Lack of Fibronectin Extra Domain A Alternative Splicing Exacerbates Endothelial Dysfunction in Diabetes

Glucose-induced changes of artery anatomy and function account for diabetic vascular complications, which heavily impact disease morbidity and mortality. Since fibronectin containing extra domain A (EDA\u2009+\u2009FN) is increased in diabetic vessels and participates to vascular remodeling, we wanted to elucidate whether and how EDA\u2009+\u2009FN is implicated in diabetes-induced endothelial dysfunction using isometric-tension recording in a murine model of diabetes. In thoracic aortas of EDA(-/-), EDA(+/+) (constitutively lacking and expressing EDA\u2009+\u2009FN respectively), and of wild-type mice (EDA(wt/wt)), streptozotocin (STZ)-induced diabetes impaired endothelial vasodilation to acetylcholine, irrespective of genotype. However STZ\u2009+\u2009EDA(-/-) mice exhibited increased endothelial dysfunction compared with STZ\u2009+\u2009EDA(+/+) and with STZ\u2009+\u2009EDA(wt/wt). Analysis of the underlying mechanisms revealed that STZ\u2009+\u2009EDA(-/-) mice show increased oxidative stress as demonstrated by enhanced aortic superoxide anion, nitrotyrosine levels and expression of NADPH oxidase NOX4 and TGF-\u3b21, the last two being reverted by treatment with the antioxidant n-acetylcysteine. In contrast, NOX1 expression and antioxidant potential were similar in aortas from the three genotypes. Interestingly, reduced eNOS expression in STZ\u2009+\u2009EDA(+/+) vessels is counteracted by increased eNOS coupling and function. Although EDA\u2009+\u2009FN participates to vascular remodelling, these findings show that it plays a crucial role in limiting diabetic endothelial dysfunction by preventing vascular oxidative stress

Engineered Sleeping Beauty Transposon as Efficient System to Optimize Chimp Adenoviral Production

Sleeping Beauty (SB) is the first DNA transposon employed for efficient transposition in vertebrate cells, opening new applications for genetic engineering and gene therapies. A transposon-based gene delivery system holds the favourable features of non-viral vectors and an attractive safety profile. Here, we employed SB to engineer HEK293 cells for optimizing the production of a chimpanzee Adenovector (chAd) belonging to the Human Mastadenovirus C species. To date, chAd vectors are employed in several clinical settings for infectious diseases, last but not least COVID-19. A robust, efficient and quick viral vector production could advance the clinical application of chAd vectors. To this aim, we firstly swapped the hAd5 E1 with chAd-C E1 gene by using the CRISPR/Cas9 system. We demonstrated that in the absence of human Ad5 E1, chimp Ad-C E1 gene did not support HEK293 survival. To improve chAd-C vector production, we engineered HEK293 cells to stably express the chAd-C precursor terminal protein (ch.pTP), which plays a crucial role in chimpanzee Adenoviral DNA replication. The results indicate that exogenous ch.pTP expression significantly ameliorate the packaging and amplification of recombinant chAd-C vectors thus, the engineered HEK293ch.pTP cells could represent a superior packaging cell line for the production of these vectors

Metformin and aspirin treatment could lead to an improved survival rate for Type 2 diabetic patients with stage II and III colorectal adenocarcinoma relative to non-diabetic patients

Metformin, the drug of choice in the treatment of type 2 diabetes mellitus (DM2), in addition to aspirin (ASA), the drug prescribed for cardioprotection of diabetic and non\u2010diabetic patients, have an inhibitory effect on cancer cell survival. The present population\u2010based study conducted in the province of Trieste (Italy), aimed to investigate the prevalence of DM2 in patients with colorectal adenocarcinoma (CRC) and survival for CRC in diabetic and nondiabetic patients. All permanent residents diagnosed with a CRC between 2004 and 2007 were ascertained through the regional health informa\u2010 tion system. CRC\u2010speci c and relative survival probabilities were computed for each group of patients de ned by CRC stage, presence or absence of DM2 treated with metformin, and presence or absence of daily ASA therapy. A total of 515 CRC patients without DM2 and 156 with DM2 treated with metformin were enrolled in the study. At the time of CRC diagnosis, 71 (14%) nondiabetic and 39 (25%) diabetic patients were taking ASA daily. The five\u2010year relative survival for stage III CRC was 101% [95% con dence interval (CI)=76\u2010126] in the 18 patients with DM2 treated with metformin and ASA, 55% (95% CI=31\u201078) in the 23 without DM2 treated with ASA, 55% (95% CI=45\u201065) in the 150 without DM2 not taking ASA, and 29% (95% CI=13\u201045) in the 43 with DM2 treated with metformin, however not with ASA. The ndings support the hypothesis of a possible inhibitory effect of metformin and ASA on CRC cells. Randomized controlled trials are required to verify this hypothesis

