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.

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.

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.

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.

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.

Aß mediates F-actin disassembly in dendritic spines leading to cognitive deficits in Alzheimer's disease.

Dendritic spine loss is recognized as an early feature of Alzheimer's disease (AD), but the underlying mechanisms are poorly understood. Dendritic spine structure is defined by filamentous actin (F-actin) and we observed depolymerization of synaptosomal F-actin accompanied by increased globular-actin (G-actin) at as early as 1 month of age in a mouse model of AD (APPswe/PS1ΔE9, male mice). This led to recall deficit after contextual fear conditioning (cFC) at 2 months of age in APPswe/PS1ΔE9 male mice, which could be reversed by the actin-polymerizing agent jasplakinolide. Further, the F-actin-depolymerizing agent latrunculin induced recall deficit after cFC in WT mice, indicating the importance of maintaining F-/G-actin equilibrium for optimal behavioral response. Using direct stochastic optical reconstruction microscopy (dSTORM), we show that F-actin depolymerization in spines leads to a breakdown of the nano-organization of outwardly radiating F-actin rods in cortical neurons from APPswe/PS1ΔE9 mice. Our results demonstrate that synaptic dysfunction seen as F-actin disassembly occurs very early, before onset of pathological hallmarks in AD mice, and contributes to behavioral dysfunction, indicating that depolymerization of F-actin is causal and not consequent to decreased spine density. Further, we observed decreased synaptosomal F-actin levels in postmortem brain from mild cognitive impairment and AD patients compared with subjects with normal cognition. F-actin decrease correlated inversely with increasing AD pathology (Braak score, Aß load, and tangle density) and directly with performance in episodic and working memory tasks, suggesting its role in human disease pathogenesis and progression.SIGNIFICANCE STATEMENT Synaptic dysfunction underlies cognitive deficits in Alzheimer's disease (AD). The cytoskeletal protein actin plays a critical role in maintaining structure and function of synapses. Using cultured neurons and an AD mouse model, we show for the first time that filamentous actin (F-actin) is lost selectively from synapses early in the disease process, long before the onset of classical AD pathology. We also demonstrate that loss of synaptic F-actin contributes directly to memory deficits. Loss of synaptosomal F-actin in human postmortem tissue correlates directly with decreased performance in memory test and inversely with AD pathology. Our data highlight that synaptic cytoarchitectural changes occur early in AD and they may be targeted for the development of therapeutics.

Inflammasome activation in Kupffer cells confers a protective response in nonalcoholic steatohepatitis through pigment epithelium-derived factor expression.

Hepatocellular death or ballooning distinguishes the transition of simple steatosis to irreversible nonalcoholic steatohepatitis (NASH). However, the molecular mechanism of hepatocellular apoptosis in NASH is largely unclear, and discovery of endogenous mediators that could prevent or inhibit cell death is thereby critical in intercepting NASH progression. Here, we identified pigment epithelium-derived factor (PEDF), a secreted, moonlighting hepatokine as 1 hepatoprotective agent in mice with diet-induced NASH. Hepatic PEDF expression is induced by IL-1ß, which is derived from inflammasome activation in liver-resident Kupffer cells, an effect that is negatively regulated by TNF-α and predominantly secreted by monocyte-derived, recruited, hepatic macrophages. Mechanistically, reciprocal and opposing roles for IL-1ß and TNF-α in PEDF expression are mediated by differential activation of NF-κB. Although augmented TNF-α production leads to temporal reduction of PEDF expression in NASH, PEDF conversely abrogates TNF-α-mediated hepatocyte death by modulating the extrinsic apoptosis pathway. Thus, our study highlights PEDF as a functionally important hepatokine in NASH progression by linking inflammasome activation and hepatocellular death.-Adak, M., Das, D., Niyogi, S., Nagalakshmi, C., Ray, D., Chakrabarti, P. Inflammasome activation in Kupffer cells confers a protective response in nonalcoholic steatohepatitis through pigment epithelium-derived factor expression.

