The Potentiality of Plant-Derived Nanovesicles in Human Health—A Comparison with Human Exosomes and Artificial Nanoparticles

Research in science and medicine is witnessing a massive increases in literature concerning extracellular vesicles (EVs). From a morphological point of view, EVs include extracellular vesicles of a micro and nano sizes. However, this simplistic classification does not consider both the source of EVs, including the cells and the species from which Evs are obtained, and the microenvironmental condition during EV production. These two factors are of crucial importance for the potential use of Evs as therapeutic agents. In fact, the choice of the most suitable Evs for drug delivery remains an open debate, inasmuch as the use of Evs of human origin may have at least two major problems: (i) autologous Evs from a patient may deliver dangerous molecules; and (ii) the production of EVs is also limited to cell factory conditions for large-scale industrial use. Recent literature, while limited to only a few papers, when compared to the papers on the use of human EVs, suggests that plant-derived nanovesicles (PDNV) may represent a valuable tool for extensive use in health care.     

Alternative PWHT to Improve High-Temperature Mechanical Properties of Advanced 9Cr Steel Welds

Creep-resistant 9Cr steels are extremely important in thermal power generation industry due to their marked resistance to creep and corrosion. The weldability of these alloys is critical since they are used in welded construction equipment. The required mechanical properties are achieved after post-weld heat treatment. This study examined the effect of different post-weld heat treatments on microstructure and mechanical properties of creep strength-enhanced 9Cr steel welding deposits. It was obtained with an experimental flux-cored arc welding wire used under protective gas (Ar-20% CO₂). The heat treatments used were: (1) tempering (760 °C?×?2 h), (2) solubilizing (1050 °C?×?1 h)?+?tempering (760 °C?×?2 h) and (3) solubilizing (1150 °C?×?1 h)?+?first tempering (660 °C?×?3 h)?+?second tempering (660 °C?×?3 h). All-weld metal chemical composition was analyzed, and hot tensile tests were carried out at different temperatures. Charpy-V impact tests and Vickers microhardness measurements were also performed. Microstructures were studied using x-ray diffraction and optical and scanning electron microscopy. In all cases, a martensitic matrix with intergranular and intra-granular precipitates was detected. In the as-welded condition, δ-ferrite was also found. Microhardness dropped, and the impact energy increased with post-weld heat treatments. The highest hot tensile strength result was achieved with samples submitted to austenization at 1150 °C and double tempering at 660 °C.     

Effect of post-weld heat treatment on the wear resistance of hardfacing martensitic steel deposits

The effect of different post-weld heat treatments on the microstructure and wear resistance of martensitic deposits were studied. The deposit was welded using a metal-cored tubular wire, in the flat welding position, on a 375 × 75 × 19 mm SAE 1010 plate, using 98% Ar–2% CO₂ shielding gas mixture and with an average heat input of 2.8 kJ/mm. The samples were heat treated at temperatures between 500 and 680°C for 2 h. Chemical composition, Vicker's microhardness and wear properties with AMSLER tests in a sliding condition were determined. In the as welded condition, the microstructure was principally composed of martensite and retained austenite. Significant variations in wear resistance and hardness were measured for different tempering temperatures. For the different heat-treated conditions, it was observed that the decomposition of retained austenite to martensite and carbide precipitation was associated with the tempering of martensite. A secondary hardness effect was detected with maximum hardness of 710 HV for 550°C heat treatment temperature. The best performance in wear test was obtained for this condition. Wear rates for the different conditions were obtained and mathematical expressions were developed. For each case, wear mechanisms were analyzed.     

