Reduced Work Function in Anatase ⟨101⟩ TiO2 Films Self-Doped by O-Vacancy-Dependent Ti3+ Bonds Controlling the Photocatalytic Dye Degradation Performance.

TiO2 has the proven capability of catalytically decomposing pollutants under light illumination, thereby embracing potential applications in wastewater management. The photocatalytic dye degradation activity is largely controlled by the optical band gap that dictates the extent of electron-hole pair generation via photon absorption, and the recombination kinetics of charges. In this context, the material's work function governs how easily the charge carriers can be transferred at the dye-adsorbed photocatalytically active sites. Accordingly, nanocrystalline TiO2 thin films are grown in the anatase phase with ⟨101⟩ orientation, using RF magnetron sputtering at 200 °C. Besides studying the film's structural morphology, optical band gap, and elemental composition, the electronic properties are extensively investigated. The work function of the material was controlled by varying the O-vacancy-dependent Ti3+ bonding configuration in the network. It has been demonstrated how the photocatalytic methylene blue dye degradation activity of the nanocrystalline TiO2 films of predominantly the anatase phase improves on reducing the sputtering pressure during deposition. At a low deposition pressure of 20 mTorr, a low work function of ∼4.2 eV of the film, resulting from the formation of a Ti3+-bond through the O vacancies in the network, potentially increases its carrier lifetime and delivers the superior photocatalytic activity (∼82.7% dye degradation with a rate constant of k ∼ 0.0073 min-1) via silently facilitating fast electron transfer from the photocatalyst to the dye in the aqueous solution. The higher stoichiometric film prepared at p = 40 mTorr exhibits an inferior photocatalytic activity (∼20.4% dye degradation with a rate constant of k ∼ 0.0009 min-1), as retarded by its higher work function of ∼4.62 eV, despite retaining a relatively low band gap. Thus, without using any heterojunction or extrinsically doped photocatalyst, the dye degradation can be controlled simply by reducing the work function of nanocrystalline TiO2 thin films via controlling the O-vacancy-dependent Ti3+ bonding in its self-doped network.

Chemometric profiling and anti-arthritic activity of aerial parts of Glinus oppositifolius (L.) Aug. DC.

ETHNOPHARMACOLOGICAL RELEVANCE: Glinus oppositifolius (L.) Aug. DC. belongs to the family Molluginaceae, an annual prostrate herb traditionally used to treat inflammations, arthritis, malarial, wounds, fevers, diarrhoea, cancer, stomach discomfort, jaundice, and intestinal parasites. However, the anti-arthritic activity of the aerial part has still not been reported. AIM OF THE STUDY: To investigate the antioxidant and anti-arthritic activity of G. oppositifolius in Complete Freund's Adjuvant (CFA) induced rats. MATERIALS AND METHODS: The dried aerial parts of this plant material were defatted with n-hexane and extracted by methanol using a soxhlet apparatus. The in vitro anti-arthritic activity of methanolic extract of G. oppositifolius (MEGO) was evaluated in protein denaturation, membrane stabilization, and inhibition of proteinase assay at 25, 50, 100, 200, and 400 µg/ml concentrations. Female Wistar rats were immunized sub-dermally into the right hind paw with 0.1 ml of CFA. Rats were administered with MEGO at doses of 200 and 400 mg/kg once daily for fourteen days after arthritis induction. Assessment of arthritis was performed by measuring paw diameter, arthritic index, arthritic score, body weight, organ weight, and hematological and biochemical parameters, followed by the analysis of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin-1-beta (IL-1ß), cyclooxygenase-2 (COX-2), interleukin 13 (IL-13) and interleukin 10 (IL-10) and histopathological study. In vivo antioxidant effect was investigated in enzymatic assays. The presence of phytoconstituents was analyzed by Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS), respectively. In silico molecular docking study of the compounds was carried out against COX-2, IL-1ß, IL-6, and TNF-α using AutoDock 4.2 and BIOVIA-Discovery Studio Visualizer software. RESULTS: MEGO's in vitro anti-arthritic activity showed dose-dependent inhibition of protein denaturation, membrane stabilization, and proteinase inhibition, followed by significant in vivo anti-arthritic activity. The rats treated with MEGO showed tremendous potential in managing arthritis-like symptoms by restoring hematological, biochemical, and histological changes in CFA-induced rats. MEGO (200 and 400 mg/kg) showed a significant alleviation in the levels of hyper expressed inflammatory mediators (TNF-α, IL-1ß, and IL-6) and oxidative stress (SOD, CAT, GSH, and LPO) in CFA-induced rats. Spergulagenin-A as identified by LC-MS analysis, exhibited the highest binding affinity against COX-2 (-8.6), IL-1ß (7.2 kcal/mol), IL-6 (-7.4 kcal/mol), and TNF-α (-6.5 kcal/mol). CONCLUSIONS: Provided with the comprehensive investigation, methanolic extract of G. oppositifolius against arthritic-like condition is a proof of concept that revalidates its ethnic claim. The presence of Spergulagenin-A might be responsible for the anti-arthritic activity.