Development of optimum p-nc-Si window layers for nc-Si solar cells.

p-Type nc-Si (p-nc-Si) films have been optimized under low growth temperature (∼180 °C) and low power (∼30 W) parametric conditions in 13.56 MHz RF-PECVD. At elevated gas pressure (p), the growth rate enhances; however, the optical band gap reduces. At optimum p = 2.5 Torr, a p-nc-Si window-layer possessing high crystallinity, large grain size, high electrical conductivity, wide optical band gap and a preferred 〈220〉 crystallographic orientation of the nanocrystallites is obtained. Single p-i-n junction nc-Si solar cells in superstrate configuration have been realized with reasonably acceptable conversion efficiency, η ∼ 7.05%. The preferred 〈220〉 oriented (I〈220〉/I〈111〉 ∼ 1.68) highly crystalline (XC ∼ 86%) p-nc-Si window-layer minimizes the lattice mismatch at the p/i-junction, facilitates the growth of proper crystallinity in the i-nc-Si absorber layer from its incubation stage during its sequential growth over the window layer and ensures low recombination losses for conduction of charge carriers along the vertical direction at the p/i-interface. Further improvement in cell efficiency sensitively depends on proper optimization and future ungradation of the i-nc-Si absorber layer, and the single junction nc-Si cell could play a significant role as an integral part of premium all-Si tandem structure solar cells.

SYNTHESIS AND CYTOTOXIC EVALUATION OF SOME 2-{4-[(2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL] PHENOXY}-N-PHENYLACETAMIDE.

A series of 2-oxindole derivatives were synthesized and evaluated for cytotoxic activity against different human and murine cancer cell lines and cancer chemopreventive activity. Among the tested compounds VS-06, 08, 12 and 17 displayed cytotoxic activity in the range of 5.0 to 8.5 pM against human T-lymphocyte cells (CEM). Results showed that molecules with electron withdrawing substituent at 4 position of N-phenylacetamide group exhibited an increase in activity against the human tumor cell line CEM. The cancer chemo- preventive effect of VS-01 (IC50 = 451 nM) displayed equipotent activity in comparison to standard oleanolic acid (IC50 = 449 nM).

Effect of hydrogen in controlling the structural orientation of ZnO:Ga:H as transparent conducting oxide films suitable for applications in stacked layer devices.

Hydrogenation of the ZnO:Ga network has been chosen as a promising avenue to further upgrade the optoelectronic and structural properties of the films. With an optimum incorporation of hydrogen at a low substrate temperature (TS = 100 °C) in RF magnetron sputtering plasma, the ZnO:Ga:H film, with a large crystallite size (∼17 nm) and improved crystallinity along the optimally preferred c-axis orientation with respect to both the 〈100〉 (I〈002〉/I〈100〉 ∼ 74) and 〈103〉 (I〈002〉/I〈103〉 ∼ 10) directions, attains a high electrical conductivity (σ ∼ 1.5 × 10(3)) and ∼90% visible range optical transmission that yields a wide optical band gap of ∼3.78 eV. The dominant c-axis orientation of the ZnO crystals exhibits a distinct UV luminescence band at ∼340 nm that arises as a result of the typical exciton emission or near-band-edge emission, which occurs due to the recombination of photo-generated electrons and holes in the valence band or in traps near the valence band. Vacancies created by the out diffusion of oxygen from the network induces the growth along the 〈103〉 crystallographic orientation. With the introduction of an optimum amount of hydrogen into the network, the VO peak (OII) in the O 1s XPS spectrum significantly reduces in intensity while the Zn-OH peak (OIII) increases, indicating enhanced surface absorption of O species, which causes the improvement of c-axis orientation. The increase in the conductivity has been attributed to the centers assigned to isolated hydrogen atoms in the anti-bonding sites (ABO) or bond-centered sites of O-Zn bonds (BC), and Zn vacancies passivated by one or two hydrogen atoms. Hydrogen-induced dopant-like defects in the film and the associated large amount of tensile stress developed within the network has been correlated to the high conductivity and the wide band gap of the ZnO:Ga:H film due to the decreased repulsion between the O 2p and the Zn 4s bands and the Burstein-Moss effect as a consequence of the increased carrier concentration. Highly conducting and transparent c-axis oriented ZnO:Ga:H films grown by a device compatible process at a low TS are extremely useful for various stacked layer thin film devices, including solar cells.

Investigation of the vertical electrical transport in a-Si:H/nc-Si:H superlattice thin films.

