Isolation of exosomes from whole blood by a new microfluidic device: proof of concept application in the diagnosis and monitoring of pancreatic cancer

Background: Exosomes are endocytic-extracellular vesicles with a diameter around 100 nm that play an essential role on the communication between cells. In fact, they have been proposed as candidates for the diagnosis and the monitoring of different pathologies (such as Parkinson, Alzheimer, diabetes, cardiac damage, infection diseases or cancer). Results: In this study, magnetic nanoparticles (Fe3O4NPs) were successfully functionalized with an exosome-binding antibody (anti-CD9) to mediate the magnetic capture in a microdevice. This was carried out under flow in a 1.6 mm (outer diameter) microchannel whose wall was in contact with a set of NdFeB permanent magnets, giving a high magnetic field across the channel diameter that allowed exosome separation with a high yield. To show the usefulness of the method, the direct capture of exosomes from whole blood of patients with pancreatic cancer (PC) was performed, as a proof of concept. The captured exosomes were then subjected to analysis of CA19-9, a protein often used to monitor PC patients. Conclusions: Here, we describe a new microfluidic device and the procedure for the isolation of exosomes from whole blood, without any need of previous isolation steps, thereby facilitating translation to the clinic. The results show that, for the cases analyzed, the evaluation of CA19-9 in exosomes was highly sensitive, compared to serum samples

Synergistic assembly of gold and copper-iron oxide nanocatalysts to promote the simultaneous depletion of glucose and glutathione

Glucose and glutathione (GSH) are key biomolecules for the regulation and growth of tumor cells. The use of inorganic nanocatalysts in biomedicine to target and deplete such specific molecules represents a novel and promising strategy against cancer. In this work, we present a ternary assembled nanohybrid based on Au and CuFe2O4 with the capability to simultaneously deplete glucose and GSH and generate reactive oxidative species (ROS) in a cascade process. We describe an example of a synergistic heterogeneous nanoarchitecture able to maintain the glucose oxidase-like activity of Au while preventing its deactivation in the presence of GSH. Au sites remain active due to the rapid response of the Cu–Fe co-catalyst to deplete GSH levels. This example of hybrid heterostructure represents an appealing alternative with dual-activity within the tumor microenvironment (TME) for potential anticancer therapy

Nitrogen-doped carbon nanodots deposited on titania nanoparticles: unconventional near-infrared active photocatalysts for cancer therapy

Cancer represents a major public health issue and a primary cause of death for the mankind and the search for alternative cancer treatments that assist or alleviate the drawbacks of current cancer therapies remains imperative. Nanocatalytic medicine represents a new discipline that aims at exploiting the unique response of heterogeneous catalysts exposed to unconventional conditions such as those encountered in the tumor microenvironment (TME). Photo-triggered cancer therapies using light-activable catalytic materiales can stimulate and activate multiple biological processes and represent a very promising field of study. Herein, we evaluate the use of carbon nanodots with different composition (CNDs) retrieved by laser pyrolysis as potential near-infrared (NIR) photosensitizers able to activate P25 semiconductor nanostructured photocatalysts. We describe the enhanced photocatalytic response towards glucose conversion and reactive oxygen species (ROS) generation upon irradiation with NIR-LEDs when CNDs doped with heteroatoms were tested. The most active photocatalysts were evaluated in the presence of cancer cells and revealed a promising photodynamic effect under NIR irradiation. This work represents one of the scarce examples of a conventional inorganic photocatalyst containing TiO2 that is translated into a biomedical application with a successful outcome

The Origin of The Acheulean: The 1.7 Million-Year-Old Site of FLK West, Olduvai Gorge (Tanzania)

The appearance of the acheulean is one of the hallmarks of human evolution. It represents the emergence of a complex behavior, expressed in the recurrent manufacture of large-sized tools, with standardized forms, implying more advance forethought and planning by hominins than those required by the precedent Oldowan technology. The earliest known evidence of this technology dates back to c. 1.7 Ma. and is limited to two sites (Kokiselei [Kenya] and Konso [Ethiopia]), both of which lack functionally-associated fauna. The functionality of these earliest Acheulean assemblages remains unknown. Here we present the discovery of another early Acheulean site also dating to c. 1.7 Ma from Olduvai Gorge. This site provides evidence of the earliest steps in developing the Acheulean technology and is the oldest acheulean site in which stone tools occur spatially and functionally associated with the exploitation of fauna. Simple and elaborate large-cutting tools (LCT) and bifacial handaxes co-exist at FLK West, showing that complex cognition was present from the earliest stages of the acheulean. Here we provide a detailed technological study and evidence of the use of these tools on the butchery and consumption of fauna, probably by early Homo erectus sensu lato

