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Aims: Design isoxazole bearing leads as dual inhibitors against Amyloid β and BACE-1 loop in protein fibrillation. Background: Protein fibrillation is one of the key reasons for several diseases, namely Alzheimer’s, Parkinson’s, and many others. One of the key strategies of preventing protein fibrillation is destabilizing the protein fibrils themselves or inhibiting the amyloid fibril-forming pathway in the initial stage. Introduction: Attempts have been taken to design newer leads to inhibit protein fibrillation by targeting the β-amyloidogenesis pathway in the brain. To exploit interfenestration between Amyloid β -42 protein and BACE-1 (β-site amyloid precursor protein cleaving enzyme) for amyloidogenesis, studies are undertaken to design dual inhibitors against the same. Method: In vitro binding interactions were found using docking, de novo ligand design, and MD simulation study. Results: Three compounds bearing an isoxazole heterocyclic nucleus were designed which could successfully bind to the hydrophobic raft and salt bridge residues Asp 23-Lys-26 of Amyloid β, destabilizing the growing fibril. Additionally, one of our candidate compounds exhibited force of interaction with Thr232 at the S3 pocket of BACE-1, interacted with key residue Asp228, Tyr71, and Thr72 of the β-hairpin flap and hydrogen bonding with Gly11 at loop 10s. Conclusion: Protein flexibility dynamics of the Aβ-42 protein revealed that there is a considerable conformational change of the same with or without ligand binding. The lower RMSF of the bound region and reprogramming residual contacts within the Aβ-42 protein suggested successful binding of the ligand with the protein, lowering the access for further β-β dimerization.

Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the catecholamine (CA) biosynthesis pathway, making TH a molecular target for controlling CA production, specifically dopamine. Dysregulation of dopamine is correlated with neurological diseases such as Parkinson's disease (PD) and post-traumatic stress disorder (PTSD), among others. Previously, we showed that a 49-nucleotide guanine (G)-rich sequence within the human TH promoter adopts two different sets of G-quadruplex (GQ) structures (5'GQ and 3'GQ), where the 5'GQ uses G-stretches I, II, IV, and VI in TH49, which enhances TH transcription, while the 3'GQ utilizes G-stretches II, IV, VI, and VII, which represses transcription. Herein, we demonstrated targeted switching of these GQs to their active state using rationally designed DNA GQ Clips (5'GQ and 3'GQ Clips) to modulate endogenous TH gene expression and dopamine production. As a translational approach, we synthesized a targeted nanoparticle delivery system to effectively deliver the 5'GQ Clip in vivo. We believe this strategy could potentially be an improved approach for controlling dopamine production in a multitude of neurological disorders, including PD.

The objective of the present study was formulation and evaluation of pulsatile release tablets of Atenolol. A tablet system consisting of cores which was coated with layers of swelling and rupturable coatings. Cores containing Atenolol as model drug were prepared by direct compression with appropriate ratios of lactose and microcrystalline cellulose and then coated sequentially with different ratios of an inner swelling layer containing HPMC and an outer rupturable layer of Ethyl Cellulose. The effect of level of swelling layer and rupturable coating was investigated. The different formulation press coated by using different weight ratios of Hydroxy Propyl Methyl Cellulose (HPMC) / Ethyl Cellulose (EC) / both HPMC and EC. The optimum result was achieved in formulation containing HPMC: EC weight ratios. The F3 batch achieved a highest burst release after the lag time which is applicable pulsatile drug delivery system of Atenolol.

Diagram depicting the strategy for fabricating DNA-based hydrogels impregnated by ultrathin 2D tungsten disulfide nanosheets relevant for biomedical applications.

Cerium-promoted silica supported copper chromite catalyst was synthesized from acid hydrolysis of sodium silicate by sol–gel method. The catalyst was characterized by Brunauer–Emmett–Teller (BET) method, field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), H2-temperature programmed reduction (H2-TPR), NH3-temperature programmed desorption (NH3-TPD) and pyridine adsorbed Fourier transform infrared spectroscopy (Py-FTIR). Among cerium doped catalysts, 5 wt% of Ce promoted copper chromite supported by 40 wt% of silica (SiCuCr40–Ce5) shows the largest BET surface area. XRD analysis of the reduced form of the catalyst shows both CeO2/Ce2O3 redox system and CuO/Cu2O/Cu redox system. Py-Fourier shows the maximum number of Lewis acid sites for SiCuCr40–Ce5 than others. The highest acetol selectivity with analytical reagent (AR) grade glycerol conversion is observed for SiCuCr40–Ce5 at 200 °C for 3 h in a batch reactor at atmospheric pressure. Cerium promotion lowers the reaction temperature with enhanced glycerol conversion and increased acetol selectivity. Though the above catalyst shows higher conversion for laboratory reagent (LR) grade glycerol but it reduces acetol selectivity. The addition of glucose into the LR grade glycerol further reduces glycerol conversion and decreases the acetol selectivity to zero. This may be due to the presence of iron as impurity in LR grade glycerol. XRD analysis of spent catalyst shows the absence of redox catalytic system and the pore volume reduces identified by BET analysis. Raman analysis of the spent catalyst shows graphite-like carbon deposition in the spent catalyst.

We report morphological regulation of NaCl (sodium chloride) crystals through the evaporative crystallisation process of microdroplets containing a cationic surfactant CTAB (cetyltrimethylammonium bromide). Various fascinating evaporative salt morphologies are observed using a different combination of salt (CNaCl) and surfactant (CCTAB) concentrations. Each observed morphology is carefully explained by interplaying physical phenomena, such as crystallisation, micellisation, evaporative dewetting, and surface adsorption. Salt morphologies are investigated for a low (CNaCl= 0.1 (M)), intermediate (CNaCl= 0.5 (M)) and a high (CNaCl= 2 (M)) concentrations, whereas, surfactant concentrations are varied four orders of magnitudes (from 0.0001 (M) to 0.1 (M)). Interestingly, we observe a threshold in CCTAB at 0.001 (M), beyond which the peripheral rings of dried deposits are found to comprise of CTAB for CNaCl = 0.1 (M), while the same is seen to be made up of NaCl for CNaCl = 2 (M). We have explained the morphological evolution by the process of competitive surface adsorption phenomenon between Cl^- and Br^- counter ions. Such a detailed study of saline droplet crystallisation in the presence of a cationic surfactant underpins the fundamental understanding of the crystallisation process. In addition, it may further impact application sectors where saline solution crystallisation has an important role, especially in the presence of additives.