A recent update on drugs and alternative approaches for parkinsonism.

Parkinson's disease, often known as PD, is a more common age-related neurological disorder that affects a huge number of older adults worldwide. Parkinson's disease is predominantly a movement-related pathosis and is distinguished by the deposition of intra-neuronal aggregates, as the alpha-synuclein gene is expressed as Lewy bodies (LB) causing dopaminergic neurons to die. Stress in early life may contribute to the development of depression, and depression in patients may result in the development of Parkinson's disease as they mature. Depression is a non-motor condition that leads to motor symptoms, such as Parkinson's disease. PD Patients are currently utilizing a variety of other therapies like utilizing nutritional supplements, herbal remedies, vitamins, and massage. When a patient's functional ability is impaired, drug treatment is usually initiated according to the individual's condition and the severity of signs and symptoms. The current marketed anti-Parkinson drugs, has low brain distribution and failing to repair dopaminergic neurons or delaying the progression of the disease these negative effects were unavoidable. To overcome these disadvantages, this review considers the inclusion of drugs used in Parkinson's disease, focusing on strategies to reuse existing compounds to speed up drug development, their capacity to traverse the BBB, and drug dispersion in the brain. We look at cellular therapies and repurposed drugs. We also investigate the mechanisms, effectiveness, as well as safety of several new medications that are being repositioned for Parkinson's disease pharmacotherapy. In this study, we focus on global trends in Parkinson's disease research. We hope to raise awareness about the present state of major factors for disability worldwide, including yearly prevalence's from international and national statistics. The pathophysiology of Parkinsonism and also analyze existing therapies for Parkinson's disease, moreover new and innovative drug therapies, and to assess the prospects for disease modification.

Ovulation is triggered by a cyclical modulation of gonadotropes into a hyperexcitable state.

Gonadotropes in the anterior pituitary gland are essential for fertility and provide a functional link between the brain and the gonads. To trigger ovulation, gonadotrope cells release massive amounts of luteinizing hormone (LH). The mechanism underlying this remains unclear. Here, we utilize a mouse model expressing a genetically encoded Ca2+ indicator exclusively in gonadotropes to dissect this mechanism in intact pituitaries. We demonstrate that female gonadotropes exclusively exhibit a state of hyperexcitability during the LH surge, resulting in spontaneous [Ca2+]i transients in these cells, which persist in the absence of any in vivo hormonal signals. L-type Ca2+ channels and transient receptor potential channel A1 (TRPA1) together with intracellular reactive oxygen species (ROS) levels ensure this state of hyperexcitability. Consistent with this, virus-assisted triple knockout of Trpa1 and L-type Ca2+ subunits in gonadotropes leads to vaginal closure in cycling females. Our data provide insight into molecular mechanisms required for ovulation and reproductive success in mammals.

Bitter taste cells in the ventricular walls of the murine brain regulate glucose homeostasis.