Effect of welding procedure on wear behaviour of a modified martensitic tool steel hardfacing deposit

In the last years hardfacing became an issue of intense development related to wear resistant applications. Welding deposits can functionalize surfaces and reclaim components extending their service life. Tool steels are widely used in hardfacing deposits to provide improved wear properties. Nevertheless systematic studies of wear behaviour of new alloys deposited by hardfacing, under different service conditions are scarce. In this work the effects of shielding gas, heat input and post-weld heat treatment on the microstructural evolution and wear resistance of a modified AISI H13 martensitic tool steel deposited by semi-automatic gas shielded arc welding process using a tubular metal-cored wire, were studied. Four coupons were welded with different welding parameters. The shielding gases used were Ar–2% CO₂ and Ar–20% CO₂ mixtures and two levels of heat input were selected: 2 and 3 kJ/mm. The as welded and 550 °C–2 h post-weld heat treated conditions were considered. From these coupons, samples were extracted for testing metal–metal wear under condition of pure sliding with a load of 500 N. Chemical compositions were determined; microstructure and microhardness were assessed. It was found that content of retained austenite in the microstructure varied with the welding condition and that heat-treated samples showed secondary hardening, associated with precipitation phenomena. Nevertheless, as welded samples showed higher wear resistance than heat treated specimens. Under these test conditions post-weld heat treatment led to a reduction in wear resistance. The best wear behaviour was observed in samples welded with low heat input and under the lowest oxygen potential shielding gas used here, in the as welded condition. The intervening mechanism was mild oxidative. These results were explained in terms of the relative oxidation resistance stemming from different welding conditions.     

Effect of welding parameters on microstructure of Fe-based nanostructured weld overlay deposited through FCAW-S

Lately, modern hardfacing tubular wires for semiautomatic welding with gas protection and without it have been developed. These wires deposit Fe-based nanostructured alloys with high abrasive wear resistance. The information on these new consumables is scarce, especially about the effect that the welding parameters (heat input, shielding gas, arc voltage, current intensity, etc.) have on the deposit, its microstructure and, consequently, its wear behaviour. For this reason, in this article, we study the effect of heat input (voltage, intensity of current and welding velocity) on the properties of a flux-cored arc welding Fe-based nanostructured deposit obtained without gas protection. This study is a continuation of a previous one in which the same consumable was used under shielding gas. Bead on plate samples were welded using heat inputs between 0.5 and 3.5 k/mm. The dimensional study was performed on the beads, chemical composition was determined and the microstructure was analysed using optical and electronic microscopy and X-ray diffraction. Microhardness, crystallite size and dilution percentage were also measured. An important influence of the welding parameters on the bead geometry and the microstructure was observed. The operational behaviour of this wire, welded without shielding gas, was very good.     

Biomarkers in Prostate Cancer Diagnosis: From Current Knowledge to the Role of Metabolomics and Exosomes

Early detection of prostate cancer (PC) is largely carried out using assessment of prostate-specific antigen (PSA) level; yet it cannot reliably discriminate between benign pathologies and clinically significant forms of PC. To overcome the current limitations of PSA, new urinary and serum biomarkers have been developed in recent years. Although several biomarkers have been explored in various scenarios and patient settings, to date, specific guidelines with a high level of evidence on the use of these markers are lacking. Recent advances in metabolomic, genomics, and proteomics have made new potential biomarkers available. A number of studies focused on the characterization of the specific PC metabolic phenotype using different experimental approaches has been recently reported; yet, to date, research on metabolomic application for PC has focused on a small group of metabolites that have been known to be related to the prostate gland. Exosomes are extracellular vesicles that are secreted from all mammalian cells and virtually detected in all bio-fluids, thus allowing their use as tumor biomarkers. Thanks to a general improvement of the technical equipment to analyze exosomes, we are able to obtain reliable quantitative and qualitative information useful for clinical application. Although some pilot clinical investigations have proposed potential PC biomarkers, data are still preliminary and non-conclusive.     