Graphical abstract, The Mg-dechelatase enzyme encoded by the Stay-Green (SGR) gene catalyzes Mg2+ dechelation from chlorophyll a. This reaction is the first committed step of chlorophyll degradation pathway in plants and is thus indispensable for the process of leaf senescence. There is no structural information available for this or its related enzymes. This study aims to provide insights into the structure and reaction mechanism of the enzyme through biochemical and computational analysis of an SGR homolog from the Chloroflexi Anaerolineae (AbSGR-h). Recombinant AbSGR-h with its intact sequence and those with mutations were overexpressed in Escherichia coli and their Mg-dechelatase activity were compared. Two aspartates – D34 and D62 were found to be essential for catalysis, while R26, Y28, T29 and D114 were responsible for structural maintenance. Gel filtration analysis of the recombinant AbSGR-h indicates that it forms a homo-oligomer. The three-dimensional structure of AbSGR-h was predicted by a deep learning-based method, which was evaluated by protein structure quality evaluation programs while structural stability of wild-type and mutant forms were investigated through molecular dynamics simulations. Furthermore, in concordance with the results of enzyme assay, molecular docking concluded the significance of D34 in ligand interaction. By combining biochemical analysis and computational prediction, this study unveils the detailed structural characteristics of the enzyme, including the probable pocket of interaction and the residues of structural and functional importance. It also serves as a basis for further studies on Mg-dechelatase such as elucidation of its reaction mechanism or inhibitor screening.

The osteochondral lesions and osteoarthritis-related complications continue to be clinically relevant challenges to be addressed by the biomaterials community. Hydrogel-based scaffolds have been widely investigated to enhance osteochondral regeneration, but the inferior mechanical properties together with poor functional stability are the major constraints in their clinical translation. The development of osteochondral implants with natural tissue-mimicking mechanical properties remains largely unexplored. In this perspective, the present study demonstrates a strategy to develop a bilayer osteochondral implant with an elastically stiff composite (poly(vinylidene difluoride)-reinforced BaTiO

The alpha/beta-fold superfamily of hydrolases is rapidly becoming one of the largest groups of structurally related enzymes with diverse catalytic functions. In this superfamily of enzymes, esterase deserves special attention because of their wide distribution in biological systems and importance towards environmental and industrial applications. Among various esterases, phthalate hydrolases are the key alpha/beta enzymes involved in the metabolism of structurally diverse estrogenic phthalic acid esters, ubiquitously distributed synthetic chemicals, used as plasticizer in plastic manufacturing processes. Although they vary both at the sequence and functional levels, these hydrolases use a similar acid-base-nucleophile catalytic mechanism to catalyse reactions on structurally different substrates. The current review attempts to present insights on phthalate hydrolases, describing their sources, structural diversities, phylogenetic affiliations and catalytically different types or classes of enzymes, categorized as diesterase, monoesterase and diesterase-monoesterase, capable of hydrolysing phthalate diester, phthalate monoester and both respectively. Furthermore, available information on in silico analyses and site-directed mutagenesis studies revealing structure-function integrity and altered enzyme kinetics have been highlighted along with the possible scenario of their evolution at the molecular level.

Nanocomposite formulation is still in its evolving state. However due to its significant therapeutic applications it has grabbed the attention of many researchers. Isoflavonewhich is widely found in soy products have tremendous medicinal propertieswhen it interacts with nanoparticles can become a boon. Hence in this study, we are reporting the interaction properties/patterns of two ubiquitous flavones namelyGlycitein and Genistein forming a nanocomposite model with 12 different metals such as Gold, Silver, Palladium, Platinum, Ruthenium, Rhodium, Cadmium, Iron, Nickel, Zinc, Copper and Antimony based ontheir potency to form nanoparticles. To mimic the Nanocomposite, model the formulation was conducted in Avogadro Software for windows. Glycitein and Genistein create a possibility of selecting the most suitable -OH position that would serve as the binding site. On selection of the appropriate binding site the interaction amid two molecules of glycitein and genistein placed sidewise held together by above-mentioned metals also surrounded by the same metal on another vacant -OH position forming a close saturated structure subjected for interaction. Based on predominantly energy levels the least energy obtained model was Cadmium and the peak procured by Antimony making it least stable and unfavorable for the perceived result.

Synthesis of Cu–In–S (CIS) nanoparticles by hot injection method using a mixed solution of Cu(acac), In(acac) and DDT in solvents OAm and trioctylphosphine oxide (TOPO), was carried in nitrogen atmosphere. Phase and crystallographic structure evolution were evaluated by extracting samples at intermediate synthesis stages and was characterized by X-ray diffraction and transmission electron microscopy. Ex-situ observation of phases indicated the formation and growth of Cu2S at the earlier stages. With further increase in temperature, CIS formed with the diffusion of In3+ ion. Wurtzite CIS nanoparticles preferentially grew along a length (from ~42 to 62 nm) while the width nearly remained constant to about ~32 nm. The preferential growth took place along [0002] while the particle width was oriented along [10 1 ‾ 0], which resulted in nearly oval-shaped nanoparticles. FTIR spectra recorded at different stages of synthesis (50–310 °C) pointed towards the ligand exchange mechanism after the addition of sulfur source at (160 °C).

The ability of atomistic and coarse-grained models to discern between two polymers of very similar architecture is examined. To this end, polyether ether ketone (PEEK) and polyether ketone ketone (PEKK) are chosen. The difference in glass transition temperature and the similarity in compressive responses of the two polymers are captured by all-atom models. A coarse-graining scheme, with 6 beads per monomer and 3 types of beads, leads to a good approximation of the structure and packing of chains of PEEK and PEKK. The CG model reproduces differences in weakly rate-dependent properties such as $${T}_{\mathrm{g}}$$ T g . Comparison between strongly rate-dependent uniaxial stress–strain responses of these two polymers requires a knowledge of the scaling between physical strain rate in one to the effective rate in the other. The scaling can be approximately determined by comparing the variation of yield strength with strain rate, obtained from small-sized simulations. Graphic abstract

To describe clinical and multimodal imaging characteristics of punctate inner retinal toxoplasmosis (PIRT) as an atypical presentation of ocular toxoplasmosis (OT).Retrospective review of OT cases ...

Objective: Till date, a very few prospective studies have examined the association between serum homocysteine levels and the risk of stroke and stroke subtypes in Indian populations. Methods: A prospective, case - control study of Indian subjects 10–90 years of age was conducted using frozen serum samples from 103 participants in cardiovascular risk surveys collected from December 2017 to November 2018. By the end of 103, we identified 55 incidents of severe strokes, one control subject per case was selected by matching for sex, age, community, year of serum storage, and fasting status. Serum total homocysteine levels were measured by Cobas c-311. Results: Compared with control subjects, total (n_206), hemorrhagic (n_106), and ischemic (n_87) strokes had higher geometric mean values of total homocysteine and higher proportions of homocysteine −25.0 μ mol/L. Homocysteine was estimated after adjustment for body mass index, smoking, alcohol intake, hypertension, and other cardiovascular risk factors. The excess risk of total and ischemic strokes did not vary significantly according to sex, age, smoking status, or hypertensive status. Conclusion: High total homocysteine concentrations were associated with the increased risk of total stroke, more specifically ischemic stroke) Capsuloganglionic and frontoparietal infarct (8 each)., among Indian men and women.