The median eminence (ME) is a circumventricular organ at the base of the brain that controls body homeostasis. Tanycytes are its specialized glial cells that constitute the ventricular walls and regulate different physiological states, however individual signaling pathways in these cells are incompletely understood. Here, we identify a functional tanycyte subpopulation that expresses key taste transduction genes including bitter taste receptors, the G protein gustducin and the gustatory ion channel TRPM5 (M5). M5 tanycytes have access to blood-borne cues via processes extended towards diaphragmed endothelial fenestrations in the ME and mediate bidirectional communication between the cerebrospinal fluid and blood. This subpopulation responds to metabolic signals including leptin and other hormonal cues and is transcriptionally reprogrammed upon fasting. Acute M5 tanycyte activation induces insulin secretion and acute diphtheria toxin-mediated M5 tanycyte depletion results in impaired glucose tolerance in diet-induced obese mice. We provide a cellular and molecular framework that defines how bitter taste cells in the ME integrate chemosensation with metabolism.

Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism in mice.

Inter-organ communication is a major hallmark of health and is often orchestrated by hormones released by the anterior pituitary gland. Pituitary gonadotropes secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to regulate gonadal function and control fertility. Whether FSH and LH also act on organs other than the gonads is debated. Here, we find that gonadotrope depletion in adult female mice triggers profound hypogonadism, obesity, glucose intolerance, fatty liver, and bone loss. The absence of sex steroids precipitates these phenotypes, with the notable exception of fatty liver, which results from ovary-independent actions of FSH. We uncover paracrine FSH action on pituitary corticotropes as a mechanism to restrain the production of corticosterone and prevent hepatic steatosis. Our data demonstrate that functional communication of two distinct hormone-secreting cell populations in the pituitary regulates hepatic lipid metabolism.

Liver-Derived S100A6 Propels ß-Cell Dysfunction in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is an independent predictor of systemic insulin resistance and type 2 diabetes mellitus (T2DM). However, converse correlates between excess liver fat content and ß-cell function remain equivocal. Specifically, how the accumulation of liver fat consequent to the enhanced de novo lipogenesis (DNL) leads to pancreatic ß-cell failure and eventually to T2DM is elusive. Here, we have identified that low-molecular-weight calcium-binding protein S100A6, or calcyclin, inhibits glucose-stimulated insulin secretion (GSIS) from ß cells through activation of the receptor for the advanced glycation end products and diminution of mitochondrial respiration. Serum S100A6 level is elevated both in human patients with NAFLD and in a high-fat diet-induced mouse model of NAFLD. Although serum S100A6 levels are negatively associated with ß-cell insulin secretory capacity in human patients, depletion of hepatic S100A6 improves GSIS and glycemia in mice, suggesting that S100A6 contributes to the pathophysiology of diabetes in NAFLD. Moreover, transcriptional induction of hepatic S100A6 is driven by the potent regulator of DNL, carbohydrate response element-binding protein (ChREBP), and ectopic expression of ChREBP in the liver suppresses GSIS in a S100A6-sensitive manner. Together, these data suggest elevated serum levels of S100A6 may serve as a biomarker in identifying patients with NAFLD with a heightened risk of developing ß-cell dysfunction. Overall, our data implicate S100A6 as, to our knowledge, a hitherto unknown hepatokine to be activated by ChREBP and that participates in the hepato-pancreatic communication to impair insulin secretion and drive the development of T2DM in NAFLD.

Two-Step Visible Light Photocatalytic Dye Degradation Phenomena in Ag2O-Impregnated ZnO Nanorods via Growth of Metallic Ag and Formation of ZnO/Ag0/Ag2O Heterojunction Structures.

Visible light photocatalytic activity follows the single-slope pseudo-first-order reaction kinetics in pristine ZnO nanorods, while for pure Ag2O, a two-slope paradigm is pursued with a higher slope at a later period. For the Ag2O-impregnated ZnO heterostructured nanorod photocatalyst, the two-step photocatalysis phenomena proceed with dye degradation rate constants emerging higher than those of individual ZnO and Ag2O, at both time zones. Improved performance of ZnO/Ag2O heterostructures arises initially from the reduced e-/h+ recombination rate by the synergistic effect between ZnO and Ag2O. At a later phase, metallic Ag is produced, which traps the valence electrons of Ag2O nanoparticles and advances the e-/h+ separation across the ZnO/Ag0/Ag2O heterojunction structures, rendering them promptly accessible for dye degradation. At an increased Ag2O loading, the photodegradation rate constants boost up in both time zones, and the corresponding crossover time (tC) between the two phases steadily diminishes, leading toward a unique photocatalytic phenomenon that prevails with a superior rate constant. The optimized ZAO25 heterostructure photocatalyst demonstrates ∼96.24% photodegradation of methylene blue (MB) dye within 30 min of visible light exposure, and its degradation rate constant is ∼0.24848 min-1, which is ∼26.75 times superior than that of pristine ZnO samples. The metal-induced biphasic photocatalysis phenomena have never been reported earlier.