Improvement of pentathiophene/fullerene planar heterojunction organic photovoltaic cells through MoO3/CuI anode buffer bilayer

Organic photovoltaic cells (OPVCs) are based on a heterojunction electron donor (ED)/electron acceptor (EA). In the present work, the electron donor which is also the absorber of light is pentathiophene. The typical cells were ITO/ABL/Pentathiophene/fullerene /Alq3/Al with ABL = MoO3, CuI, MoO3/CuI. After optimisation of the pentathiophene thickness, 70 nm, the highest efficiency, 0.81%, is obtained with the bilayer MoO3/CuI as ABL. In order to understand these results the pentathiophene films deposited onto the different ABLs were characterized by scanning electron microscopy, atomic force microscopy, X-rays diffraction, optical absorption and electrical characterization. It is shown that CuI improves the conductivity of the pentathiophene layer through the modification of the film structure, while MoO3 decreases the leakage current. Using the bilayer MoO3/CuI allows cumulating the advantages of each layer

Electropolymerization and Morphologic Characterization of α-Tetrathiophene

In this research, poly(α-tetrathiophene), poly(α-TTP), was potentiostatic and potentiodynamically electrosynthesized on Pt and F-doped SnO2 electrodes. The solvent effect (CH2Cl2 and CH3CN) on the nucleation and growth mechanism, NGM, and morphology of the respective deposit was established by potentiostatic method and scanning electron microscopy (SEM), respectively. Potentiodynamic electropolymerization at low sweep rates proved to favor the obtention of a polymer with a more uniform morphology and, in addition, its capacitance as capacitor increased and the p-doping/undoping relationship is close to one (reversible doping). On the other hand, when potentiostatic electropolymerization was realized, deconvolution of the obtained j/t transients revealed that under all conditions, the main contribution to electrolysis at high times (greater than 20 s) was instantaneous nucleation with 3D growth. Nevertheless, the contribution of instantaneous nucleation with 2D growth is always more important in the early stages of the process. However, regardless of the conditions employed in the electropolymerization, the use of an oligomer as starting unit, such as α-TTF, affords deposits with more homogeneous morphology than when the respective monomer is used. Therefore, the information gathered in the current work constitutes a significant contribution that validates the proposed model for the electropolymerization mechanism

Improvement of pentathiophene/fullerene planar heterojunction photovoltaic cells by improving the organic films morphology through the anode buffer bilayer

Organic photovoltaic cells (OPVCs) are based on a heterojunction electron donor (ED)/electron acceptor (EA). In the present work, the electron donor which is also the absorber of light is pentathiophene. The typical cells were ITO/HTL/pentathiophene/fullerene/Alq3/Al with HTL (hole transport layer) = MoO3, CuI, MoO3 /CuI. After optimisation of the pentathiophene thickness, 70 nm, the highest efficiency, 0.81%, is obtained with the bilayer MoO3/CuI as HTL. In order to understand these results the pentathiophene films deposited onto the different HTLs were characterized by scanning electron microscopy, atomic force microscopy, X-rays diffraction, optical absorption and electrical characterization. It is shown that CuI improves the conductivity of the pentathiophene layer through the modification of the film structure, while MoO3 decreases the leakage current. Using the bilayer MoO3/CuI allows cumulating the advantages of each layer