Glucose-responsive insulin delivery systems have the potential to improve quality of life for individuals with diabetes by improving blood sugar control and limiting the risk of hypoglycemia. However, systems with desirable insulin release kinetics and high loading capacities have proven difficult to achieve. Here, we report the development of electrostatic complexes (ECs) comprised of insulin, a polycation, and glucose oxidase (GOx). Under normoglycemic physiological conditions, insulin carries a slight negative charge and forms a stable EC with the polycation. In hyperglycemia, the encapsulated glucose-sensing enzyme GOx converts glucose to gluconic acid and lowers the pH of the microenvironment, causing insulin to adopt a positive charge. Thus, the electrostatic interactions are disrupted, and insulin is released. Using a model polycation, we conducted molecular dynamics simulations to model these interactions, synthesized ECs with > 50% insulin loading capacity, and determined in vitro release kinetics. We further showed that a single dose of ECs can provide a glycemic profile in streptozotocin-induced diabetic mice that mimics healthy mice over a 9 h period with 2 glucose tolerance tests.

Environmentally benign hydrogen production via photochemical and photoelectrochemical processes by water splitting using carbon-based nanomaterials utilizes sunlight as the source of energy. Owing to their large surface area, pore volume, chemical and thermal stability, and favorable morphology, the carbon-based nanomaterials are quite effective in photocatalytic water splitting. The present review elucidates the photocatalytic nature of carbon materials such as graphene, graphene oxide, carbon nanotubes, graphitic carbon nitride, and fullerenes as they have the tendency to narrow the band gap, allocate electrons, and act as semiconductors, co-catalysts, photosensitizers, and support materials. The production methods, advantages as well as shortcomings of carbon-based materials and their applications in hydrogen production are critically discussed.

PURPOSE: The urinary bladder generates phasic contractions via action potentials generated in pre- and then postganglionic neurons. Whilst the frequency-dependence of postganglionic neurons to generate contractions has been quantified, the dynamic range of preganglionic neurons is less clear and if intramural ganglia exert frequency-dependent modulation of transmission between pre- and postganglionic neurons. The phosphodiesterase type 5 inhibitor sildenafil reduces neurotransmitter release from postganglionic fibres to detrusor smooth muscle and an additional question was if there was also a preganglionic action. This study aimed to compare the frequency range of bladder contractile activation by pre- and postganglionic stimulation in pig and rat bladders and if sildenafil exerted additional preganglionic actions.METHODS: An arterially-perfused ex vivo pig bladder preparation was used for preganglionic (pelvic nerve) and mixed pre-and postganglionic (direct bladder wall) stimulation at 36°C and postganglionic mediated contractions achieved by field-stimulation of in vitro isolated detrusor strips. With rats, pelvic nerve stimulation was carried out in vivo and postganglionic stimulation also with isolated detrusor strips.RESULTS: All contractions were abolished by 2% lignocaine indicating they are nerve-mediated. Stimulation targets were verified with hexamethonium that completely abolished pelvic nerve responses by had no effect on detrusor strips; responses to mixed bladder wall stimulation were partially reduced. The frequency-dependence of contractile activation was similar whether by pre- or postganglionic stimulation in both pigs and rats. Sildenafil reduced contractions to preganglionic stimulation significantly more than to postganglionic stimulation. Mixed pre- and postganglionic stimulation were reduced by an intermediate extent.CONCLUSION: Intramural ganglia offer no frequency-dependent modulation under the experimental conditions used here and the sildenafil data are consistent with multiple sites of action underlying generation of bladder contractions. A translational aspect of these findings is discussed in terms of setting stimulation parameters for neuromodulation protocols.

The soil and groundwater of Asanpara village (Bhagobangola I block) of Murshidabad district are contaminated with non-permissible limit of arsenic and other elements that co-exist with arsenic in various chemical compounds like arsenopyrite, ferrous arsenate, ferric arsenate, etc. Arsenic resistant bacteria (ARB) were isolated from arsenic contaminated soil of Asanpara and biochemically characterized. These bacteria were identified as Lysinibacillus sp. and Bacillus safensis by 16S rDNA sequencing and subsequent phylogenetic analysis. Isolated strains could grow in 76.98 mM and 88.53 mM of arsenite, and 560.88 mM and 721.13 mM of arsenate, respectively. ARB also show hypertolerance to other toxic metals like copper (Cu2+), cobalt (Co2+) and chromium (Cr3+). The level of arsenic and other heavy metal tolerance is unprecedented. Based on the inhibition of urease activity of isolated ARB by cadmium, the bacteria can be used to detect the presence of cadmium. These bacteria could biotransform arsenite into arsenate, which explains its uninhibited growth at very high arsenic concentration. The change in size of these bacteria depicted by scanning electron microscopy is a defence mechanism against arsenic stress Lysinibacillus sp. shows 32.33%, 31.29% and 31.20% bioremediation, whereas Bacillus safensis shows 37.54%, 35.26% and 35.24% bioremediation in the presence of 0.027 mM (2 ppm), 0.133 mM (10 ppm) and 0.667 mM (50 ppm) arsenic, respectively. Also, these bacteria could bioaccumulate or bioadsorb arsenic. The bioremediation potential of isolated ARB could be exploited for removal of arsenic from soil, groundwater and wastewater.

High purity zirconium oxy chloride synthesis method has been developed from zircon sand of Chatrapur beach placer deposit of IREL Odisha. Chemical method of purification is found to be suitable means of producing high purity zirconium oxy chloride with very low radioactivity. Complexing agent such as pentetic acid or diethylene triamine penta acetic acid is found to be a good chelating agent for thorium removal from the bulk solution. The process has a potential for scaling up to a technology for production of bio-inert ceramics such as dental orthopaedic implants, coatings on other metallic implants, porous bone scaffolds and bone cements.

Modern 21st-century toxicity testing makes use of omics technologies to address critical questions in toxicology and chemical management. Of interest are questions relating to chemical mechanisms of toxicity, differences in species sensitivity, and translation of molecular effects to observable apical endpoints. Our study addressed these questions by comparing apical outcomes and multiple omics responses in early-life stage exposure studies with Japanese quail (Coturnix japonica) and double-crested cormorant (Phalacrocorax auritus), representing a model and ecological species, respectively. Specifically, we investigated the dose-dependent response of apical outcomes as well as transcriptomics and metabolomics in the liver of each species exposed to chlorpyrifos, a widely used organophosphate pesticide. Our results revealed a clear pattern of dose-dependent disruption of gene expression and metabolic profiles in Japanese quail but not double-crested cormorant at similar chlorpyrifos exposure concentrations. The difference in sensitivity between species was likely due to higher metabolic transformation of chlorpyrifos in Japanese quail compared to double-crested cormorant. The most impacted biological pathways after chlorpyrifos exposure in Japanese quail included hepatic metabolism, oxidative stress, endocrine disruption (steroid and nonsteroid hormones), and metabolic disease (lipid and fatty acid metabolism). Importantly, we show consistent responses across biological scales, suggesting that significant disruption at the level of gene expression and metabolite profiles leads to observable apical responses at the organism level. Our study demonstrates the utility of evaluating effects at multiple biological levels of organization to understand how modern toxicity testing relates to outcomes of regulatory relevance, while also highlighting important, yet poorly understood, species differences in sensitivity to chemical exposure. Environ Toxicol Chem 2021;40:3019-3033. © 2021 SETAC.

