The transition from salt-in-water to water-in-salt nanostructures in water solutions of organic ionic liquids relevant for biological applications.

The nanostructure in water solutions of three organic ionic liquids relevant for biological applications has been studied by molecular dynamics simulations based on empirical force fields. The three compounds consisted of two different triethylammonium salts, known to affect the fibrillation kinetics of Aß peptides, and a phosphonium dication, which has been shown to possess a marked bactericidal activity. The structure of solutions spanning a wide concentration range (from 25 to 75 wt%) has been analysed by computing several combinations of partial structure factors, measuring the fluctuation of the ion and water distribution in space. At moderate salt concentration, the results reflect the formation in water of salt-rich domains of nanometric size. With salt concentration increasing beyond 50 wt%, the system enters the so-called water-in-salt regime, in which the aggregation properties of water become relevant, giving origin to water-rich domains in the nearly uniform salt environment. The persistence over a wide concentration range of nearly integer (∼6; ∼4) water-ion coordination numbers suggests the formation of stoichiometric liquid ionic hydrates.

Chronic hepatitis C infection and liver disease in HIV-coinfected patients in Asia.

Data on markers of hepatitis C virus (HCV) disease in HIV-HCV-coinfected patients in resource-limited settings are scarce. We assessed HCV RNA, HCV genotype (GT), IL28B GT and liver fibrosis (FibroScan® ) in 480 HIV-infected patients with positive HCV antibody in four HIV treatment centres in South-East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median (IQR) age was 38.1 (34.7-42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median (IQR) CD4 count was 446 (325-614) cells/mm3 and 208 (94.1%) of 221 patients tested had HIV-1 RNA <400 copies/mL. A total of 412 (85.8%) had detectable HCV RNA, at a median (IQR) of 6.2 (5.4-6.6) log10 IU/mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, eight (2.1%) had GT4, two (0.5%) had GT2, and seven (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan® , 143 (37.6%) had no/mild liver fibrosis (F0-F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan® failure. In conclusion, a high proportion of HIV-HCV-coinfected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (≥F2).

Erythrocyte heat shock protein responses to chronic (in vivo) and acute (in vitro) temperature challenge in diploid and triploid salmonids.

This research investigated how ploidy level (diploid versus triploid) affects the heat shock protein (HSP) response in erythrocytes under different thermal stress regimes, both in vivo and in vitro, in Atlantic salmon (Salmo salar) and brook charr (Salvelinus fontinalis) in order to address the question of why triploids typically have reduced thermal tolerance. A preliminary study confirmed that identical volumes of diploid and triploid erythrocytes (which equates to a smaller number of larger cells for triploids compared to diploids) did not differ in total protein synthesis rates. After chronic (100d) acclimation of fish to 5, 15 and 25°C, triploid erythrocytes had lower HSP70, HSP90, heat shock factor 1 (HSF1) and ubiquitin (free and total) levels than diploids in both species. Furthermore, Atlantic salmon erythrocytes showed significantly higher protein breakdown (based on conjugated ubiquitin levels) in triploids than diploids after acute heat stress in vitro, but no significant difference was detected between ploidies after acute cold stress. These results indicate that: 1) triploid erythrocytes synthesize more total protein per cell than diploids as a result of increased cell size; 2) triploids have sufficient total HSP levels for survival under low stress conditions; and 3) the lower basal titres of HSPs in triploids may be a handicap when combating acute stress. Taken together, this suggests that triploids are limited in their ability to withstand thermal stress because of a reduced ability to maintain proteostasis under stressful conditions.

Mmp25ß facilitates elongation of sensory neurons during zebrafish development.

Matrix metalloproteinases (MMPs) are a large and complex family of zinc-dependent endoproteinases widely recognized for their roles in remodeling the extracellular matrix (ECM) during embryonic development, wound healing, and tissue homeostasis. Their misregulation is central to many pathologies, and they have therefore been the focus of biomedical research for decades. These proteases have also recently emerged as mediators of neural development and synaptic plasticity in vertebrates, however, understanding of the mechanistic basis of these roles and the molecular identities of the MMPs involved remains far from complete. We have identified a zebrafish orthologue of mmp25 (a.k.a. leukolysin; MT6-MMP), a membrane-type, furin-activated MMP associated with leukocytes and invasive carcinomas, but which we find is expressed by a subset of the sensory neurons during normal embryonic development. We detect high levels of Mmp25ß expression in the trigeminal, craniofacial, and posterior lateral line ganglia in the hindbrain, and in Rohon-Beard cells in the dorsal neural tube during the first 48 h of embryonic development. Knockdown of Mmp25ß expression with morpholino oligonucleotides results in larvae that are uncoordinated and insensitive to touch, and which exhibit defects in the development of sensory neural structures. Using in vivo zymography, we observe that Mmp25ß morphant embryos show reduced Type IV collagen degradation in regions of the head traversed by elongating axons emanating from the trigeminal ganglion, suggesting that Mmp25ß may play a pivotal role in mediating ECM remodeling in the vicinity of these elongating axons.