Ex Vivo Dual-Hit Method for Inflammasome Activation in Liver.

Activation of the inflammasome in hepatocytes and the liver-resident macrophages is associated with drug-induced hepatotoxicity and a plethora of metabolic diseases including nonalcoholic steatohepatitis (NASH). Initiation of this innate immune response requires two concomitant signals resulting in the formation of a molecular assembly that post-transcriptionally maturates a specific set of cytokines. While signal 1 results from the engagement and activation of pattern recognition receptors, signal 2 can be induced by diverse stimuli including adenosine triphosphate (ATP). Among various modules, NOD-like receptor 3 (NLRP3) inflammasome activation followed by caspase-1-dependent proIL-1ß maturation has been observed in both preclinical models and NASH patients suggesting the crucial importance of inflammasome activation in NAFLD progression. The protocol reported here depicts an ex vivo method for investigating the role of inflammasome activation in macrophages and its impact on hepatocytes. We first described a rapid protocol for the isolation of primary Kupffer cells (KC) and hepatocytes from the murine liver. Next, to investigate the crosstalks between KCs and hepatocytes in the context of inflammasome activation, isolated KCs were activated with lipopolysaccharide (LPS), alone or in tandem with ATP, which resulted in inflammasome activation in KCs evident by abundant IL-1ß secretion. Isolated primary hepatocytes were treated with conditioned medium (CM) from activated KCs to investigate the effect of inflammasome activation by various readouts. Moreover, this model also enabled us to investigate the role of specific cytokines by neutralizing them in the CM of inflammasome-activated KC. This precise ex vivo method provides a comprehensive protocol for investigating hepatocellular inflammasome activation.

Phytochemical profiling of Balarista formulation by GC-MS analysis.

GC-MS analysis of different fractions of in-house Balarista formulation (IBF) and marketed Balarista formulations (M1, M2, M3 and M4) confirmed the presence of various active metabolites. The database of National Institute of Standards and Technology (NIST) library was used to identify these compounds. This study revealed the presence of benzoic acid as a predominant compound in n-hexane fraction of M3 (94.69%), M2 (61.99%) and M4 (56.67%); ethyl acetate fraction of M2 (40.68%); methanol fraction of M2 (49.10%) and M3 (24.02%) formulations. Hexan-2-ol (72.49%); 3,3-Bis(4-hydroxy-3-methylphenyl)-1H-indol-2-one (71.40%); 5-(Hydroxymethyl)furan-2-carbaldehyde (64.52%); Propan-2-ol (57.34%); 1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octane (52.35%); (2 R,3S,4S,5R,6R)-2,3,4,5,6,7-Hexahydroxyheptanal (26.47%) are the other major compounds. Identification of benzoic acid in marketed formulations indicates indiscriminate use of sodium benzoate, which was determined as benzoic acid equivalents. Detection of benzoic acid at high concentration may affect the therapeutic efficacy of these formulations.

Outcome of Sublingual Immunotherapy in Allergic Rhinitis.

Allergic rhinitis (AR) is one of the most common types of allergy worldwide. It has significant negative impact on the quality of life (QOL). One of the available causal treatments of AR is allergen specific immunotherapy which remains effective even after the end of treatment course, unlike symptomatic drugs. AR patients aged above five years, allergic to unavoidable allergen like house dust, mite etc., and refractory to maximal pharmacotherapy were included in present study. Patients allergic to avoidable allergen, taking beta-blocker medication, having other immunological disease, and who were pregnant, breast-feeding or lost to follow up, were excluded from the study. All patients included in the study underwent sublingual immunotherapy (SLIT). The impact of treatment is measured by calculating the difference between SNOT-20 score before and after treatment (which is 6 months interval). Total 30 patients were studied. Paired-t test calculated value of cumulative score and nasal symptom score are 7.853 and 6.85 respectively. Both are greater than table value of 2.46. So paired-t test shows that SLIT is very much effective in treatment of AR. The present study re-establish the fact that SLIT not only reduces AR symptoms, it also improves the QOL. It has very good patient compliance with minimal side effects.