Objective The aim of present study was to determine and compare the overall response rates, progression-free survival (PFS), overall survival (OS), and clinical toxicity of the combination of 177Lu-PSMA-617 radioligand therapy (PRLT) and abiraterone acetate (AA) versus 177Lu-PSMA-617 PRLT as monotherapy in metastatic castration-resistant prostate cancer (mCRPC) patients. Materials and methods The mCRPC patients who received at least one cycle of 177 Lu-PSMA-617 PRLT with or without AA therapy, were included and analyzed in the present study. The patients were divided into two major groups. Group 1 received only 177 Lu-PSMA PRLT and Group 2 received combined 177 Lu-PSMA PRLT + AA therapy. Therapeutic dose of 177 Lu-PSMA-617 PRLT was 4.4-5.55 GBq per patient per cycle administered at intervals of 10-12 weeks in both groups. The Group 2 patients additionally received a dose of 1000 mg of AA once daily and 5 mg of prednisone twice daily. Treatment response in two groups was evaluated under four broad categories (a) symptomatic, (b) biochemical (serum prostate-specific antigen level), (c) objective molecular imaging (68 Ga-PSMA-11 and 18 F-FDG PET/CT), and (d) objective anatomical imaging (computed tomography). For assessing treatment response, patients in two groups were categorized into responders (complete response [CR], partial response [PR], and stable disease [SD]) and nonresponders (progressive disease [PD]). The Kaplan-Meier product-limit method was used to calculate PFS and OS following first 177 Lu-PSMA PRLT in the two groups. Univariate analysis was used to compare the patients' characteristics in two groups using a χ2 or Fisher exact test. The Kaplan-Meier curves of PFS and OS between two groups were compared by using the log-rank test (p Results A total of 58 mCRPC patients (Group 1, 38 patients and Group 2, 20 patients) were included in this study analysis. The clinical and demographic characteristics of these patients (age, Gleason score, FDG avid disease, metastatic disease burden, and average number of 177 Lu-PSMA PRLT cycles) in two groups were compared and found to be similar (p > 0.05). Post-treatment, symptomatic, biochemical, molecular, and anatomic imaging responders were found in 22 patients (58%) and 17 patients (85%), 22 patients (58%) and 16 patients (80%), 19 patients (54%) and 14 patients (78%), and 19 patients (54%) and 14 patients (78%) in Group 1 and Group 2, respectively. The median PFS of 7 months and median OS of 8 months were documented in Group 1, whereas median PFS was not reached and median OS of 16 months registered in Group 2. Transient hematological toxicity of Grades 1 and 2 was found in total seven patients (five patients in Group 1 and two patients in Group 2). On comparison of the treatment outcome between two groups, significant p value was found for symptomatic responders (58% in Group 1 vs. 85% in Group 2), median PFS (7 months in Group 1 vs. not reached in Group 2), and median OS (8 months in Group 1 vs. 16 months in Group 2), with better outcome in Group 2 patients for these variables. Conclusion In the present study, the combination of 177 Lu-PSMA-617 PRLT and AA therapy showed significant improvement in mCRPC patients' symptomatic response, PFS, and OS as compared to 177 Lu-PSMA-617 PRLT monotherapy.

Silicon (Si), a bioactive metalloid is beneficial for plant growth and development. It also plays a key role in the amelioration of different abiotic and biotic stresses. Extensive studies have elucidated the morpho-physiological, biochemical and molecular background of Si-mediated stress tolerance in plants. However, the mechanism acquired by Si to enhance stress tolerance in plants is still unheeded. Present review summarized the prospective mechanisms of Si in acquisition of stress tolerance with emphasis on its interactions with secondary messengers. Silicon usually modulates the different gene expressions in plants under stress conditions rather than acting as a direct signal or secondary messengers. Silicon regulates the production and accumulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in plants under stress conditions. Furthermore, Si also activates the antioxidant defence system in plants; thereby, maintaining the cellular redox homeostasis and preventing the oxidative damage of cells. Silicon also up-regulates the synthesis of hydrogen sulfide (H2S) or acts synergistically with nitric oxide (NO), consequently conferring stress tolerance in plants. Overall, the review may provide a progressive understanding of the role of Si in conservation of the redox homeostasis in plants.

Maghemite/ZnO nanocomposites synthesized by a two step process were used for catalytic reduction of p-nitrophenol. Maghemite nanoparticles were synthesized by hydrothermal technique followed by deposition of ZnO on it via co-precipitation process. X-ray diffraction analysis suggested formation of Maghemite and ZnO with tetragonal and hexagonal close packed structure respectively whereas electron microscopy images indicated the formation of near spherical nanocomposites with a size range of 30–50 nm. Maghemite/ZnO calcined at 300 °C is investigated as heterogeneous catalyst for reduction of p-nitrophenol and its catalytic activity is compared with that of Maghemite and ZnO nanoparticles. The parameters responsible for reduction of p-nitrophenol over Maghemite/ZnO were scrutinized using Response Surface Methodologyand the predicted values of reduction efficiency were found to be in a good agreement with the experimental findings (R2 > 0.9). The highest achievable percentage of reduction of target molecular species was noted to be of 98.6%. Optimization study showed that maximum reduction efficiency was observed at optimum conditions: p-NP concentration = 0.2 mM, Maghemite/ZnO loading = 200 ppm, reaction time = 6 min. Maghemite/ZnO has shown noticeably higher catalytic activity than pure oxides which remained almost unaltered for five consecutive cycling suggesting possible commercial potential of the developed material.

In this work, graphene oxide nanoparticles are dispersed in different concentrations in a soyabean extracted natural ester-based oil-blend having mineral oil as secondary oil and the resulting nanofluids are tested for various dielectric and physio-thermal properties. The results show that with the addition of nanoparticles, the breakdown voltage of nanofluids increases up to 42% as compared to pure mineral oil, 17% as compared to pure ester oil and 15% as compared to the base oil-blend. Relative permittivity and dissipation factor parameters follow a similar trend as well. Thus, the prepared nanofluids can be used as alternative insulating oils in place of the conventional mineral oil in oil-filled transformers.

