Type I interferon promotes alveolar epithelial type II cell survival during pulmonary Streptococcus pneumoniae infection and sterile lung injury in mice

Protecting the integrity of the lung epithelial barrier is essential to ensure respiration and proper oxygenation in patients suffering from various types of lung inflammation. Type I interferon (IFN‐I) has been associated with pulmonary epithelial barrier function, however, the mechanisms and involved cell types remain unknown. We aimed to investigate the importance of IFN‐I with respect to its epithelial barrier strengthening function to better understand immune‐modulating effects in the lung with potential medical implications. Using a mouse model of pneumococcal pneumonia, we revealed that IFN‐I selectively protects alveolar epithelial type II cells (AECII) from inflammation‐induced cell death. Mechanistically, signaling via the IFN‐I receptor on AECII is sufficient to promote AECII survival. The net effects of IFN‐I are barrier protection, together with diminished tissue damage, inflammation, and bacterial loads. Importantly, we found that the protective role of IFN‐I can also apply to sterile acute lung injury, in which loss of IFN‐I signaling leads to a significant reduction in barrier function caused by AECII cell death. Our data suggest that IFN‐I is an important mediator in lung inflammation that plays a protective role by antagonizing inflammation‐associated cell obstruction, thereby strengthening the integrity of the epithelial barrier.     

Germanium Nanoparticles Prepared by Laser Ablation in Low Pressure Helium and Nitrogen Atmosphere for Biophotonic Applications

Due to particular physico-chemical characteristics and prominent optical properties, nanostructured germanium (Ge) appears as a promising material for biomedical applications, but its use in biological systems has been limited so far due to the difficulty of preparation of Ge nanostructures in a pure, uncontaminated state. Here, we explored the fabrication of Ge nanoparticles (NPs) using methods of pulsed laser ablation in ambient gas (He or He-N₂ mixtures) maintained at low residual pressures (1–5 Torr). We show that the ablated material can be deposited on a substrate (silicon wafer in our case) to form a nanostructured thin film, which can then be ground in ethanol by ultrasound to form a stable suspension of Ge NPs. It was found that these formed NPs have a wide size dispersion, with sizes between a few nm and hundreds of nm, while a subsequent centrifugation step renders possible the selection of one or another NP size fraction. Structural characterization of NPs showed that they are composed of aggregations of Ge crystals, covered by an oxide shell. Solutions of the prepared NPs exhibited largely dominating photoluminescence (PL) around 450 nm, attributed to defects in the germanium oxide shell, while a separated fraction of relatively small (5–10 nm) NPs exhibited a red-shifted PL band around 725 nm under 633 nm excitation, which could be attributed to quantum confinement effects. It was also found that the formed NPs exhibit high absorption in the visible and near-IR spectral ranges and can be strongly heated under photoexcitation in the region of relative tissue transparency, which opens access to phototherapy functionality. Combining imaging and therapy functionalities in the biological transparency window, laser-synthesized Ge NPs present a novel promising object for cancer theranostics.     

Pediatric and adolescent injury in rodeo

ABSTRACT

High injury potential in rodeo is well recognized but the injury data for pediatric and adolescent rodeo athletes remain sparse. A systematic review of the literature published between 1990 and 2017 was conducted to assess the incidence and determinants of rodeo-related injuries in this population and to suggest injury prevention measures. Three of the 10 included studies reported event frequency and exposure data while the other seven pertained to particular injuries and/or rodeo events. Although each study documented cases of severe injuries, the limited epidemiological data indicated the majority of pediatric and adolescent athletes sustained minor injuries, such as sprains, strains, and contusions. Most injuries resulted from the impact of a fall or animal contact with the head being the most reported injury site. Owing to an unpredictable nature of this sport, injury prevention is challenging but there is evidence that helmets reduce the incidence and severity of head injuries.     

