Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients

The purpose of this study was to evaluate the association between four distinct histopathological features: (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, plus (4) tumor budding and two gene expression-based classifiers—(1) consensus molecular subtypes (CMS) plus (2) colorectal cancer intrinsic subtypes (CRIS). All four histopathological features were retrospectively scored on hematoxylin and eosin sections of the most invasive part of the primary tumor in 218 stage II and III colon cancer patients from two independent cohorts (AMC-AJCC-90 and AC-ICAM). RNA-based CMS and CRIS assignments were independently obtained for all patients. Contingency tables were constructed and a χ2 test was used to test for statistical significance. Odds ratios with 95% confidence intervals were calculated. The presence of tumor infiltrating lymphocytes and a mucinous phenotype (>50% mucinous surface area) were strongly correlated with CMS1 (p < 0.001 and p = 0.008) and CRIS-A (p = 0.006 and p < 0.001). The presence of mucus (≥ 10%) was associated with CMS3: mucus was present in 64.1% of all CMS3 tumors (p < 0.001). Although a clear association between tumor-stroma ratio and CMS4 was established in this study (p = 0.006), still 32 out of 61 (52.5%) CMS4 tumors were scored as stroma-low, indicating that CMS4 tumors cannot be identified solely based on stromal content. Higher budding counts were seen in CMS4 and CRIS-B tumors (p = 0.045 and p = 0.046). No other associations of the measured parameters were seen for any of the other CRIS subtypes. Our analysis revealed clear associations between histopathologic features and CMS or CRIS subtypes. However, identification of distinct molecular subtypes solely based on histopathology proved to be infeasible. Combining both molecular and morphologic features could potentially improve patient stratification.     

Preliminary Investigation on the Involvement of Cytoskeleton-Related Proteins,DAAM1 and PREP,in Human Testicular Disorders

Herein, for the first time, the potential relationships between the cytoskeleton-associated proteins DAAM1 and PREP with different testicular disorders, such as classic seminoma (CS), Leydig cell tumor (LCT), and Sertoli cell-only syndrome (SOS), were evaluated. Six CS, two LCT, and two SOS tissue samples were obtained during inguinal exploration in patients with a suspect testis tumor based on clinical examination and ultrasonography. DAAM1 and PREP protein levels and immunofluorescent localization were analyzed. An increased DAAM1 protein level in CS and SOS as compared to non-pathological (NP) tissue was observed, while LCT showed no significant differences. Conversely, PREP protein level increased in LCT, while it decreased in CS and SOS compared to NP tissue. These results were strongly supported by the immunofluorescence staining, revealing an altered localization and signal intensity of DAAM1 and PREP in the analyzed samples, highlighting a perturbed cytoarchitecture. Interestingly, in LCT spermatogonia, a specific DAAM1 nuclear localization was found, probably due to an enhanced testosterone production, as confirmed by the increased protein levels of steroidogenic enzymes. Finally, although further studies are needed to verify the involvement of other formins and microtubule-associated proteins, this report raised the opportunity to indicate DAAM1 and PREP as new potential markers, supporting the cytoskeleton dynamics changes occurring during normal and/or pathological cell differentiation.     

Zeolites in biomedical application: Zn-exchanged clinoptilolite-rich rock as active carrier for antibiotics in anti-acne topical therapy

A clinoptilolite-rich rock was evaluated as inorganic Zn²⁺ releasing carrier for antibiotic erythromycin. The perspective is its use in the topical treatment of acne, a diffused skin pathology, given the efficacy of zinc-erythromycin combination against resistant Propionibacterium strains. The tested rock is an ash-rich epiclastite collected in Northern–Central part of Sardinia island (Italy). ICP chemical analyses of the bulk rock evidenced a composition compatible with topical applications. A 66 wt.% of clinoptilolite content was determined by means of XRD analysis (reference intensity ratio [RIR] technique). EDS chemical analyses of zeolite crystals were performed on polished thin section. The CEC of the rock is 1.45±0.08 meq/g. Using a specific exchange method, the material was previously Na-conditioned then Zn-conditioned. A substantially complete Zn-form was obtained, as demonstrated by AAS analyses. A back-exchange reaction toward Na-form was performed in the same conditions (65 °C in 1 M NaCl solution): zinc release was fast and almost complete (94%). Zn-conditioned powder was then micronized to achieve a volume/surface ratio suitable for a topical therapy. After micronization, the specific surface area, determined by BET gas adsorption, was 30.2 m²/g, and 92% of the powdered rock was lower than 30 μm in size (measured by a Coulter Counter apparatus); the so-called “volume-surface diameter” was 6.48 μm, compatible with the intended topical application. Zn²⁺ release was measured on micronized rock at 37 °C both in physiologic solution as in 0.05 M KH₂PO₄/Na₂HPO₄ buffer. Also in these conditions, a prompt and significant zinc release was recorded: after 30 min, 68% and 60%, respectively. Erythromycin was charged onto the micronized material using a solvent evaporation method. HPLC determinations showed that 85% of the drug contacted with the carrier was loaded. The simultaneous release of zinc and erythromycin were evaluated in phosphate buffer. Eighty-two percent of the loaded antibiotic was released after 30 min. Zinc exchange is substantially unaffected by the contemporary drug release. The request to file an international patent for this pharmaceutical application has been accepted by the European International Preliminary Examination Office.     