Spontaneous dormancy of metastatic breast cancer cells in an all human liver microphysiologic system.

BACKGROUND: Metastatic outgrowth in breast cancer can occur years after a seeming cure. Existing model systems of dormancy are limited as they do not recapitulate human metastatic dormancy without exogenous manipulations and are unable to query early events of micrometastases. METHODS: Here, we describe a human ex vivo hepatic microphysiologic system. The system is established with fresh human hepatocytes and non-parenchymal cells (NPCs) creating a microenvironment into which breast cancer cells (MCF7 and MDA-MB-231) are added. RESULTS: The hepatic tissue maintains function through 15 days as verified by liver-specific protein production and drug metabolism assays. The NPCs form an integral part of the hepatic niche, demonstrated within the system through their participation in differential signalling cascades and cancer cell outcomes. Breast cancer cells intercalate into the hepatic niche without interfering with hepatocyte function. Examination of cancer cells demonstrated that a significant subset enter a quiescent state of dormancy as shown by lack of cell cycling (EdU(-) or Ki67(-)). The presence of NPCs altered the cancer cell fraction entering quiescence, and lead to differential cytokine profiles in the microenvironment effluent. CONCLUSIONS: These findings establish the liver microphysiologic system as a relevant model for the study of breast cancer metastases and entry into dormancy.

Ni doping induced property enhancement in laser ablated BaSnO3 films suitable for optoelectronic applications.

Pulsed laser deposition is a straightforward approach for preparing films with superconducting to dielectric properties with atomic layer precision. The deep-seated mechanisms involved in the particle transport from target to substrate and subsequent film formation still need to be fully comprehended. This manuscript reports the property enhancement observed in laser ablated perovskite BaSnO3 films with Ni doping. Films' crystallinity improvement is observed, and an intensity enhancement of 1150% is observed on 3 mol% Ni-doping. The optimum Ni-doping concentration in BaSnO3 is found to be 3 mol%. Herein, Ni-doped BaSnO3 films deposited by PLD showed an unusual increase in film thickness (i.e., from 615 nm in the pure film to 1317 nm in the film with 7 mol% Ni-doping as revealed by lateral SEM analysis and spectroscopic ellipsometry). We propose an "Induced Magnetic field-assisted Particle Convergence (IMPC)" effect for this superficial growth enhancement. The film's optical properties are modified with an increased nickel doping level, and the bandgap energy shows renormalization. All the films show excellent transmittance (80-90%) in the Vis.-NIR region. Hall-effect measurement reveals the increased carrier concentration by three orders (2.98 × 1011 to 3.50 × 1014 cm-3). In addition, the enhancement in mobility from 3.13 to 20.93 cm2V-1s-1 and a decrease in electrical resistivity by six orders (i.e., from 4.05 × 109 to 1.13 × 103 Ω cm) are observed on 7 mol% Ni doping. XPS measurements reveals that the Ba, Sn and Ni ions are at 2+, 4+ and 2+ oxidation states. Using spectroscopic ellipsometric method, we estimated the optical constants of the films, the refractive index, dielectric constant, and extinction coefficient show a normal dispersion behavior. The high crystallinity, high transmittance, suitable surface topography, and improved electrical performances of the Ni-doped BaSnO3 films make them excellent candidates for optoelectronic devices and solar cells.

Persistent left fifth aortic arch with pentalogy of Fallot.

Congenital double-lumen aortic arch resulting from persistence of the fifth aortic arterial arch (PFAA) is a rare congenital anomaly. It appears as a vascular structure running inferior and parallel to the "real" aortic arch from the innominate artery to the left subclavian artery. We report a case of persistent fifth aortic arch (systemic-to-systemic arterial connection) with pentalogy of Fallot in a patient who underwent successful intracardiac repair with a transannular patch with very proximal aortic cannulation for cardiopulmonary bypass (CPB).

SARS-Coronavirus 2, A Metabolic Reprogrammer: A Review in the Context of the Possible Therapeutic Strategies.