Background: Organochlorine pesticides (OCPs) exposure may induce an endocrine disruption which may lead to the risk of developing diabetes through alteration and disturbance of glucose metabolism, insulin resistance, and destruction of β-cells. The present study determines the recent trend of OCPs residue in blood samples and their association with the known risk factors responsible for developing the risk of diabetes among the North Indian population.Methods: Blood sample of 300 patients (100 each of normal glucose tolerance [NGT], prediabetes and newly detected diabetes mellitus [DM]) between the age group of 30 to 70 years were collected. OCPs residue in whole blood samples was analyzed by using gas chromatography equipped with a 63Ni selective electron capture detector.Results: Significantly higher levels of β-hexachlorocyclohexane (HCH), dieldrin, and p,p’-dichloro-diphenyl-dichloroethylene (DDE) were found in the prediabetes and newly detected DM groups as compared to NGT group. Insulin resistance showed to be significantly positive correlation with β-HCH and dieldrin. Also, fasting and postprandial glucose levels were significantly positively correlated with levels of β-HCH, dieldrin, and p,p’-DDE. Further, when OCPs level was adjusted for age and body mass index (BMI), it was found that β-HCH, dieldrin, and p,p’-DDE levels in blood increases the risk of diabetes by 2.70, 2.83, and 2.55 times respectively. Moreover, when we adjust OCPs level based on BMI categories (BMI 25 kg/m2); β-HCH and p,p’-DDE showed a significant risk of developing newly detected DM with BMI >25 and ≥23 and ≤25 kg/m2.Conclusion: The OCPs level present in the environment may be responsible for biological, metabolic, and endocrine disruptions within the human body which may increase the risk of developing newly detected DM. Hence, OCPs exposure can play a crucial role in the etiology of diabetes.

The 11 zinc finger (ZF) protein CTCF regulates topologically associating domain formation and transcription through selective binding to thousands of genomic sites. Here, we replaced endogenous CTCF in mouse embryonic stem cells with green-fluorescent-protein-tagged wild-type or mutant proteins lacking individual ZFs to identify additional determinants of CTCF positioning and function. While ZF1 and ZF8–ZF11 are not essential for cell survival, ZF8 deletion strikingly increases the DNA binding off-rate of mutant CTCF, resulting in reduced CTCF chromatin residence time. Loss of ZF8 results in widespread weakening of topologically associating domains, aberrant gene expression and increased genome-wide DNA methylation. Thus, important chromatin-templated processes rely on accurate CTCF chromatin residence time, which we propose depends on local sequence and chromatin context as well as global CTCF protein concentration.

A large population of patients is reported to suffer from urinary bladder-associated irreversible physiological disorders, rationalizing a continuous surge for structural and functional substitutes of urinary tissues, including ureters, bladder-wall, and urethra. The current gold standard for bladder reconstruction, an autologous gastrointestinal graft, is proven not to be an ideal substitute in the clinic. While addressing this unmet clinical need, a unique platform of antimicrobial polydimethyl siloxane-modified polyurethanes (TPU/PDMS) is designed and developed for its potential application as a urological implant. To the best of our knowledge, this study reports for the first time the successful integration of varying contents of PDMS within the molten polyurethane matrix using in situ crosslinking methodology. Thus, compatibilized binary blends possess clinically relevant viscoelastic properties to sustain high pressure, large distensions, and surgical manipulation. Furthermore, different chemical strategies are explored to covalently incorporate quaternized moieties, including 4-vinyl pyridine (4-VP), branched-polyethyleneimine (bPEI) as well as bPEI-grafted-(acrylic acid-co-vinylbenzyltriphenyl phosphonium chloride) (PAP), and counter urinary tract infections. The modified compositions, endowed with contact killing surfaces, reveal nearly three log reduction in bacterial growth in pathogenically infected artificial urine. Importantly, the antimicrobial TPU/PDMS blends support the uninhibited growth of mitochondrially viable murine fibroblasts, in a manner comparable to the medical-grade polyurethane. Collectively, the obtained results affirmed the newly developed polymers as promising biomaterials in reconstructive urology. STATEMENT OF SIGNIFICANCE: The clinical procedure for end-stage bladder disease remains replacement or augmentation of the bladder wall with a section of the patient's gastrointestinal tract. However, the absorptive and mucus-producing epithelium of intestinal segment is liable to short- and long-term complications. The dynamically crosslinked polydimethyl siloxane-based polyurethanes proposed herein, and the associated synthesis strategies to induce polycation grafted non-exhaustive contact-killing surfaces against uropathogents, have a significant clinical prospect in reconstructive urology. As an 'off-the-shelf' available alloplastic substitute, these blends offer the potential to circumvent the challenges associated with non-urinary autografts or scaffold based regenerative engineering and, thereby, shorten as well as simplify the surgical treatment. The targeted application has been conceived for a bladder patch to assist in various urinary diseases including, bladder carcinoma, refractory overactive bladder, interstitial cystitis, etc. However, given the ease of fabrication, moldability and the wide spectrum of mechanical properties that could be encompassed, these blends also present the possibility to be manifested into artificial ureteral or urethral conduits.

Hydrogen is the solution to all the problems associated with the energy crisis. Generating hydrogen from water splitting is one of the greener approaches, but it requires an efficient catalyst that is economical for the bulk production of hydrogen. The transition metal-aqua coordination complexes, which are otherwise inactive/unstable for electrochemical hydrogen evolution reaction (HER) activity, can efficiently be utilized for the same by attaching these metal-aqua species on a stable support. With a similar approach, we have synthesized and structurally characterized a two-dimensional polyoxometalate (POM)-copper complex hybrid that supports a copper(II)-aqua-bypyridine complex with a molecular formula of the overall system, [{CuII(2,2'-bpy)(H2O)2}][{CoIIWVI12O40}{CuII(2,2'-bpy)(H2O)}{CuII(2,2'-bpy)}]·2H2O (1). The bis(aqua)-mono(bipyridine) Cu(II)-complex fragment {CuII(2,2'-bpy)(H2O)2}2+, attached to the two-dimensional POM-Cu-complex support, acts as an active catalytic center that catalyzes the electrochemical HER. The electrochemical studies done for this work enabled us to understand the role of compound 1 as an electrocatalyst for the HER in near-neutral medium (pH 4.8), under buffered conditions (acetate buffer). Through detailed electrochemical experiments including controlled ones, we understand that compound 1 follows a proton-coupled electron transfer (PCET) pathway with one proton and one electron involvement in the HER. The overpotential required to achieve a current density of 1 mA/cm2 is found to be 520 mV with a Faradaic efficiency of 81%.

PURPOSE: Patients with triple negative breast cancer (TNBC) who do not achieve pathological complete response (pCR) following neoadjuvant chemotherapy have a high risk of recurrence and death. Molecular characterization may identify patients unlikely to achieve pCR. This neoadjuvant trial was conducted to determine the pCR rate with docetaxel and carboplatin, and to identify molecular alterations and/or immune gene signatures predicting pCR. EXPERIMENTAL DESIGN: Patients with clinical stages II/III TNBC received 6 cycles of docetaxel and carboplatin. The primary objective was to determine if neoadjuvant docetaxel and carboplatin would increase the pCR rate in TNBC compared to historical expectations. We performed whole exome sequencing (WES) and immune profiling on pre-treatment tumor samples to identify alterations that may predict pCR. Thirteen matching on-treatment samples were also analyzed to assess changes in molecular profiles. RESULTS: Fifty-eight of 127 (45.7%) patients achieved pCR. There was a non-significant trend towards higher mutation burden for patients with residual cancer burden (RCB) 0/I versus RCB II/III (median 80, versus 68 variants, p 0.88). TP53 was the most frequently mutated gene, observed in 85.7% of tumors. EGFR, RB1, RAD51AP2, SDK2, L1CAM, KPRP, PCDHA1, CACNA1S, CFAP58, COL22A1, and COL4A5 mutations were observed almost exclusively in pre-treatment samples from patients who achieved pCR. Seven mutations in PCDHA1 were observed in pre-treatment samples from patients who did not achieve pCR. Several immune gene signatures including IDO1, PD-L1, interferon gamma signaling, CTLA4, cytotoxicity, tumor inflammation signature, inflammatory chemokines, cytotoxic cells, lymphoid, PD-L2, exhausted CD8, Tregs, and immunoproteosome were upregulated in pre-treatment samples from patients who achieved pCR. CONCLUSIONS: Neoadjuvant docetaxel and carboplatin resulted in a pCR of 45.7%. WES and immune profiling differentiated patients with and without pCR. TRIAL REGISTRATION: Clinical trial information: NCT02124902, Registered 24 April 2014, & NCT02547987, Registered 10 September 2015.