Redispersible Polymer Powders with High Bio-Based Content from Core–Shell Nanoparticles

Redispersible polymer powders (RDPPs), i.e., additives obtained from core–shell nanoparticles and commercialized in the form of a dry powder, find intensive application in the concrete industry. However, they are mainly produced from fossil resources. Therefore, the development of bio-based RDPPs is important to reduce the carbon footprint of these additives. In this work, two types of core–shell nanoparticles with a high percentage of bio-based content are synthesized and show to be good candidates as RDPPs. In the first case, up to 75% of bio-based content is obtained by combining lauryl acrylate, derived from coconut and palm kernel oil, as main core material, with isobornyl methacrylate, coming from pine resin, exploited to create the outer harder shell. In the second case, a degradable macromonomer obtained by the ring opening polymerization of lactide using 2-hydroxyethyl methacrylate as initiator is used as the core-forming monomer to obtain degradable RDPPs. In both cases, the particles are synthesized with a two-step emulsion polymerization process conducted in one pot and then spray-dried to obtain the RDPPs of interest. The morphology and redispersibility of the powders are characterized. Finally, their use as concrete additives is preliminarily assessed by evaluating their effect on changes in the surface morphologies of concrete specimens.     

Catalysis of Transesterification Reactions by a Self-Assembled Nanosystem

Histidine-containing peptides self-assemble on the surface of monolayer protected gold nanoparticles to form a catalytic system for transesterification reactions. Self-assembly is a prerequisite for catalysis, since the isolated peptides do not display catalytic activity by themselves. A series of catalytic peptides and substrates are studied in order to understand the structural parameters that are of relevance to the catalytic efficiency of the system. It is shown that the distance between the His-residue and the anionic tail does not affect the catalytic activity. On the other hand, the catalytic His-residue is sensitive to the chemical nature of the flanking amino acid residues. In particular, the presence of polar Ser-residues causes a significant increase in activity. Finally, kinetic studies of a series of substrates reveal that substrates with a hydrophobic component are very suitable for this catalytic system.     

Pressurised flash drying of Yallourn lignite

A previously developed 1D model of lignite drying for pulverised lignite feeding into a conventional pulverised fuel boiler during the coal milling process is applied to lignite in an entrained flow configuration at elevated pressure. A combustor fired with diesel and air was used to produce a flue gas at 800 °C and 10 atm to flash dry Yallourn lignite at a nominal feed rate of 725 kg/h along a 50 m duct. A coal feeder arrangement was also developed which provides a simple positive feeding device for feeding against a back pressure. The feeder takes as an input coal which is nominally <50 mm and discharges it as a finely divided product with a mean particle size of approximately 1.0-1.5 mm. The comparison between model predictions and measured temperature profiles for the flue gas and final moisture content of the dried coal product showed excellent agreement. Coal moisture was reduced from 67 wt% to between 30 and 40 wt%, depending upon on the coal feed rate and particle size. The small variation in the final outlet temperature observed between the model and experimental results is due to heat losses from the exposed duct work to the environment.     

Flow Metal‐Free Ar?C Bond Formation via Photogenerated Phenyl Cations

A convenient photochemical flow protocol for the formation of aryl‐carbon bonds via photogenerated phenyl cations has been developed. A wide range of phenylated products, including biaryls, allylarenes, 2‐arylacetals and benzyl γ‐lactones, was smoothly synthesized in satisfactory yields under metal‐free conditions. The adoption of a flow reactor often allowed us to adopt higher concentrations of substrates and shorter irradiation times compared to those usually employed in batch systems.

     

Deactivation of a Ni-Based Reforming Catalyst During the Upgrading of the Producer Gas, from Simulated to Real Conditions

The deactivation of a nickel reforming catalyst during the upgrading of the producer gas obtained by gasification of lignocellulosic biomass was studied. The research involved several steps: the selective deactivation of the catalyst in a laboratory scale; the streaming of the catalyst with the producer gas of a downdraft and an oxygen/steam circulating fluidized bed (CFB) gasifier; and tests in a reformer placed in a slipstream of the CFB gasifier. The information obtained allowed to elucidate the catalyst deactivation mechanisms taking place during the reforming of the producer gas: physical deactivation by deposition of fine ashes, aerosol particulate or carbon; poisoning by H₂S and HCl present in the gas phase and thermal sintering because of the high operation temperatures required to avoid the chemical deactivation. These physical and chemical effects depended on the composition of the biomass fuel.