Novel coronavirus, SARS-CoV-2, is advancing at a staggering pace to devastate the health care system and foster concerns over public health. In contrast to the past outbreaks, coronaviruses are not clinging themselves as a strict respiratory virus. Rather, becoming a multifaceted virus, it affects multiple organs by interrupting a number of metabolic pathways leading to significant rates of morbidity and mortality. Following infection, they rigorously reprogram multiple metabolic pathways of glucose, lipid, protein, nucleic acid, and their metabolites to extract adequate energy and carbon skeletons required for their existence and further molecular constructions inside a host cell. Although the mechanism of these alterations is yet to be known, the impact of these reprogramming is reflected in the hyperinflammatory responses, so called cytokine storm and the hindrance of the host immune defence system. The metabolic reprogramming during SARSCoV- 2 infection needs to be considered while devising therapeutic strategies to combat the disease and its further complication. The inhibitors of cholesterol and phospholipids synthesis and cell membrane lipid raft of the host cell can, to a great extent, control the viral load and further infection. Depletion of energy sources by inhibiting the activation of glycolytic and hexosamine biosynthetic pathways can also augment antiviral therapy. The cross talk between these pathways also necessitates the inhibition of amino acid catabolism and tryptophan metabolism. A combinatorial strategy that can address the cross talks between the metabolic pathways might be more effective than a single approach, and the infection stage and timing of therapy will also influence the effectiveness of the antiviral approach. We herein focus on the different metabolic alterations during the course of virus infection that help exploit the cellular machinery and devise a therapeutic strategy that promotes resistance to viral infection and can augment body's antivirulence mechanisms. This review may cast light on the possibilities of targeting altered metabolic pathways to defend against virus infection in a new perspective.

Absorption of Phosphonium Cations and Dications into a Hydrated POPC Phospholipid Bilayer: A Computational Study.

Molecular dynamics (MD) based on an empirical force field is applied to investigate the effect of phosphonium cations ([P6,6,6,6]+) and geminal dications ([DxC10]2+) inserted at T = 300 K into the hydration layer separating planar POPC phospholipid bilayers. Up to high concentration, nearly every added cation and dication becomes absorbed into the lipid phase. Absorption takes place during several microseconds and is virtually irreversible. The neutralizing counterions ([Cl]-, in the present simulation) remain dissolved in water, giving origin to the charge separation and the strong electrostatic double layer at the water/lipid interface. Incorporation of cations and dications changes the properties of the lipid bilayer such as diffusion, viscosity, and the electrostatic pattern. At high ionic concentration, the bilayer acquires a long-wavelength standing undulation, corresponding to a change of phase from fluid planar to ripple. All these changes are potentially able to affect processes relevant in the context of cell biology. The major difference between cations and dications concerns the kinetics of absorption, which takes place nearly two times faster in the [P6,6,6,6]+ case, and for [DxC10]2+ dications displays a marked separation into two-stages, corresponding to the easy absorption of the first phosphonium head of the dication and the somewhat more activated absorption of the second phosphonium head of each dication.

Histo-morphologic and gravimetric changes of teeth exposed to high temperatures - An in-vitro study.

BACKGROUND: Fire intelligence is the multidisciplinary basis of reconnaissance, which includes determining the origin, cause, and identification of fire victims. Fire is a destructive force capable of inflicting significant damage. Destruction of soft tissue in fire disasters makes victim identification nearly impossible. Teeth are hard and resilient and withstand such conditions. Analyzing the precise morphological, stereomicroscopic, histological, and gravimetric findings can extract valuable information from dental evidence in forensic investigations. MATERIALS AND METHODS: Thirty-six mandibular premolar teeth extracted for therapeutic purposes were exposed to high-temperature gradients. Macroscopic, stereomicroscopic, histological, and dry weight analyses were performed at each temperature gradient. RESULTS: The colour of teeth changed from yellowish orange to metallic black bronze to chalky white. Stereomicroscopy showed intact teeth at 100°C, gradual micro-cracks at 500°C, and a fully fractured crown at 900°C. Decalcified sections revealed dilatation of dentinal tubular pattern at 300°C. Dentinal tubules showed appearance of vapour bubbles at 400°C, resulting in loss of typical architecture. In the ground sections, alterations in scalloping nature of dentino-enamel junction, coalescing radicular dentinal tubules, and sand cracking appearance of teeth were noted at 100°C, 300°C, and 900°C, respectively. Significant reductions in the weight of the teeth samples were observed with higher temperatures. CONCLUSION: From the morphological, histological, and gravimetric changes in a tooth caused by fire, it might be possible to determine the temperature and duration of fire exposure, and the cause of the fire.

