coumarins linked through an appropriate spacer to 3‐hydroxy‐N,N‐dimethylanilino or 3‐hydroxy‐N,N,N‐trialkylbenzaminium moieties were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The highest AChE inhibitory potency in the 3‐hydroxy‐N,N‐dimethylanilino series was observed with a 6,7‐dimethoxy‐3‐substituted coumarin derivative, which, along with an outstanding affinity (IC₅₀=0.236 nM ) exhibits excellent AChE/BChE selectivity (SI>300 000). Most of the synthesized 3‐hydroxy‐N,N,N‐trialkylbenzaminium salts display an AChE affinity in the sub‐nanomolar to picomolar range along with excellent AChE/BChE selectivities (SI values up to 138 333). The combined use of docking and molecular dynamics simulations permitted us to shed light on the observed structure–affinity and structure–selectivity relationships, to detect two possible alternative binding modes, and to assess the critical role of π–π stacking interactions in the AChE peripheral binding site.     

萃取剂对泥炭腐植酸性质和微量元素的影响

氢氧化钠（NaOH）和焦磷酸钠（Na4P2O7）是从陆相环境中分离腐植酸（HA）最常用的2种萃取剂。为了评价萃取剂对HA性质和微量元素的影响,采用3种不同溶液,即（a）0.5moi／L NaOH;（b）01mol／LNa4P2O7;（c）0．5mol／LNaOH＋0.1mol／LNa。巳0。从54-泥炭藓泥炭样品中分离HA,并分析了萃取得到的HA的灰分含量、元素组成和主要原子比,以及傅立叶变换红外光谱（FT-IR）和发光光谱特征。此外,还用X射线荧光法测定泥炭样品和HA中的Br、Cu、Fe、Ni、Pb和Zn的含量。试验结果表明：用NaOH和NaOH＋Na4P2O7萃取的HA在灰分、元素含量和光谱特征上十分相似,而Na4P2O7溶液通常降低了萃取率,似乎是影响了HA的本质,使之具有更加复合和芳香性的特征。与原泥炭样品比较,不论什么萃取剂萃取得到的HA,其Br、Cu和Ni含量均增加,而Fe、Pb和Zn含量减少。相比于其他的方法,用Na4P2O2萃取得到的HA含有更多Br、Cu、Ni和Zn,可能是因为HA的芳香性分子对这些元素显示出更大的亲和力。     

Prognostic and Theranostic Applications of Positron Emission Tomography for a Personalized Approach to Metastatic Castration-Resistant Prostate Cancer

Metastatic castration-resistant prostate cancer (mCRPC) represents a condition of progressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of manifestations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been profoundly modified by introducing novel therapeutic tools such as antiandrogen drugs (i.e., abiraterone acetate and enzalutamide), immunotherapy through sipuleucel-T, and targeted alpha therapy (TAT). This variety of approaches calls for unmet need of biomarkers suitable for patients’ pre-treatment selection and prognostic stratification. In this scenario, imaging with positron emission computed tomography (PET/CT) presents great and still unexplored potential to detect specific molecular and metabolic signatures, some of whom, such as the prostate specific membrane antigen (PSMA), can also be exploited as therapeutic targets, thus combining diagnosis and therapy in the so-called “theranostic” approach. In this review, we performed a web-based and desktop literature research to investigate the prognostic and theranostic potential of several PET imaging probes, such as ¹⁸F-FDG, ¹⁸F-choline and ⁶⁸Ga-PSMA-11, also covering the emerging tracers still in a pre-clinical phase (e.g., PARP-inhibitors’ analogs and the radioligands binding to gastrin releasing peptide receptors/GRPR), highlighting their potential for defining personalized care pathways in mCRPC.     

The Paradox Effect of Calcification in Carotid Atherosclerosis: Microcalcification Is Correlated with Plaque Instability

Background: this study aims to investigate the possible association among the histopathologic features of carotid plaque instability, the presence of micro- or macrocalcifications, the expression of in situ inflammatory biomarkers, and the occurrence of the major risk factors in this process in a large series of carotid plaques. Methods: a total of 687 carotid plaques from symptomatic and asymptomatic patients were collected. Histological evaluation was performed to classify the calcium deposits in micro or macrocalcifications according to their morphological features (location and size). Immunohistochemistry was performed to study the expression of the main inflammatory biomarkers. Results: results here reported demonstrated that calcifications are very frequent in carotid plaques, with a significant difference between the presence of micro- and macrocalcifications. Specifically, microcalcifications were significantly associated to high inflamed unstable plaques. Paradoxically, macrocalcifications seem to stabilize the plaque and are associated to a M2 macrophage polarization instead. Discussion: the characterization of mechanisms involved in the formation of carotid calcifications can lay the foundation for developing new strategies for the management of patients affected by carotid atherosclerosis. Data of this study could provide key elements for an exhaustive evaluation of carotid plaque calcifications allowing to establish the risk of associated clinical events.     

Dextran-Curcumin Nanosystems Inhibit Cell Growth and Migration Regulating the Epithelial to Mesenchymal Transition in Prostate Cancer Cells

Functional nanocarriers which are able to simultaneously vectorize drugs to the site of interest and exert their own cytotoxic activity represent a significant breakthrough in the search for effective anticancer strategies with fewer side effects than conventional chemotherapeutics. Here, we propose previously developed, self-assembling dextran-curcumin nanoparticles for the treatment of prostate cancer in combination therapy with Doxorubicin (DOXO). Biological effectiveness was investigated by evaluating the cell viability in either cancer and normal cells, reactive oxygen species (ROS) production, apoptotic effect, interference with the cell cycle, and the ability to inhibit cell migration and reverse the epithelial to mesenchymal transition (EMT). The results proved a significant enhancement of curcumin efficiency upon immobilization in nanoparticles: IC₅₀ reduced by a half, induction of apoptotic effect, and improved ROS production (from 67 to 134%) at low concentrations. Nanoparticles guaranteed a pH-dependent DOXO release, with a more efficient release in acidic environments. Finally, a synergistic effect between nanoparticles and Doxorubicin was demonstrated, with the free curcumin showing additive activity. Although in vivo studies are required to support the findings of this study, these preliminary in vitro data can be considered a proof of principle for the design of an effective therapy for prostate cancer treatment.     

Some problems related to an environmental factual database: the case Aeolian project

Factual databanks can make an important contribution to environmental management. They help considerably with the difficult processes of integrating the various scientific languages used, and also with the development of valid methods for interdisciplinary research. In the planning the Aeolian project (a multidisciplinary study of an Archipelago north of Sicily), it was considered useful to include a group of workers on methodology and computer science. The hope is that they will help to facilitate the exchange of data and thus contribute to a better understanding of the various phenomena occurring on the islands. This paper discusses the conceptual working aspects of environmental information, together with those characteristics that render it suitable for inclusion in a modern computer‐based system.     

Measurement of number-average molecular weights and second viral coefficients of polyolefins using an improved vapor pressure osmometer

Operation of an improved design of a vapor pressure osmometer for polyolefins at 140°C is described. Reproducibility of ±10% of the measured number-average molecular weight (M _n) was obtained with a maximum M _n of about 45,000–50,000. Results are reported for some standard and commercial, linear and branched polyethylenes and for commercial polypropylenes.