RNA as an effector of biological functions often adopts secondary and tertiary structural folds. Plasmodium falciparum is a deadly human pathogen responsible for the devastating disease called malaria. In this study, we measured the differential accumulation of RNA secondary structures in coding and noncoding transcripts from the asexual developmental cycle in P. falciparum in human red blood cells. Our comprehensive analysis, combining high-throughput nuclease mapping of RNA structures by duplex RNA-seq, immunoaffinity purification and RNA analysis, collectively measured differentially base-paired RNA regions during the parasite development. Our mapping data not only aligned to a diverse pool of RNAs with known structures but also enabled us to identify new structural RNA regions in the malaria genome. On average, ~71% of the genes with secondary structures are found to be protein coding mRNAs. Mapping pattern of these base-paired RNAs corresponded to all parts of protein-coding mRNAs, including 5’ UTR, CDS and 3’ UTR. In addition to histone family genes which are known to form secondary structures in their mRNAs, transcripts from genes which are important for transcriptional and post-transcriptional control, such as unique plant-like transcription factor family, ApiAP2, DNA/RNA binding protein family, Alba, ribosomal proteins and eukaryotic initiation factors involved in translational control and the ones important for RBC invasion and cytoadherence also show strong accumulation of duplex RNA reads in various asexual stages. Intriguingly, our study determined a positive relationship between mRNA structural contents and translation efficiency in P. falciparum asexual blood stages, suggesting an essential role of RNA structural changes in malaria gene expression programs.

In this work, we have observed change in different physical properties and glucose sensing capability of Chitosan-Silica nanoparticle composite membranes (CSNCM) with pore diameter variation. For a particular mixture percentage of chitosan and SiNp dust, successful fabrication of deformation free, free-standing membrane formation was possible. Silica nanoparticles of three different sizes (NP1 ~ 100 nm, NP2 ~ 300 nm & NP3 ~ 500 nm) were prepared to produce CSNCM of corresponding pore sizes (CM1, CM2 and CM3 respectively). Hot NaOH etching was performed to induce surface pore in CSNCM matrix by dissolving Silica nanoparticles from the top layer. We have found that pore distribution, surface morphology, optical properties and dielectric properties are very much dependent on pore size of the membranes. For glucose sensing characterization, we have focussed on multi-parametric optical sensitivity of the membranes in presence of glucose molecules and found that, though all three membranes show response in one or more parameters, only CM2 membranes hold the capability to perform as a multi-parametric sensor in our optical sensing arrangement.

The discovery of small molecules that exhibit turn-on far-red or near-infrared (NIR) fluorescence upon DNA binding and understanding how they bind DNA are important for imaging and bioanalytical applications. Here we report the DNA-bound structure and the DNA binding mechanism of quinone cyanine dithiazole (QCy-DT), a recently reported AT-specific turn-on NIR fluorescent probe for double-stranded DNA. The nuclear magnetic resonance (NMR)-derived structure showed minor groove binding but no specific ligand-DNA interactions, consistent with an endothermic and entropy-driven binding mechanism deduced from isothermal titration calorimetry. Minor groove binding is typically fast because it minimally perturbs the DNA structure. However, QCy-DT exhibited unusually slow DNA binding. The cyanine-based probe is capable of cis-trans isomerization due to overlapping methine bridges, with 16 possible slowly interconverting cis/trans isomers. Using NMR, density functional theory, and free energy calculations, we show that the DNA-free and DNA-bound environments of QCy-DT prefer distinctly different isomers, indicating that the origin of the slow kinetics is a cis-trans isomerization and that the minor groove preferentially selects an otherwise unstable cis/trans isomer of QCy-DT. Flux analysis showed the conformational selection pathway to be the dominating DNA binding mechanism at low DNA concentrations, which switches to the induced fit pathway at high DNA concentrations. This report of cis/trans isomerization of a ligand, upon binding the DNA minor groove, expands the prevailing understanding of unique discriminatory powers of the minor groove and has an important bearing on using polymethine cyanine dyes to probe the kinetics of molecular interactions.

The performance of solid oxide fuel cells (SOFCs) can be degraded by “chromium poisoning” where thermally grown Cr2O3 on metallic surfaces forms volatile Cr-containing species that are redeposited on active regions of the cathode. This phenomenon is further exacerbated for porous metallic interconnects and metal-supported electrodes due to their large surface-to-volume ratios. In this study, electrophoretic deposition (EPD) of CuNi0.2Mn1.8O4 spinel powders on porous SUS430 metallic substrates using alternating current (AC) was explored. Two-step densification heat treatment was used to form a thin, uniform, protective spinel coating. The area-specific resistance (ASR) and weight gain were tracked during 100-h oxidation tests at 700°C in air. The results showed that, despite the considerable complexity of the sample shape, AC EPD was able to form a protective coating layer that significantly limited the growth rate of the thermally grown oxide (TGO) by reducing the kg value by a factor of 25.

In the present study, we carried out comprehensive transcriptional profiling of diverse genes under salinity (200 mM NaCl) at different time points, accompanied by certain biochemical alterations of the indica (IR-64 and Pokkali) and japonica (Nipponbare and M-202) rice. The higher susceptibility of Nipponbare and IR-64 was reflected by lower relative water content, chlorophyll loss, higher malondialdehyde content and accumulation of H2 O2 , and reduced nitrate reductase activity, compared to M-202 and Pokkali, where such changes were less pronounced. Enhanced levels of anthocyanins and reduced glutathione, together with elevated phenylalanine ammonia lyase activity, mainly conferred protection to Nipponbare and IR-64, while metabolites like phenolics, flavonoids, proline and polyamines were more induced in M-202 and Pokkali. Varietal differences in the expression pattern of diverse groups of genes to different durations (6, 24 and 48 h) of stress were striking. A gene showing early induction for a particular variety exhibited a delayed induction in another variety or a gradually decreased expression with treatment time. Pokkali was clearly identified as the salt-tolerant genotype among the test varieties based on increased antioxidant potential and enhanced expression of genes encoding for PAL, CHS and membrane transporters like SOS3, NHX-1 and HKT-1. The results presented in this work provide insight into the complex varying regulation patterns for different genes across the investigated rice varieties in providing salt tolerance and highlights distinct differences in expression patterns between susceptible and tolerant indica and japonica rice. This article is protected by copyright. All rights reserved.