Tailoring the Emission Behavior of WO3 Thin Films by Eu3+ Ions for Light-Emitting Applications.

The article reports the successful fabrication of Eu3+-doped WO3 thin films via the radio-frequency magnetron sputtering (RFMS) technique. To our knowledge, this is the first study showing the tunable visible emission (blue to bluish red) from a WO3:Eu3+ thin film system using RFMS. X-ray diffractograms revealed that the crystalline nature of these thin films increased upto 3 wt% of the Eu3+ concentration. The diffraction peaks in the crystalline films are matched well with the monoclinic crystalline phase of WO3, but for all the films', micro-Raman spectra detected bands related to WO3 monoclinic phase. Vibrational and surface studies reveal the amorphous/semi-crystalline behavior of the 10 wt% Eu3+-doped sample. Valence state determination shows the trivalent state of Eu ions in doped films. In the 400-900 nm regions, the fabricated thin films show an average optical transparency of ~51-85%. Moreover, the band gap energy gradually reduces from 2.95 to 2.49 eV, with an enhancement of the Eu3+-doping content. The doped films, except the one at a higher doping concentration (10 wt%), show unique emissions of Eu3+ ions, besides the band edge emission of WO3. With an enhancement of the Eu3+ content, the concentration quenching process of the Eu3+ ions' emission intensities is visible. The variation in CIE chromaticity coordinates suggest that the overall emission color can be altered from blue to bluish red by changing the Eu3+ ion concentration.

Development of a Low-cost NGS Test for the Evaluation of Thyroid Nodules.

Ultrasound-guided fine needle aspiration cytology (FNAC) is the preferred method of identifying malignancy in palpable thyroid nodules using the Bethesda reporting system. However, in around 30-40% of FNACs (Bethesda categories III, IV, and V), the results are indeterminate and surgery is required to confirm malignancy. Out of those who undergo surgery, only 10-40% of patients in these categories are found to have malignancies, thus proving surgery to be unnecessary for some patients or to be incomplete in others. While molecular testing on thyroid FNAC material is part of the American Thyroid Association (ATA) guidelines in evaluating thyroid nodules, it is currently unavailable in India due to cost constraints. In this study, we prospectively collected FNAC samples from sixty-nine patients who presented with palpable thyroid nodules. We designed a cost-effective next-generation sequencing (NGS) test to query multiple variants in the DNA and RNA isolated from the fine needle aspirate. The identification of oncogenic variants was considered to be indicative of malignancy, and confirmed by surgical histopathology. The panel showed an overall sensitivity of 81.25% and a specificity of 100%, while in the case of Bethesda categories III, IV, and V, the sensitivity was higher (87.5%) and the specificity was established at 100%. The panel could thereby serve as a rule-in test for the diagnosis of thyroid cancer and therefore help identify patients who require surgery, especially in the indeterminate Bethesda categories III, IV, and V.

[Severe airway distress following cervical spine operation: retrospective breakdown of the chain of errors]. / Dramatischer Atemwegsnotfall nach Operation an der Halswirbelsäule : Retrospektive Analyse der Fehlerkette.

A 71-year-old female patient received a prothesis due to a cervical disc prolapsed and bleeding into the collar soft tissues occurred postoperatively. Following a computed tomography examination severe peracute respiratory decompensation occurred while administering topical anesthesia to the pharynx in order to perform fiber optic intubation. Endotracheal intubation using conventional laryngoscopy was unsuccessful and the patient required immediate cricothyroidotomy. As an on-site cricothyrotomy set to establish a secure airway was not available the decision was taken to perform surgical cricothyroidotomy. As a conclusion to this life-threatening event in the case of symptoms, such as dyspnea, dysphonia and dysphagia after operations of the cervical spine the airway has to be secured early and according to the local algorithm.

Micro-structural, electrical and spectroscopic investigations of pulsed laser ablated palladium incorporated nanostructured tungsten oxide films.