The hybrid technique of pelvic organ prolapse treatment: apical sling and subfascial colporrhaphy

Introduction and hypothesis

The majority of patients with cystocele undergoing reconstructive surgery have combined defects of pubocervical fascia and uterosacral/cardinal ligament complex. In this regard, the simultaneous correction of both defects is rational. Furthermore, decreasing the use of synthetic materials in pelvic floor surgery is an important goal. The aim was to evaluate the objective and subjective cure rate of a hybrid technique: bilateral sacrospinous fixation using modern monofilament synthetic tape (apical sling) combined with the original technique of subfascial colporrhaphy.

Materials and methods

This prospective study involved 148 women suffering from cystocele combined with apical prolapse. We used the following criteria to evaluate the results of surgical treatment: results of the vaginal examination (POP-Q system), urodynamic tests, bladder ultrasound, special questionnaires (Pelvic Floor Distress Inventory [PFDI-20], Pelvic Floor Impact Questionnaire [PFIQ-7], Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire [PISQ-12], International Consultation on Incontinence Modular Questionnaire Short Form [ICIQ-SF]). All listed parameters were determined before the surgery and at control examinations at 1, 6, and 12 months after the treatment.

Results

At the 1-year follow-up, the objective cure rate for prolapse was 97.8%. The rate of anatomical recurrence was 2.2% (3 out of 138). The following long-term complications were noted: de novo urgency and stress urinary incontinence de novo in 2 (1.4%) and 4 (2.9%) patients, respectively. Comparison of the scores by the questionnaires also revealed a significant improvement in the quality of life in the postoperative period. Patient satisfaction rate was 97.1%.

Conclusion

The hybrid technique is an effective and safe uterus-sparing method for patients with advanced forms of cystocele combined with apical prolapse. This technique improves voiding function, quality of life, and provides a high satisfaction rate.

     

Selection for tameness,a key behavioral trait of domestication,increases adult hippocampal neurogenesis in foxes

Work on laboratory and wild rodents suggests that domestication may impact on the extent of adult hippocampal neurogenesis and its responsiveness to regulatory factors. There is, however, no model of laboratory rodents and their nondomesticated conspecifics that would allow a controlled comparison of the effect of domestication. Here, we present a controlled within‐species comparison of adult hippocampal neurogenesis in farm‐bred foxes (Vulpes vulpes) that differ in their genetically determined degree of tameness. Quantitative comparisons of cell proliferation (Ki67) and differentiating cells of neuronal lineage (doublecortin, DCX) in the hippocampus of foxes were performed as a proxy for neurogenesis. Higher neurogenesis was observed in tameness‐selected foxes, notably in an extended subgranular zone of the middle and temporal compartments of the hippocampus. Increased neurogenesis is negatively associated with aggressive behavior. Across all animals, strong septotemporal gradients were found, with higher numbers of proliferating cells and young neurons relative to resident granule cells in the temporal than in the septal hippocampus. The opposite gradient was found for the ratio of DCX /Ki67‐ positive cell s. When tameness‐selected and unselected foxes are compared with rodents and primates, proliferation is similar, while the number of young neurons is higher. The difference may be mediated by an extended period of differentiation or higher rate of survival. On the background of this species‐specific neurogenic pattern, selection of foxes for a single behavioral trait key to domestication, i.e. genetic tameness, is accompanied by global and region‐specific increases in neurogenesis. © 2015 Wiley Periodicals, Inc.     

Luminescence and photoelectrochemical properties of size-selected aqueous copper-doped Ag–In–S quantum dots