ATRX is a tumor suppressor that has been associated with protection from DNA replication stress, purportedly through resolution of difficult-to-replicate G-quadruplex (G4) DNA structures. While several studies demonstrate that loss of ATRX sensitizes cells to chemical stabilizers of G4 structures, the molecular function of ATRX at G4 regions during replication remains unknown. Here, we demonstrate that ATRX associates with a number of the MCM replication complex subunits and that loss of ATRX leads to G4 structure accumulation at newly synthesized DNA. We show that both the helicase domain of ATRX and its H3.3 chaperone function are required to protect cells from G4-induced replicative stress. Furthermore, these activities are upstream of heterochromatin formation mediated by the histone methyltransferase, ESET, which is the critical molecular event that protects cells from G4-mediated stress. In support, tumors carrying mutations in either ATRX or ESET show increased mutation burden at G4-enriched DNA sequences. Overall, our study provides new insights into mechanisms by which ATRX promotes genome stability with important implications for understanding impacts of its loss on human disease., ATRX is a chromatin remodeling protein, which loss has been associated to replication stress, DNA damage, and DNA repair failures that drive genome instability. Here the authors reveal that ATRX protects genomic integrity at G4-containing regions by maintaining these regions in a closed heterochromatic state.

The glucose intolerance of diabetes aggravates atherosclerosis indirectly through its effect on lipids and endothelial function. The cardiovascular (CV) impact of this metabolic disturbance is seen in the worsening of atherosclerotic vascular disease predominantly manifest as progression of coronary and cerebrovascular disease. The microvascular changes induced by prolonged glucose intolerance lead to ultrastructural changes in the glomerular basement membrane and renal mesangium which alters intrarenal haemodynamics, which may become evident initially as proteinuria and later lead to a decline in glomerular filtration rate. As the kidney plays a central role in blood pressure control, these changes have far-reaching CV consequences in patients with diabetes.Despite this, glucose lowering has been shown to have only a modest impact on CV outcomes in diabetes. The new antidiabetic medications have been studied in clinical trials designed to assure safety as grounded in the FDA guidance of 2008. Whilst a direct comparison of results from these trials is not possible in view of heterogeneity in trial design, the individual CV outcome measures have broadly re-defined their role in terms of equivalence (non-inferiority) and/or benefit (superiority). The composite endpoint of CV death, non-fatal myocardial infarction and non-fatal stroke (major adverse cardiovascular events, MACE) may be perceived as surrogate markers for atherosclerotic cardiovascular disease (ASCVD). This has been universally accepted as the primary endpoint in these cardiovascular outcome trials (CVOTs) and has been helpful in understanding the possible CV impact these drugs may have on patients with diabetes.The dipeptidyl peptidase 4 (DPP-IV) inhibitors (sitagliptin, alogliptin, saxagliptin, linagliptin), two sodium-glucose co-transporter 2 (SGLT2) inhibitors (dapagliflozin and ertugliflozin) and two glucagon-like peptide 1 (GLP-1) receptor agonist (GLP-1 RA) drugs (lixisenatide and extended-release exenatide) have demonstrated non-inferiority on MACE outcomes with comparators – that is, they have assured CV safety when used in conjunction with other glucose-lowering treatment to improve glycaemic control. Four GLP-1 agonists (liraglutide, albiglutide, semaglutide and dula- glutide) and two SGLT2 inhibitors (empagliflozin and canagliflozin) have demonstrated CV benefit on MACE outcomes; such demonstration of superiority may be seen as evidence for benefit. The SGLT2 inhibitors canagliflozin, empagliflozin, dapagliflozin and ertugliflozin have all demonstrated a significant benefit in reducing the risk of hospitalisation due to heart failure (HHF) as a secondary/ exploratory outcome measure in their CVOTs. Further confirmation of benefit in heart failure independent of the presence of glucose intolerance has been demonstrated with dapagliflozin and empagliflozin in heart failure patients with or without diabetes. However, a comparable benefit in heart failure has not so far been seen in studies with the DPP-IV inhibitors or GLP-1 receptor agonists. Albiglutide is not available in the UK and may have little relevance to the practising clinician other than through the information it contributes about the possible mechanisms of action of GLP-1 RA medications.

Itaconic acid has been employed as a special facilitator to construct divalent metal ion based ionic crosslinking framework in the acrylonitrile butadiene rubber matrix. Readily accessible double bonds in itaconic acid could directly react with the elastomer to form effective covalent bonds. On the other hand, presence of easily dissociable protons in itaconic acid enables them to form ionic bonds that leads to an increase in crosslinking density of the vulcanizates. The synergistic effect of covalent crosslinking induced by peroxide and ionic crosslinking induced by metal carboxylate could effectively enhance the overall mechanical and dynamic mechanical properties of the rubber composites. In this study, three metal oxides, that is, zinc oxide, magnesium oxide, and calcium oxide, have been selected for this purpose. Tensile strength of nitrile rubber composites depends on the strength of ionic crosslinks, which in turn is influenced by the size of the alkaline earth metals, such as Mg, Ca, etc., and stoichiometric quantity of itaconic acid, which is at par in the formulation of this study. The novelty of this study is that the introduction of a dicarboxylic acid in combination with metal oxides enhances the crosslink density and tensile strength of nitrile rubber composites which could result from the metal organic framework.

To evaluate the lower labial minor salivary glands (MSGs) flow rate using fluorescein dye in healthy individuals and patients with Sjögren's syndrome (SS) and Stevens-Johnson syndrome (SJS).Thirty consecutive patients with SS (The mean salivary flow rate from the lower labial MSGs of normal individuals showed decade-wise decline (2.7 ± 0.29The fluorescein-assisted evaluation of the lower lip can be used as a quantitative method for measuring the labial salivary flow rate in SS and SJS patients.

Oxidative stress that damages cellular components affects various organs including the brain. It is thus believed to play an active role in neurodegenerative diseases, wherein the intrinsic antioxidant enzymes metabolize toxic intermediates. For therapeutic purpose, instead of antioxidant enzymes, small organic compounds as antioxidants may be more effective. Here, reducing power and electrochemical behavior of some flavanols, flavanonols, flavones, flavonols and O-methylated flavonols have been estimated and confirmed by the calculated bond dissociation energy. Compared to other classes, flavonols exhibited increased reducing power that decreased with methylation of the oxygen atom in the B-ring. Gossypetin emerged as the most effective of these flavonols. Generally, compounds with two hydroxyl groups in two consecutive positions of the phenyl ring and an enolic group in the C-ring with more preference for the hydroxyl group in the ortho position with respect to each other in the catechol moiety showed major activity. 5 position of the A-ring showed the least effect on the activity. The present understanding therefore may be applied for identifying compounds to be used as scaffold for designing potent antioxidants.

