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ACS omega 8(15), 13690 - 13701 (2023). doi:10.1021/acsomega.2c07869, L10-ordered FeNi, tetrataenite, found naturally in meteorites is a predilection for next-generation rare-earth free permanent magnetic materials. However, the synthesis of this phase remains unattainable in an industrially relevant time frame due to the sluggish diffusion of Fe and Ni near the order–disorder temperature (593 K) of L1$_0$ FeNi. The present work describes the synthesis of ordered L1$_0$ FeNi from elemental Fe and Ni powders by mechanical alloying up to 12 h and subsequent heat treatment at 623 K for 1000 h without a magnetic field and for 4 h in the presence of 1.5 T magnetic field. Also, to address the ambiguity of L1$_0$ phase identification caused by the low difference in the X-ray scattering factor of Fe and Ni, synchrotron-based X-ray diffraction is employed, which reveals that 6 h milling is sufficient to induce L1$_0$ FeNi formation. Further milling for 12 h is done to achieve a chemically homogeneous powder. The phase fraction of L1$_0$-ordered FeNi is quantified to ∼9 wt % for 12 h milled FeNi, which increases to ∼15 wt % after heat treatment. Heat treatment of the milled powder in a magnetic field increases the long-range order parameter (S) from 0.18 to 0.30. Further, the study of magnetic properties reveals a decrease in magnetic saturation and a slight increase in coercivity with the increase in milling duration. At the same time, heat treatment in the magnetic field shows a considerable increase in coercivity., Published by ACS Publications, Washington, DC

The carboxy-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin ligase and co-chaperone belonging to Ubox family that plays a crucial role in the maintenance of cellular homeostasis by switching the equilibrium of the folding-refolding mechanism towards the proteasomal or lysosomal degradation pathway. It links molecular chaperones viz. HSC70, HSP70 and HSP90 with ubiquitin proteasome system (UPS), acts as a quality control system. CHIP contains charged domain in between N-terminal TPR and C-terminal Ubox domain. TPR domain interacts with the aberrant client proteins via chaperones while Ubox domain facilitates the ubiquitin transfer to the client proteins for ubiquitination. Thus, CHIP is a classic molecule that executes ubiquitination for degradation of client proteins. Further, CHIP has been found to be indulged in cellular differentiation, proliferation, metastasis and tumorigenesis. Additionally, CHIP can play its dual role as a tumor suppressor as well as an oncogene in numerous malignancies, thus acts as a double agent. Here, in this review, we have reported almost all substrates of CHIP established till date and classified them according to the hallmarks of cancer. In addition, we discussed about its architectural alignment, tissue specific expression, sub-cellular localization, folding-refolding mechanisms of client proteins, E4 ligase activity, normal physiological roles, involvement in various diseases and tumor biology. Further, we aim to discuss its importance in HSP90 inhibitors mediated cancer therapy. Thus, this report concludes that CHIP may be a promising and worthy drug target towards pharmaceutical industry for drug development.

One of the more active areas in bioorganometallic chemistry is the preparation and reactivity studies of active site mimics of the [NiFe]-hydrogenases. One area of particular recent progress involves reactions that interconvert Ni(μ-X)Fe centers for X = OH, H, CO, as described by Song et al. Such reactions illustrate new ways to access intermediates related to the Ni-R and Ni-SI states of the enzyme. Most models are derivatives of the type (diphosphine)Ni(SR)2Fe(CO)3-n(PR′3)n. In recent work, the methodology has been generalized to include FeII(diphosphine) derivatives of Ni(N2S2), where N2S22- is the tetradentate diamine-dithiolate (CH2N(CH3)CH2CH2S-)2. Indeed, models based on Ni(N2S2) have proven valuable, but these studies also highlight challenges in working with heterobimetallic complexes, specifically the tendency of some such Ni-Fe complexes to convert to homometalliic Ni-Ni derivatives. This kind of problem is not readily detected by X-ray crystallography. With this caution in mind, we argue that one series of complexes recently described in this journal are almost certainly misassigned.

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.

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.