Evaluation of the Molecular Landscape in PD-L1 Positive Metastatic NSCLC: Data from Campania,Italy

Background: Immune-checkpoint inhibitors (ICIs) have increased and improved the treatment options for patients with non-oncogene-addicted advanced stage non-small cell lung cancer (NSCLC). However, the role of ICIs in oncogene-addicted advanced stage NSCLC patients is still debated. In this study, in an attempt to fill in the informational gap on the effect of ICIs on other driver mutations, we set out to provide a molecular landscape of clinically relevant oncogenic drivers in programmed death-ligand 1 (PD-L1) positive NSCLC patients. Methods: We retrospectively reviewed data on 167 advanced stage NSCLC PD-L1 positive patients (≥1%) who were referred to our clinic for molecular evaluation of five driver oncogenes, namely, EGFR, KRAS, BRAF, ALK and ROS1. Results: Interestingly, n = 93 (55.7%) patients showed at least one genomic alteration within the tested genes. Furthermore, analyzing a subset of patients with PD-L1 tumor proportion score (TPS) ≥ 50% and concomitant gene alterations (n = 8), we found that n = 3 (37.5%) of these patients feature clinical benefit with ICIs administration, despite the presence of a concomitant KRAS gene alteration. Conclusions: In this study, we provide a molecular landscape of clinically relevant biomarkers in NSCLC PD-L1 positive patients, along with data evidencing the clinical benefit of ICIs in patient NSCLC PD-L1 positive alterations.     

Estimation of geomorphically significant flows in alpine streams of the Rocky Mountains,Colorado (USA)

Streamflows recorded at 24 gauging stations in the Rocky Mountains of Colorado were analyzed to derive regional regression equations for estimating the natural flow duration and flood frequency in reaches where the natural flows are unknown or have been altered by diversion or regulation. The principal objective of this analysis is to determine whether the relatively high, infrequent, but geomorphically and ecologically important flows in the Rocky Mountains can be accurately estimated by regional flow duration equations. The region considered in this study is an area of relatively abundant runoff, and, consequently, intense water resources development. The specific streams analyzed here, however, are unaltered and remain nearly pristine. Regional flow duration equations are derived for two situations. When the mean annual discharge is known, flows ≧10% of the time can be estimated with an uncertainty of ±9% for the 10% exceedance flow, to ±11% for the 1.0% exceedance flow. When the mean annual discharge is unknown, the relatively high, infrequent flow can be estimated using the mean basin precipitation rate (in m³/s), and basin relief with an uncertainty of ±23% for the 10% exceedance flow to ±21% for the 1.0% exeedance flow. The uncertainty in estimated discharges using the equations derived in this analysis is substantially smaller than has been previously reported, especially for the geomorphically significant flows which are relatively large and infrequent. The improvement is due primarily to the quality of streamflow records analyzed and a well‐defined hydrologic region.     

Island dynamics in a braided river from analysis of historical maps and air photographs

An analysis of island and active corridor dynamics is presented for a 16 km island‐braided reach of the gravel‐bed Tagliamento River (Italy) based upon information extracted, geocorrected and registered to a common base from three map (1803, 1833, 1927) and nine aerial photograph sources (1944/6, 1954, 1970, 1986, 1991, 1996, 1997, 1999, 2005). The active corridor width showed a general decline over the study period but with some recent widening. Adjustments in active corridor width were achieved through processes of floodplain avulsion, island attachment and progressive encroachment of the edge of the active corridor across gravel areas. These adjustments were accompanied by the preferential creation of dissection (floodplain avulsion) islands during periods of widening and the construction of mid islands within the corridor during periods of narrowing. Changes in island extent were achieved by rapid island turnover, which reached a maximum rate of over 50% per annum when corridor narrowing was most rapid between 1970 and 1991. Very few island surfaces were found to persist for more than 24 years. Despite this enormous dynamism and apparent cyclic behaviour, between 1944/6 and 2005 the ratio of island area to active corridor area remained relatively constant at around 0.08 and supported a consistently high bankfull shoreline to downstream length ratio of around 6 km · km^?1. These intrinsic properties of the dynamics of the study reach and other island‐braided channels need to be recognized and maintained by river managers because they represent a characteristic habitat dynamism that is crucial to the maintenance of ecological integrity. Copyright © 2008 John Wiley & Sons, Ltd.