We have synthesized carbon-supported silver (Ag/C) nanobars by a simple surfactant-free hydrothermal method using glucose as the reducing reagent as well as the source of carbon in Ag/C nanobars. Physicochemical characterization of the materials was performed by X-ray Diffraction (XRD), field emission scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The XRD pattern confirmed the presence of a pure metallic silver phase. No carbon phase was detected, which indicates that the carbon exists mainly in the amorphous form. The electrocatalytic activity of Ag/C in different electrolyte solutions such as 0.5 M NaOH, 0.5 M NaOH + 1 M ethanol (EtOH), 0.5 M NaOH + 1 M ethylene glycol (EG), and 0.5 M NaOH + 0.01 M NaBH4 (sodium borohydride) was studied by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and chronoamperometry (CA) study. Alcohol tolerance of the catalysts was also established in the presence of ethanol and ethylene glycol. The forward-to-backward current ratio from cyclic voltammetry (CV) study of Ag/C-20 (20 h) in 0.5 M NaOH + 1 M ethanol solution at 100 mV s−1 scan rate is 4.13 times higher compared to that of Ag/C-5 (5 h). Hence, Ag/C-20 is a better candidate for the tolerance of ethanol. In the presence of ethylene glycol (1 M) in 0.5 M NaOH solution, it is obtained that the forward-to-backward current ratio at the same scan rate for Ag/C-20 is lower than that in the presence of ethanol. The durability of the catalyst was studied by chronoamperometry measurement. We studied the electrochemical kinetics of Ag/C catalysts for borohydride oxidation in an alkaline medium. The basic electrochemical results for borohydride oxidation show that Ag/C has very well strength and activity for direct borohydride oxidation in an alkaline medium. The reaction of borohydride oxidation with the contemporaneous BH4−. hydrolysis was noticed at the oxidized silver surface. Among all the synthesized Ag/C catalysts, Ag/C-20 exhibited the best electrocatalytic performance for borohydride oxidation in an alkaline medium. The activation energy and the number of exchange electrons at Ag/C-20 electrode surface for borohydride electro-oxidation were estimated as 57.2 kJ mol−1 and 2.27, respectively.

Three new zinc phosphites, [HIm]2[Zn3(HPO3)4] (1), [Zn2(HPO3)2Im2] (2), and [Zn(HPO3)Im] (3) (Im = imidazole), have been synthesized from the hydro/solvothermal reaction of zinc acetate, dimethyl phosphite, and imidazole by varying the temperature and solvent of the reaction medium. The structure of 1 is built from vertex-sharing of four HPO3-capped Zn3P3 units and adopts an open framework with 12-ring channels stabilized by HIm cations via N-H···O hydrogen bonds. For 2, the inorganic skeleton is comprised of alternating ZnO4 and HPO3 tetrahedra, while the coordinatively associated ZnN2O2 fragments occupy the 12-ring hexagonal channels. Compound 3 adopts a ladder-type one-dimensional structure and exhibits N-H···O hydrogen-bonding interactions to afford a supramolecular assembly. A plausible rationale on the genesis of 1-3 has been put forth by reacting the preformed inorganic zinc phosphites Zn{OP(O)(OMe)H}2 or [Zn2(HPO3)2(H2O)4]·H2O with imidazole as the structure-directing ligand. Alternating-current impedance measurements reveal that 1 and 3 exhibit proton conductivities on the order of 10-3-10-4 S cm-1 between 25 and 100 °C under 35 and 77% relative humidity in repeated impedance cycles (Ea = 0.22-0.35 eV). On the contrary, the conduction property is completely impaired in 2 under similar conditions.

The combination of semiconductor quantum dots (QD) and single-layer graphene (SLG) can lead to the formation of optoelectronic devices with enhanced sensitivity and can have extensive applications in the field of the photodetector and photovoltaics. The optical properties of the resultant hybrid material are controlled by the interplay of energy transfer between QDs and charge transfer between the QDs and SLG. By studying the steady-state and time-resolved photoluminescence spectroscopy of hybrid QD-SLG devices, we observe a subtle interplay of short- and long-range energy transfer between cadmium selenide (CdSe) QDs in a compact monolayer solid film placed in close proximity to an SLG and the charge transfer from the QD solid to SLG. At larger separation, I´, between the compact monolayer QD and SLG, the emission properties are dominated by mutual energy transfer between the QDs. At relatively smaller separation the emission from QDs, which is strongly quenched, is dominated by charge transfer between QDs and SLG. In addition, we are also able to tune the relative strength of energy and charge transfer by electrostatic doping through the back gate voltage, which provides a novel pathway to tune emission properties of these devices for possible applications as photodetectors, in photovoltaics, and for sensing. © 2021 American Chemical Society.

Objective: Caffeine (CAF) is one of the most commonly consumed nutritional stimulant in beverages. Interestingly, CAF produces varied effects in a dose-dependent manner, and that makes it one of th...

Neuroinflammation is associated with the development of depression. Deacetylases SIRT1 and SIRT2 are reported to exert neuroprotective effects in aging, neurogenesis, neurodegeneration and neuroinflammation. Therefore, this study aimed to investigate the effects of SIRT1 and SIRT2 modulators on LPS-induced neuroinflammation and neurodegeneration in vitro. To achieve this, HAPI rat microglial cells were pre-treated with the SIRT1 activator resveratrol (0.1–20 µM), the selective SIRT1 inhibitor EX527 (0.1; 1 µM), the dual SIRT1/SIRT2 inhibitor sirtinol (0.1–20 µM) and the SIRT2 inhibitor AGK2 (0.1; 1 µM), prior to exposure with LPS (5 ng/mL) for 20 h. The reference antidepressant drug fluoxetine and the nonsteroidal anti-inflammatory drug ibuprofen were also evaluated in the same paradigm, both at 1 μM. Resveratrol and sirtinol inhibited TNF-α production to a greater degree than either fluoxetine or ibuprofen. Resveratrol, sirtinol, EX527 and AGK2 significantly reduced PGE2 production by up to 100% in microglia. Then, the supernatant was transferred to treat SH-SY5Y cells for 24 h. In all cases, SIRT modulator pretreatment significantly protected undifferentiated SH-SY5Y human neuroblastoma cells from the insult of LPS-stimulated HAPI supernatant by up to 40%. Moreover, resveratrol and sirtinol also showed significantly better neuroprotection than fluoxetine or ibuprofen by up to 83 and 69%, respectively. In differentiated SH-SY5Y cells, only sirtinol (20, 10 µM) and AGK2 (0.1 µM) pretreatment protected the cells from LPS-stimulated HAPI supernatant. This study suggests that SIRT1 and SIRT2 modulators are effective in inhibiting LPS-stimulated production of TNF-α and PGE2 in HAPI microglial cells and protecting SH-SY5Y cells from inflammation. Thus, we provide proof of concept for further investigation of the therapeutic effect of SIRT1 and SIRT2 modulators and combination with current antidepressant medication as a treatment option.

In the present study, pristine magnesium aluminium layered double hydroxide (Mg-Al LDH, sample A) nanoparticles were synthesized by simple co-precipitation technique followed by intercalation of me...