Female-female nonsexual interference competition is a major fitness determinant of biased sex ratio groups with high female density. What strategies can females use to overcome the negative impact of this competition? To answer this question we used flour beetles (

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

Hypothesis: Deposits of biofluid droplets on surfaces (such as respiratory droplets formed during an expiratory) are composed of water-based salt-protein solution that may also contain an infection (bacterial/viral). The final patterns of the deposit formed and bacterial aggregation on the deposits are dictated by the fluid composition and flow dynamics within the droplet. Experiments: This work reports the spatio-temporal, topological regulation of deposits of respiratory fluid droplets and control of bacterial aggregation by tweaking flow inside droplets using non-contact vapor-mediated interactions. Desiccated respiratory droplets form deposits with haphazard multiscale dendritic, cruciform-shaped precipitates when evaporated on a glass substrate. However, we showcase that short and long-range vapor-mediated interaction between the droplets can be used as a tool to control these deposits at nano-micro-millimeter scales. We morphologically control hierarchial dendrite size, orientation and subsequently suppress cruciform-shaped crystals by placing a droplet of ethanol in the vicinity of the biofluid droplet. Active living matter in respiratory fluids like bacteria is preferentially segregated and agglomerated without its viability and pathogenesis attenuation. Findings: The nucleation sites can be controlled via preferential transfer of solutes in the droplets; thus, achieving control over crystal occurrence, growth dynamics, and the final topology of the deposit. For the first time, we have experimentally presented a proof-of-concept to control the aggregation of live active matter like bacteria without any direct contact. The methodology can have ramifications in biomedical applications like disease detection and bacterial segregation.

In the first results from an ongoing global cancer screening data repository, screening program organization was better overall in Europe compared to other continents; however, there were substantial gaps in implementation across both high- and low-resource settings. The CanScreen5 project is a global cancer screening data repository that aims to report the status and performance of breast, cervical and colorectal cancer screening programs using a harmonized set of criteria and indicators. Data collected mainly from the Ministry of Health in each country underwent quality validation and ultimately became publicly available through a Web-based portal. Until September 2022, 84 participating countries reported data for breast (n = 57), cervical (n = 75) or colorectal (n = 51) cancer screening programs in the repository. Substantial heterogeneity was observed regarding program organization and performance. Reported screening coverage ranged from 1.7% (Bangladesh) to 85.5% (England, United Kingdom) for breast cancer, from 2.1% (Cote d'Ivoire) to 86.3% (Sweden) for cervical cancer, and from 0.6% (Hungary) to 64.5% (the Netherlands) for colorectal cancer screening programs. Large variability was observed regarding compliance to further assessment of screening programs and detection rates reported for precancers and cancers. A concern is lack of data to estimate performance indicators across the screening continuum. This underscores the need for programs to incorporate quality assurance protocols supported by robust information systems. Program organization requires improvement in resource-limited settings, where screening is likely to be resource-stratified and tailored to country-specific situations.

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.

Pseudomonas aeruginosa (PA) is part of a group of common nosocomial pathogens that exhibit multidrug resistance, thus proving to be a significant threat to healthcare. This study analyzes the ability of four commonly used antibiotics to observe eradication of the PA biofilm growth. Ceftazidime (CAZ), Tobramycin (TOB), Ofloxacin (OFLX), Meropenem (MEM), were tested against overnight cultures of PA strain PA01. The minimal inhibitory concentrations (MIC) of planktonic cells for all the four antibiotics were determined using broth microdilution while the minimal bactericidal concentrations (MBCs) were determined by colony count after antibiotic treatment and regrowth. Biofilm growth inhibition was performed by treating cells with antibiotic at the time of inoculation while eradication was determined by adding antibiotics 24 hours after inoculation, allowing mature biofilm formation, followed by the measurement of absorbance. PA planktonic cells exhibited highest susceptibility to MEM compared to overnight grown PA biofilm which demonstrated resistance to CAZ, complete sensitivity to ofloxacin, and minimal sensitivity to TOB and MEM. PA biofilm displayed dose-dependent sensitivity to TOB, MEM and OFLX, and a significant level of resistance to CAZ during inhibition phase. However, in the eradication phase, PA showed significant resistance to TOB followed by CAZ while PA biofilm showed sensitivity at higher concentrations of MEM. Our study exhibits that PA strain PA01 is resistant to ceftazidime in both planktonic and biofilm phases. While ofloxacin proved to be the most effective even at lower concentrations when compared with other antibiotics, tobramycin was most effective at higher concentrations for eradicating and inhibiting PA biofilms.