Ternary luminescent copper and silver indium sulfide quantum dots (QDs) can be an attractive alternative to cadmium and lead chalcogenide QDs. The optical properties of Cu–In–S and Ag–In–S (AIS) QDs vary over a broad range depending on the QD composition and size. The implementation of ternary QDs as emitters in bio-sensing applications can be boosted by the development of mild and reproducible syntheses directly in aqueous solutions as well as the methods of shifting the photoluminescence (PL) bands of such QDs as far as possible into the near IR spectral range. In the present work, the copper-doping of aqueous non-stoichiometric AIS QDs was found to result in a red shift of the PL band maximum from around 630 nm to ∼780 nm and PL quenching. The deposition of a ZnS shell results in PL intensity recovery with the highest quantum yield of 15%, with almost not change in the PL band position, opposite to the undoped AIS QDs. Size-selective precipitation using 2-propanol as a non-solvent allows discrimination of up to 9 fractions of Cu-doped AIS/ZnS QDs with the average sizes in the fractions varying from around 3 to 2 nm and smaller and with reasonably the same composition irrespective of the QD size. The decrease of the average QD size results in a blue PL shift yielding a series of bright luminophors with the emission color varies from deep-red to bluish-green and the PL efficiency increases from 11% for the first fraction to up to 58% for the smallest Cu-doped AIS/ZnS QDs. The rate constant of the radiative recombination of the size-selected Cu-doped AIS/ZnS QDs revealed a steady growth with the QD size decrease as a result of the size-dependent enhancement of the spatial exciton confinement. The copper doping was found to result in an enhancement of the photoelectrochemical activity of CAIS/ZnS QDs introduced as spectral sensitizers of mesoporous titania photoanodes of liquid-junction solar cells.

Colloidal size-selected copper-doped Ag–In–S quantum dots were produced directly in aqueous solutions by fractionation/redispersion with a plethora of emission colors and a top luminescence quantum yield of around 60%.     

Uncharged AZT and D4T derivatives of phosphonoformic and phosphonoacetic acids as anti-HIV pronucleosides

Two series of new lipophilic phosphonoformate and phosphonoacetate derivatives of AZT and d4T were synthesized and evaluated as anti-HIV agents. The efficacy of some of the synthesized compounds in cell cultures infected with HIV-1 was higher than that of the parent nucleosides and only slightly correlated to their stability in the phosphate buffer and human blood serum. The synthesized phosphonates are most probably prodrug forms of the corresponding nucleosides.     

Newly synthesised oxime and lactone derivatives from Dipterocarpus alatus dipterocarpol as anti-diabetic inhibitors: experimental bioassay-based evidence and theoretical computation-based prediction

Dipterocarpus alatus-derived products are expected to exhibit anti-diabetes properties. Natural dipterocarpol (1) was isolated from Dipterocarpus alatus collected in Quang Nam province, Vietnam; afterwards, 20 derivatives including 13 oxime esters (2 and 3a–3m) and 7 lactones (4, 5, 6a–6e) were semi-synthesised. Their inhibitory effects towards diabetes-related proteins were investigated experimentally (α-glucosidase) and computationally (3W37, 3AJ7, and PTP1B). Except for compound 2, the other 19 compounds (3a–3m, 4, 5, and 6a–6d) are reported for the first time, which were modified at positions C-3, C-24 and C-25 of the dipterocarpol via imidation, esterification, oxidative cleavage and lactonisation reactions. A framework based on docking-QSARIS combination was proposed to predict the inhibitory behaviour of the ligand-protein complexes. Enzyme assays revealed the most effective α-glucosidase inhibitors, which follow the order 5 (IC₅₀ of 2.73 ± 0.05 μM) > 6c (IC₅₀ of 4.62 ± 0.12 μM) > 6e (IC₅₀ of 7.31 ± 0.11 μM), and the computation-based analysis confirmed this, i.e., 5 (mass: 416.2 amu; polarisability: 52.4 ų; DS: −14.9 kcal mol⁻¹) > 6c (mass: 490.1 amu; polarisability: 48.8 ų; DS: −13.7 kcal mol⁻¹) > 6e (mass: 549.2 amu; polarisability: 51.6 ų; DS: −15.2 kcal mol⁻¹). Further theoretical justifications predicted 5 and 6c as versatile anti-diabetic inhibitors. The experimental results encourage next stages for the development of anti-diabetic drugs and the computational strategy invites more relevant work for validation.

Dipterocarpus alatus-derived products are expected to exhibit anti-diabetes properties.