FLK West (Lower Bed II, Olduvai Gorge, Tanzania): a new early Acheulean site with evidence for human exploitation of fauna

This paper presents a detailed taphonomic study of the faunal assemblage from FLK West (Olduvai Gorge, Tanzania), a site with an Acheulean component that dates to 1.7 Ma. The faunal sample analysed here is distributed in different archaeological levels and is associated with a significant lithic accumulation including several large format tools and handaxes. The fauna indicates the proliferation of open environments similar to those found in other Bed II and late Bed I sites. Evidence of anthropogenic activity (e.g. defleshing activities and marrow consumption) has been identified in the form of cut and percussion marks. A photogrammetric and morphometric analysis suggests that these marks were produced with quartzite flakes and not with handaxes. Evidence of interaction with carnivores was also noted; tooth marks were observed on some bones. Such interaction indicates the existence of competition between humans and carnivores for the same ecological niche, and might lead us to reflect on the survival strategies of Lower Pleistocene hominins

The CARMENES search for exoplanets around M dwarfs

Context. The CARMENES instrument, installed at the 3.5 m telescope of the Calar Alto Observatory in Almería, Spain, was conceived to deliver high-accuracy radial velocity (RV) measurements with long-term stability to search for temperate rocky planets around a sample of nearby cool stars. Moreover, the broad wavelength coverage was designed to provide a range of stellar activity indicators to assess the nature of potential RV signals and to provide valuable spectral information to help characterise the stellar targets. Aims: We describe the CARMENES guaranteed time observations (GTO), spanning from 2016 to 2020, during which 19 633 spectra for a sample of 362 targets were collected. We present the CARMENES Data Release 1 (DR1), which makes public all observations obtained during the GTO of the CARMENES survey. Methods: The CARMENES survey target selection was aimed at minimising biases, and about 70% of all known M dwarfs within 10 pc and accessible from Calar Alto were included. The data were pipeline-processed, and high-level data products, including 18 642 precise RVs for 345 targets, were derived. Time series data of spectroscopic activity indicators were also obtained. Results: We discuss the characteristics of the CARMENES data, the statistical properties of the stellar sample, and the spectroscopic measurements. We show examples of the use of CARMENES data and provide a contextual view of the exoplanet population revealed by the survey, including 33 new planets, 17 re-analysed planets, and 26 confirmed planets from transiting candidate follow-up. A subsample of 238 targets was used to derive updated planet occurrence rates, yielding an overall average of 1.44 ± 0.20 planets with 1 M⊕ < Mpl sin i < 1000 M⊕ and 1 day < Porb < 1000 days per star, and indicating that nearly every M dwarf hosts at least one planet. All the DR1 raw data, pipeline-processed data, and high-level data products are publicly available online. Conclusions: CARMENES data have proven very useful for identifying and measuring planetary companions. They are also suitable for a variety of additional applications, such as the determination of stellar fundamental and atmospheric properties, the characterisation of stellar activity, and the study of exoplanet atmospheres

Incidence, clinical characteristics and management of inflammatory bowel disease in Spain: large-scale epidemiological study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD—Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)—during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100, 000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31–56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Data Descriptor : A European Multi Lake Survey dataset of environmental variables, phytoplankton pigments and cyanotoxins

Under ongoing climate change and increasing anthropogenic activity, which continuously challenge ecosystem resilience, an in-depth understanding of ecological processes is urgently needed. Lakes, as providers of numerous ecosystem services, face multiple stressors that threaten their functioning. Harmful cyanobacterial blooms are a persistent problem resulting from nutrient pollution and climate-change induced stressors, like poor transparency, increased water temperature and enhanced stratification. Consistency in data collection and analysis methods is necessary to achieve fully comparable datasets and for statistical validity, avoiding issues linked to disparate data sources. The European Multi Lake Survey (EMLS) in summer 2015 was an initiative among scientists from 27 countries to collect and analyse lake physical, chemical and biological variables in a fully standardized manner. This database includes in-situ lake variables along with nutrient, pigment and cyanotoxin data of 369 lakes in Europe, which were centrally analysed in dedicated laboratories. Publishing the EMLS methods and dataset might inspire similar initiatives to study across large geographic areas that will contribute to better understanding lake responses in a changing environment.Peer reviewe