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

In the context of obesity-induced adipose tissue inflammation, migration of macrophages and their polarization from predominantly anti-inflammatory to proinflammatory subtype is considered a pivotal event in the loss of adipose insulin sensitivity. Two major chemoattractants, monocyte chemoattractant protein-1 (MCP-1) and Fetuin A (FetA), have been reported to stimulate macrophage migration into inflamed adipose tissue instigating inflammation. Moreover, FetA could notably modulate macrophage polarization, yet the mechanism(s) is unknown. The present study was undertaken to elucidate the mechanistic pathway involved in the actions of FetA and MCP-1 in obese adipose tissue. We found that FetA knockdown in high fat diet (HFD) fed mice could significantly subdue the augmented MCP-1 expression and reduce adipose tissue macrophage (ATM) content thereby indicating that MCP-1 is being regulated by FetA. Additionally, knockdown of FetA in HFD mice impeded the expression of inducible nitric oxide synthase (iNOS) reverting macrophage activation from mostly proinflammatory to anti-inflammatory state. It was observed that the stimulating effect of FetA on MCP-1 and iNOS was mediated through interferon γ (IFNγ) induced activation of JAK2-STAT1-NOX4 pathway. Furthermore, we detected that the enhanced IFNγ expression was accounted by the stimulatory effect of FetA upon the activities of both cJun and JNK. Taken together, our findings revealed that obesity-induced FetA acts as a master upstream regulator of adipose tissue inflammation by regulating MCP-1 and iNOS expression through JNK-cJun-IFNγ-JAK2-STAT1 signaling pathway. This study opened a new horizon in understanding the regulation of ATM content and activation in conditions of obesity-induced insulin resistance.

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).

Divalent mercury (Hg2+) is highly toxic in nature and extensively found in different natural water bodies worldwide. Thus, rapid trace-level monitoring of Hg2+, as well as its effective removal fro...

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

Phosphorus (P) is an essential macronutrient required for the survival and reproduction of all living organisms. Its inorganic form (Pi) is taken up by the roots to support plant growth and development, and its availability directly determines agricultural productivity. The primary source of P replenishment in agriculture is chemical phosphate (Pi) fertilizers. While application of Pi-fertilizers to croplands ensures high yield agriculture, its intensive use leads to several environmental implications, including loss of soil fertility and pollution of water bodies with runoff fertilizer. Global non-renewable P-reserves are finite and would last for only a few hundred years. Therefore, a holistic approach is needed to combine Pi-use efficient germplasm with the targeted fertilization, agronomically superior fertilizer formulations for better P-management. The latest technologies to reclaim Pi from alternative sources need to be explored. In the present review, we first outline the challenges and environmental consequences of Pi-intensive fertilization, followed by plants' response and adaptive strategies to Pi starvation. Next, we discuss the role of microbes and Pi-nanofertilizer to plant Pi nutrition. Finally, a few cutting-edge technologies and innovative solutions available for reclaiming Pi from waste are argued.

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.

The particle shape and size distribution of inorganic fillers play a crucial role in the scaffold buildability when those are incorporated in the viscoelastic polymers. In order to address this issue, the phase pure rod-shaped nanocrystalline hydroxyapatite (HAp) powders with varying particle sizes and shapes were synthesized by a one-pot hydrothermal method without any regulatory surfactant at an initial solution pH of 9. As-synthesized nanocrystalline HAp particles (0�5 wt) were incorporated into 15 wt pre-cross-linked gelatin methacryloyl (GelMA) hydrogel matrix to fabricate a predesigned scaffold architecture using a custom-made 3D bioprinter. The printing parameters (nozzle diameter, extrusion pressure, and printing speed) were optimized for each composition. The biophysical properties (uniaxial compression behavior, swelling ratio, and in vitro degradation) of the composite hydrogel scaffolds were critically analyzed to unravel the role of nano-sized HAp addition. The compression strength and modulus were substantially improved, while the rate of water uptake and bio-enzymatic degradation significantly reduced with HAp content. We propose that the inorganic�organic nanocomposite hydrogel could be efficiently assembled to formulate a potential bioink for 3D bioprinting applications toward tissue regeneration. © 2021 The American Ceramic Society

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.