A nexus of miR-1271, PAX4 and ALK/RYK influences the cytoskeletal architectures in Alzheimer's Disease and Type 2 Diabetes.

Alzheimer's Disease (AD) and Type 2 Diabetes (T2D) share a common hallmark of insulin resistance. Reportedly, two non-canonical Receptor Tyrosine Kinases (RTKs), ALK and RYK, both targets of the same micro RNA miR-1271, exhibit significant and consistent functional down-regulation in post-mortem AD and T2D tissues. Incidentally, both have Grb2 as a common downstream adapter and NOX4 as a common ROS producing factor. Here we show that Grb2 and NOX4 play critical roles in reducing the severity of both the diseases. The study demonstrates that the abundance of Grb2 in degenerative conditions, in conjunction with NOX4, reverse cytoskeletal degradation by counterbalancing the network of small GTPases. PAX4, a transcription factor for both Grb2 and NOX4, emerges as the key link between the common pathways of AD and T2D. Down-regulation of both ALK and RYK through miR-1271, elevates the PAX4 level by reducing its suppressor ARX via Wnt/ß-Catenin signaling. For the first time, this study brings together RTKs beyond Insulin Receptor (IR) family, transcription factor PAX4 and both AD and T2D pathologies on a common regulatory platform.

Prion-derived tetrapeptide stabilizes thermolabile insulin via conformational trapping.

Unfolding followed by fibrillation of insulin even in the presence of various excipients grappled with restricted clinical application. Thus, there is an unmet need for better thermostable, nontoxic molecules to preserve bioactive insulin under varying physiochemical perturbations. In search of cross-amyloid inhibitors, prion-derived tetrapeptide library screening reveals a consensus V(X)YR motif for potential inhibition of insulin fibrillation. A tetrapeptide VYYR, isosequential to the ß2-strand of prion, effectively suppresses heat- and storage-induced insulin fibrillation and maintains insulin in a thermostable bioactive form conferring adequate glycemic control in mouse models of diabetes and impedes insulin amyloidoma formation. Besides elucidating the critical insulin-IS1 interaction (R4 of IS1 to the N24 insulin B-chain) by nuclear magnetic resonance spectroscopy, we further demonstrated non-canonical dimer-mediated conformational trapping mechanism for insulin stabilization. In this study, structural characterization and preclinical validation introduce a class of tetrapeptide toward developing thermostable therapeutically relevant insulin formulations.

Proteasome dysfunction under compromised redox metabolism dictates liver injury in NASH through ASK1/PPARγ binodal complementary modules.

Incidence of hepatotoxicity following acute drug-induced proteasomal inhibition and development of chronic proteasome dysfunction in obesity and insulin resistance underscores the crucial importance of hepatic protein homeostasis albeit with an elusive molecular basis and therapeutic opportunities. Apart from lipotoxicity and endoplasmic reticulum (ER) stress, herein we report that hepatocytes are highly susceptible to proteasome-associated metabolic stress attune to altered redox homeostasis. Bortezomib-induced proteasomal inhibition caused severe hepatocellular injury independent of ER stress via proapoptotic Apoptosis Signal-regulating Kinase 1 (ASK1)- c-Jun N-terminal kinase (JNK1)- p38 signaling concomitant with inadequate peroxisome proliferator-activated receptor γ (PPARγ)- Nuclear factor erythroid 2-related factor 2 (Nrf2) -driven antioxidant response. Although inhibition of ASK1 rescued acute hepatotoxicity, hepatic depletion of PPARγ or its physiological activator pigment epithelium-derived factor (PEDF) further aggravated liver injury even under ASK1 inhibition, emphasizing that endogenous PPARγ driven antioxidant activity serves as a prerequisite for the favorable therapeutic outcome of ASK1 inhibition. Consequently, ASK1 inhibitor selonsertib and PPARγ agonist pioglitazone in pharmacological synergism ameliorated bortezomib-induced hepatotoxicity and significantly prolonged survival duration in mice. Moreover, we showed that proteasome dysfunction is associated with ASK1 activation and insufficient PPARγ/Nrf2-driven antioxidative response in a subset of human nonalcoholic steatohepatitis (NASH) patients and the preclinical NASH model. The latter remains highly responsive to the drug combination marked by revamped proteasomal activity and alleviated hallmarks of NASH such as steatosis, fibrosis, and hepatocellular death. We thus uncovered a pharmacologically amenable interdependent binodal molecular circuit underlying hepatic proteasomal dysfunction and associated oxidative injury.