Pure and Pd incorporated (0.5, 1 and 5 wt%) WO3 films are prepared on quartz substrates using pulsed laser ablation (PLD) technique in an oxygen ambient of 0.12 mbar, at a substrate temperature (Ts) of 873 K. Palladium incorporation effects on the microstructure, optical and electrical properties of tungsten oxide films are systematically investigated using techniques like X-ray diffraction (XRD), Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM), Energy dispersive X-ray spectroscopy (EDX), micro-Raman spectroscopy, UV-Vis absorption spectroscopy and temperature dependent electrical resistivity measurements. The micro-structural analysis by XRD and micro-Raman indicates that Pd addition can perturb the tungsten oxide lattice and suppress the grain growth. Optical band gap values of the films increases from 3.17 eV for pure WO3 to 3.29 eV for 5 wt% Pd incorporated WO3 films. All the films present high transparency in the visible spectral range. The electrical resistivity studies of the pure and Pd incorporated films done at room temperature and for the range of temperature; 170-450 K reveal that Pd addition can lower the resistivity of the WO3 thin films. Room temperature resistivity as well as activation energy of the film decreases exponentially with Pd incorporation concentration. Highly transparent, nanocrystalline and semiconducting WO3 films with low resistivity obtained by Pd incorporation can make WO3 suitable for microelectronics industry and for gas sensing applications.

Effect of zinc oxide doping on the structural and optical characterization of nanostructured molybdenum oxide films.

Undoped and zinc oxide (ZnO) doped molybdenum oxide (MoO3) films were prepared by RF magnetron sputtering technique. The influence of doping and post annealing temperature on the structural and optical properties of these films were investigated systematically using X-ray diffraction (XRD), energy dispersive X-ray analysis (EDAX), scanning electron microscopy (SEM), atomic force microscopy (AFM), UV-VIS spectroscopy and photoluminescence spectroscopy (PL). The XRD patterns indicate the presence of stoichiometric orthorhombic alpha-MoO3 phase in the annealed (573 and 673 K) undoped molybdenum oxide films and in ZnO doped molybdenum oxide film (annealed at 673 K). The crystalline grain size in the films was investigated using Debye Scherrer formula and corrected using Hall-Williamson equation. The SEM and AFM images revealed the distribution of nano leafs, nanorods and nanograins. Nanorods of length 1.4 microm and diameter 149 nm can be observed in ZnO doped films. The optical band gap energy was found to increase with increase in annealing temperature and particle size. These nanostructures show a room temperature PL emission in the UV and visible region.

Ag@Nb2O5 plasmonic blocking layer for higher efficiency dye-sensitized solar cells.

Engineering photons on a nanoscale via guidance and localization by metal nanostructures has a profound influence on the performance of devices that try to mimic the process of photosynthesis. The conventional route for the synthesis of plasmonic nanoparticles and their integration into the porous structure of the photoanode either directly or after being capped with a dielectric material not only adds to the complexity but also to the cost of the cell. The present study introduces the concept of a plasmonic blocking layer that concurrently acts as a light harvester and an electron-blocking layer in a dye-sensitized solar cell (DSSC), wherein the plasmonic silver nanoparticles are incorporated into an Nb2O5 blocking layer by a simple one-step process. The cell with the plasmonic blocking layer achieves an efficiency of 9.24% when compared with a cell with a non-plasmonic blocking layer (7.6%), registering an impressive enhancement in the efficiency by 22%. Moreover, the cell with the plasmonic blocking layer shows an improvement in the efficiency by 49% when compared with the cell without a blocking layer (6.19%).

Silver nanoparticles-incorporated Nb2O5 surface passivation layer for efficiency enhancement in dye-sensitized solar cells.

Guiding and capturing photons at the nanoscale by means of metal nanoparticles and interfacial engineering for preventing back-electron transfer are well documented techniques for performance enhancement in excitonic solar cells. Drifting from the conventional route, we propose a simple one-step process to integrate both metal nanoparticles and surface passivation layer in the porous photoanode matrix of a dye-sensitized solar cell. Silver nanoparticles and Nb2O5 surface passivation layer are simultaneously deposited on the surface of a highly porous nanocrystalline TiO2 photoanode, facilitating an absorption enhancement in the 465 nm and 570 nm wavelength region and a reduction in back-electron transfer in the fabricated dye-sensitized solar cells together. The TiO2 photoanodes were prepared by spray pyrolysis deposition method from a colloidal solution of TiO2 nanoparticles. An impressive 43% enhancement in device performance was accomplished in photoanodes having an Ag-incorporated Nb2O5 passivation layer as against a cell without Ag nanoparticles. By introducing this idea, we were able to record two benefits - the metal nanoparticles function as the absorption enhancement agent, and the Nb2O5 layer as surface passivation for TiO2 nanoparticles and as an energy barrier layer for preventing back-electron transfer - in a single step.