Tuning the size of silicon nano-crystallites (Si-ncs) has been realized simply by controlling the thickness of the nc-Si:H sub-layer (tnc) in the a-Si:H/nc-Si:H superlattice thin films grown by low temperature plasma processing in PE-CVD. The vertical electrical transport phenomena accomplished in superlattice films have been investigated in order to identify their effective utilization in practical device configuration. The reduced size of the Si-ncs at thinner tnc and the associated band gap widening due to quantum confinement effects generates the Coulomb potential barrier at the a-Si/nc-Si interface which in turn obstructs the transport of charge carriers to the allowed energy states in Si-ncs, leading to the Poole-Frenkel tunneling as the prevailing charge transport mechanism in force. The advantages of the conduction process governed by the Poole-Frenkel mechanism are two-fold. The lower barrier height caused by the a-Si:H sub-layer in the superlattice than the silicon oxide sub-layer in conventional structures enhances the conduction current. Moreover, increasing trapped charges in the a-Si:H sub-layer can arbitrarily increase the current conduction. Accordingly, a-Si:H/nc-Si:H superlattice structures could provide superior electrical transport in stacked layer devices e.g., multi-junction all silicon solar cells.

Quantum size effects on the optical properties of nc-Si QDs embedded in an a-SiOx matrix synthesized by spontaneous plasma processing.

Quantum confinement effects on optical transitions in ensembles of nc-Si QDs in an a-SiOx matrix has become evident by simultaneously considering the dielectric function dispersions obtained by optical modeling with spectroscopic ellipsometry, the absorption edge, and the photoluminescence peak. Diminution of the peak amplitude in the ε2-spectra for reducing the diameter of nc-Si QDs could arise due to the disappearance of excitonic effects in the E1 transition, while the peak broadening indicates an amplification of disorder in Si QDs. An energy blue shift happens to take place in an analogous fashion for all the characteristic parameters, upon decreasing the size of the nc-Si QDs for diameters in the range 6.5 < d < 2.0 nm. The band gap widening with the reduction of QD size is well supported by the first-principles calculations based on quantum confinement, while studies on the Stokes shift in the optical gap from the PL data could provide an understanding of the imperfect passivation of the surface defects on tiny nc-Si QDs. Low dimensional nc-Si QDs (∼2 nm in diameter) assembled in a large density (∼2.3 × 10(12) cm(-2)) embedded in an a-SiOx matrix synthesized by spontaneous and low-temperature (300 °C) RF plasma processing, compatible to CMOS technology, are highly conducive for device applications. Systematic changes in composition and characteristics, including the thickness, of the individual sub-layers of the nc-Si QD thin films can be comprehensively pursued through a nondestructive process by ellipsometric simulation which could, thereby, enormously contribute to the precise optimization of the deposition parameters suitable for specific device fabrication e.g., all-silicon tandem solar cells and light emitting diodes, using silicon nanotechnology.

Unusual denaturation trajectory of bovine gamma globulin studied by fluorescence correlation spectroscopy.

Non-native and denatured states of proteins have received increasing attention because of their relevance to issues such as protein folding and stability. In this context, the pathway of polypeptide collapse and random coil formation in a denatured protein is a subject of much interest. Most proteins so far studied have shown monotonic expansion of their hydrodynamic radius (RH) in the presence of increasing concentration of chaotropes. We have studied GdnHCl-induced folding transitions and conformational states of a multi-domain protein, bovine gamma globulin, using fluorescence, circular dichroism and fluorescence correlation spectroscopy (FCS). FCS measurements showed that for gamma globulin, contrary to the observed trend, RH decreases with increasing GdnHCl concentration up to 3 M. At higher GdnHCl concentration, RH starts to increase but exhibits complicated behavior in the form of two sharp maxima at 4 M and 7 M. Further experiments suggest that the maximum at 4 M GdnHCl arises due to electrostatic interaction, whereas the one at 7 M GdnHCl corresponds to the usual expanded conformation due to denaturation. Beyond 7 M GdnHCl, RH decreases drastically and is shown to result from fragmentation of the protein caused by rupture of disulphide bonds by the high GdnHCl concentration. Our results demonstrate the capability of FCS in revealing intricate details of the unfolding trajectory that eludes conventional ensemble techniques such as fluorescence and CD.

Spectroscopic and microscopic studies of self-assembled nc-Si/a-SiC thin films grown by low pressure high density spontaneous plasma processing.