Reduced Graphene Oxide-Laminated One-Dimensional TiO2-Bronze Nanowire Composite: An Efficient Photoanode Material for Dye-Sensitized Solar Cells.

A facile one-step hydrothermal method was developed to prepare reduced graphene oxide-laminated TiO2-bronze (TiO2-B) nanowire composites (TNWG), which contain two-dimensional graphene oxide nanosheets and TiO2-B nanowires. In the hydrothermal process, the functional groups of graphene oxide were reduced significantly. Dye-sensitized solar cells (DSSCs) were fabricated using TNWG as the photoanode material. The effects of different reduced graphene oxide contents in TNWG on the energy conversion efficiency of the dye-sensitized solar cells were investigated using J-V and incident photon-to-current conversion efficiency characteristics. DSSCs based on a TNWG hybrid photoanode with a reduced graphene oxide content of 8 wt % demonstrated an overall light-to-electricity conversion efficiency of 4.95%, accompanied by a short-circuit current density of 10.41 mA cm-2, an open-circuit voltage of 0.71 V, and a fill factor of 67%, which were much higher than those of DSSC made with a pure TiO2-B NW-based photoanode. The overall improvement in photovoltaic performance could be associated to the intense visible light absorption and enhanced dye adsorption because of the increased surface area of the composite, together with faster electron transport due to reduced carrier recombination.

Subcutaneous amyloidoma models for screening potential anti-fibrillating agents in vivo.

Here, we describe a robust protocol using mouse models to screen potential insulin-stabilizers and insulin moieties. We have generated a mouse model of amyloidoma, found in diabetic patients undergoing insulin therapy. This model can be used to screen potential insulin stabilizers and insulin moieties to prevent amyloidoma formation. This protocol can further be used for the preclinical validation of therapeutically relevant insulin stabilizers and formulations. The protocol highlights all the critical steps for generating amyloidoma in a preclinical model. For complete details on the use and execution of this profile, please refer to Mukherjee et al. (2021).

Autogenic single p/n-junction solar cells from black-Si nano-grass structures of p-to-n type self-converted electronic configuration.

Photovoltaic performance of solar cells automatically improves when the absorber layer itself simultaneously acts as the anti-reflection nanostructure with an enhanced active absorber area on the front surface. Combined physical and chemical etching of p-c-Si wafers by (Ar + H2) plasma in inductively coupled low-pressure plasma CVD produces various nanostructures with subsequent minimization of reflectance. At a reduced temperature, the rate constant of thermal diffusion of atomic-H in the Si-network becomes smaller, leading to enhanced chemical etching reactions that further increase at an elevated RF power. Regrowth of the SiHn precursors produced by etching and subsequent hydrogenation in the plasma develops a high density of elongated nano-grass structures, which further align with sharp tips via Ar+ ion bombardment and elimination of loosely bound amorphous over-layers, on application of negative dc substrate bias during real-time etching and regrowth. A significantly reduced reflectance (∼0.5%) via coherent light trapping within the uniformly distributed vertically aligned nano-grass surfaces evolves truly black-silicon (b-Si) nanostructures, which further self-convert from the p-type to n-type electronic configuration via etching-mediated modification of B-H bonds from BH1 to BH2 and/or BH3 states, producing autogenic p/n junctions. Using (Ar + H2) plasma etched b-Si nano-grass structures at low temperature (∼200 °C), one-step fabrication of autogenic single p/n-junction proof-of-concept solar cells is accomplished. There is plenty of room for further progress in device performance.

Biocompatible implant mimicking cartilage: A new horizon for reconstructive facial field.