Optical fibers for endoscopic high-power Er:YAG laserosteotomy

ignificance: The highest absorption peaks of the main components of bone are in the mid-infrared region, making Er:YAG and CO2 lasers the most efficient lasers for cutting bone. Yet, studies of deep bone ablation in minimally invasive settings are very limited, as finding suitable materials for coupling high-power laser light with low attenuation beyond 2  μm is not trivial. Aim: The first aim of this study was to compare the performance of different optical fibers in terms of transmitting Er:YAG laser light with a 2.94-μm wavelength at high pulse energy close to 1 J. The second aim was to achieve deep bone ablation using the best-performing fiber, as determined by our experiments. Approach: In our study, various optical fibers with low attenuation (λ  =  2.94  μm) were used to couple the Er:YAG laser. The fibers were made of germanium oxide, sapphire, zirconium fluoride, and hollow-core silica, respectively. We compared the fibers in terms of transmission efficiency, resistance to high Er:YAG laser energy, and bending flexibility. The best-performing fiber was used to achieve deep bone ablation in a minimally invasive setting. To do this, we adapted the optimal settings for free-space deep bone ablation with an Er:YAG laser found in a previous study. Results: Three of the fibers endured energy per pulse as high as 820 mJ at a repetition rate of 10 Hz. The best-performing fiber, made of germanium oxide, provided higher transmission efficiency and greater bending flexibility than the other fibers. With an output energy of 370 mJ per pulse at 10 Hz repetition rate, we reached a cutting depth of 6.82  ±  0.99  mm in sheep bone. Histology image analysis was performed on the bone tissue adjacent to the laser ablation crater; the images did not show any structural damage. Conclusions: The findings suggest that our prototype could be used in future generations of endoscopic devices for minimally invasive laserosteotomy

Mo(SxOy) thin films deposited by electrochemistry for application in organic photovoltaic cells

In this study, Mo(SxOy) thin films were deposited onto fluorine doped tin oxide (FTO) using pulsed electrochemical deposition method. It is shown by scanning electron microscopy, energy-dispersive spectroscopy and X-ray photoelectron spectroscopy that after water cleaning the deposited Mo(SxOy) film corresponds to a hybrid layer MoSx:MoO3. This hybrid is used as anode buffer layer (ABL) in planar organic photovoltaic cells (OPVCs) based on the couple copper-phthalocyanine/fullerene. It is shown that it is necessary to proceed to a soft annealing-5 min at 150 °C- of the anode FTO/Mo(SxOy) to clean the ABL surface in order to obtain efficient contact with the organic material. The OPVC with the optimum Mo(SxOy) thickness, 12 nm, showed a power conversion efficiency, PCE = 1.41% under an illumination of AM1.5, which is 12% higher than that achieved with a simple MoO3 ABL. This improvement is attributed to the fact that using a hybrid MoS2:MoO3 ABL allows to combine the advantages of its both constituents. The MoSx blocks the electrons, while the high work function of MoO3 induces a high hole extraction efficiency at the interface electron donor/anode

Sintesis y propiedades fotovoltaicas de oligomero hexatienilenovinileno ralificado en celdas solares organicas con heterounion planar

A novel branched sexithienylene vinylene oligomer, (E)-Bis-1,2-(5,5´´-Dimethyl-(2,2´:3´,2´´- terthiophene)vinylene has been used as electron donor in a planar heterojunction Organic Photovoltaic cell (OPV). The electron acceptor was the fullerene (C60) and the cathode was an aluminum film, while ITO glass was used as anode. A hybrid anode buffer layer of MoO3 and CuI was used between the ITO glass and the electrodonor. The effect of the thickness of the branched sexithienylene vinylene film, thickness and deposit rate of CuI on the solar cells performances was studied. In the present work, it has been found that MoO3/CuI structure with 1.5 nm of CuI, deposited at 0.005 nm/s and the optimum branched sexithienylene vinylene thickness of 22 nm, efficiency (η) of 1.47 % could be achieved. This branched sixithienylene vinylene oligomer emerges as a promising electron donor compound which can be further be investigated in different combination of buffer layers and structures of OPV