In view of suitable applications in the window layer of nc-Si p-i-n solar cells in superstrate configuration, the growth of nc-Si/a-SiC composite films was studied, considering the trade-off relation between individual characteristics of its a-SiC component to provide a wide optical-gap and electrically conducting nc-Si component to simultaneously retain enough crystalline linkages to facilitate proper crystallization to the i-nc-Si absorber-layer during its subsequent growth. Self-assembled nc-Si/a-SiC thin films were spontaneously grown by low-pressure planar inductively coupled plasma CVD, operating in electromagnetic mode, providing high atomic-H density. Spectroscopic simulations of ellipsometry and Raman data, and systematic chemical and structural analysis by XPS, TEM, SEM and AFM were performed. Corresponding to optimized inclusion of C essentially incorporated as Si-C bonds in the network, the optical-gap of the a-SiC component widened, void fraction including the incubation layer thickness reduced. While the bulk crystallinity decreased only marginally, Si-ncs diminished in size with narrower distribution and increased number density. With enhanced C-incorporation, formation of C-C bonds in abundance deteriorates the Si continuous bonding network and persuades growth of an amorphous dominated silicon-carbon heterostructure containing high-density tiny Si-ncs. Stimulated nanocrystallization identified in the Si-network, induced by a limited amount of carbon incorporation, makes the material most suitable for applications in nc-Si solar cells. The novelty of the present work is to enable spontaneous growth of self-assembled superior quality nc-Si/a-SiC thin films and simultaneous spectroscopic simulation-based optimization of properties for utilization in devices.

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.

Amlodipine Ocular Delivery Restores Ferning Patterns and Reduces Intensity of Glycosylated Peak of Carrageenan-Induced Tear Fluid: An In-Silico Flexible Docking with IL-ß1.

BACKGROUND: The tear ferning test can be an easy clinical procedure for the evaluation and characterization of the ocular tear film. OBJECTIVE: The objective of this study was to examine the restoration of tear ferning patterns and reduction of glycosylation peak after amlodipine application in carrageenan-induced conjunctivitis. METHODS: At the rabbit's upper palpebral region, carrageenan was injected for cytokine-mediated conjunctivitis. Ferning pattern and glycosylation of the tear fluid were characterized using various instrumental analyses. The effect of amlodipine was also examined after ocular instillation and flexible docking studies. RESULTS: Optical microscopy showed a disrupted ferning of the tear collected from the inflamed eye. FTIR of the induced tear fluid exhibited peaks within 1000-1200 cm-1, which might be due to the protein glycosylation absent in the normal tear spectrogram. The glycosylation peak reduced significantly in the tear sample collected from the amlodipine-treated group. Corresponding energy dispersive analysis showed the presence of sulphur, indicating protein leakage from the lacrimal gland in the induced group. The disappearance of sulphur from the treated group indicated its remedial effect. The flexible docking studies revealed a stronger binding mode of amlodipine with Interleukin-1ß (IL-1ß). The reduction in the intensity of the glycosylated peak and the restoration offering are probably due to suppression of IL-1ß. CONCLUSION: This study may be helpful in obtaining primary information for drug discovery to be effective against IL-1ß and proving tear fluid as a novel diagnostic biomarker.

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.

Insulin and leptin oscillations license food-entrained browning and metabolic flexibility.

Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.

Tunable photoluminescence from nc-Si/a-SiNx:H quantum dot thin films prepared by ICP-CVD.

Intense visible photoluminescence (PL) tunable within 1.66-2.47 eV, under UV 325 nm excitation, was obtained from nanocrystalline silicon quantum dots (∼5.72-1.67 nm in diameter) embedded in amorphous silicon-nitride matrix (nc-Si/a-SiN(x):H) prepared in RF-ICPCVD (13.56 MHz) at substrate temperatures between 400 to 150 °C. The dominant component of PL, having a narrow band width of ∼0.16-0.45 eV, originates from quasi-direct band-to-band recombination due to quantum confinement effect (QCE) in the nanocrystalline silicon quantum dots (nc-Si QDs) of appropriate size; however, the contribution of defects arose at lower substrate temperatures leading to asymmetric broadening. Intense atomic hydrogen flux in high-density inductively coupled plasmas (ICPs) provides a very high surface coverage, passivates well the nonradiative dangling bonds, and thereby favors the PL intensity. The average size of nc-Si QDs measured by HR-TEM appears consistent with similar estimates from Raman studies. The red shift of the Raman line and corresponding line broadening originates from the confinement of optical phonons within nc-Si QDs. Photoluminescence emerging from nc-Si/a-SiN(x):H quantum dots obtained from the low temperature and single-step plasma processing holds great promise for the fabrication of light-emitting devices and flexible flat panel displays.

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.