Cartilage is avascular with limited to no regenerative capacity, so its loss could be a challenge for reconstructive surgery. Current treatment options for damaged cartilage are also limited. In this aspect there is a tremendous need to develop an ideal cartilage-mimicking biomaterial that could repair maxillofacial defects. Considering this fact in this study we have prepared twelve silicone-based materials (using Silicone 40, 60, and 80) reinforced with hydroxyapatite, tri-calcium phosphate, and titanium dioxide which itself has proven their efficacy in several studies and able to complement the shortcomings of using silicones. Among the mechanical properties (Young's modulus, tensile strength, percent elongation, and hardness), hardness of Silicone-40 showed similarities with goat ear (P > .05). Silicone peaks have been detected in FTIR. Both AFM morphology and SEM images of the samples confirmed more roughed surfaces. All the materials were nonhemolytic in hemocompatibility tests, but among the twelve materials S2, S3, S5, and S6 showed the least hemolysis. For all tested bacterial strains, adherence was lower on each material than that grown on the plain industrial silicone material which was used as a positive control. S2, S3, S5, and S6 samples were selected as the best based on mechanical characterizations, surface characterizations, in vitro hemocompatibility tests and bacterial adherence activity. So, outcomes of this present study would be promising when developing ideal cartilage-mimicking biocomposites and their emerging applications to treat maxillofacial defects due to cartilage damage.

Resveratrol as a nontoxic excipient stabilizes insulin in a bioactive hexameric form.

Insulin aggregation is the leading cause of considerable reduction in the amount of active drug molecules in liquid formulations manufactured for diabetes management. Phenolic compounds, such as phenol and m-cresol, are routinely used to stabilize insulin in a hexameric form during its commercial preparation. However, long term usage of commercial insulin results in various adverse secondary responses, for which toxicity of the phenolic excipients is primarily responsible. In this study we aimed to find out a nontoxic insulin stabilizer. To that end, we have selected resveratrol, a natural polyphenol, as a prospective nontoxic insulin stabilizer because of its structural similarity with commercially used phenolic compounds. Atomic force microscopy visualization of resveratrol-treated human insulin revealed that resveratrol has a unique ability to arrest hINS in a soluble oligomeric form having discrete spherical morphology. Most importantly, resveratrol-treated insulin is nontoxic for HepG2 cells and it effectively maintains low blood glucose in a mouse model. Cryo-electron microscopy revealed 3D morphology of resveratrol-stabilized insulin that strikingly resembles crystal structures of insulin hexamer formulated with m-cresol. Significantly, we found that, in a condition inductive to amyloid fibrillation at physiological pH, resveratrol is capable of stabilizing insulin more efficiently than m-cresol. Thus, this study describes resveratrol as an effective nontoxic natural molecule that can be used for stabilizing insulin in a bioactive oligomeric form during its commercial formulation.

Characterization of Nanoscale Organization of F-Actin in Morphologically Distinct Dendritic Spines In Vitro Using Supervised Learning.

The cytoarchitecture of a neuron is very important in defining morphology and ultrastructure. Although there is a wealth of information on the molecular components that make and regulate these ultrastructures, there is a dearth of understanding of how these changes occur or how they affect neurons in health and disease. Recent advances in nanoscale imaging which resolve cellular structures at the scale of tens of nanometers below the limit of diffraction enable us to understand these structures in fine detail. However, automated analysis of these images is still in its infancy. Towards this goal, attempts have been made to automate the detection and analysis of the cytoskeletal organization of microtubules. To date, evaluation of the nanoscale organization of filamentous actin (F-actin) in neuronal compartments remains challenging. Here, we present an objective paradigm for analysis which adopts supervised learning of nanoscale images of F-actin network in excitatory synapses, obtained by single molecule based super-resolution light microscopy. We have used the proposed analysis to understand the heterogeneity in the organization of F-actin in dendritic spines of primary neuronal cultures from rodents. Our results were validated using ultrastructural data obtained from platinum replica electron microscopy (PREM). The automated analysis approach was used to differentiate the heterogeneity in the nanoscale organization of F-actin in primary neuronal cultures from wild-type (WT) and a transgenic mouse model of Alzheimer's disease (APPSwe/PS1ΔE9).