Energy harvesting from natural resources has gained much attention due to the huge increase in the demand for portable electronic devices and the shortage of conventional energy resources in general. In the present work, the fabrication and realistic applications of a piezoelectric nanogenerator (PENG) using polydimethylsiloxane (PDMS) and the abundantly available, environment-friendly natural fiber Sonchus asper (SA) have been discussed. The biocompatible, low-cost SA fibers were flexible enough and showed high piezoelectric properties as active materials in the study. The SA pappus based piezoelectric nanogenerator demonstrated its ability to convert the harvested biomechanical energy into electrical energy from the various mechanical energy sources available in our environment. The SA pappus/PDMS thin film based piezoelectric nanogenerator (SPENG) fabricated in the laboratory showed colossal output performances (open circuit output voltage, V OC ∼81.2 V; short circuit current, I SC ∼1.0 μA) by continuous finger impartation. Uniform output performance was also obtained by the application of uniform force on the devices (e.g., ∼42 V for 5 N force at 10 Hz frequency). The SPENG was capable to charge a 2.2 μF capacitor to 3.2 V within a short time span (16 s) under continuous finger impartation and illuminate 39 commercial high-power blue LEDs that were connected in series. Thus, the fabricated SPENG can be used as a green and portable energy source to power up portable electronic devices. Apart from this, the SPENG may also be used as a self-powered energy supply for pacemakers or different types of health care units if properly improvised.

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.

Lipophile induced modulations of self-assembly characteristics in aqueous Pluronic systems merit attention because of wide-ranging uses of Pluronics as solubilizing agents of lipophilic substances. In this paper, we report unusual evolutions of structural and hydration properties in lavender essential oil (LO) solubilized Pluronic P85 aqueous micellar systems as a function of micellar volume fraction and temperature. Our DLS, SANS, and viscometry studies show that the spherical-to-wormlike micellar structural transition observed in 1% P85 solutions upon solubilization of LO quite unexpectedly gets suppressed with increased P85 concentration to ≥5%. Detailed SANS studies reveal that the core sizes of the oil solubilized micelles cannot attain the threshold value required for the onset of structural transition at higher copolymer concentrations due to their progressive shrinking with an increase in P85 concentration. Oil solubilized P85 solutions show two cloud points and very interestingly exhibit micellar growth upon cooling to their lower cloud points. Steady state fluorescence studies explain this based on increasing dehydration of micellar corona with a decrease in temperature, very much opposite to what is observed in pure aqueous Pluronic systems. The results give new insight into viscous flow properties and low temperature storage possibilities of oil solubilized aqueous Pluronic systems.

Hydrogen production in the microfluidic alkaline membraneless electrolyzer (μAME) marks a new paradigm in sustainable energy technology. One challenge in this field is implementing a bifunctional c...

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.

Highly photosensitive epoxy-based polymer SU8 is becoming extensively used for MicroElectro-Mechanical Systems (MEMS) and microfluidic devices not only as a negative photoresist but also as the basic constitutional material because of the easy fabrication of devices with tailored dimensions from µm to mm sizes. Here, we have shown a one-step process for the fabrication of thin cantilever arrays of thickness upto 1-2 µm using MASKLESS GRAYSCALE LITHOGRAPHY (MGL). Microfabricated polymeric disposable cantilevers can be utilized for label-free biochemical sensing with desirable advantages such as high sensitivity due to low Young’s modulus, low cost compared to its Silicon counterpart and ease in reproducible fabrication. Microcantilever arrays of different shapes were fabricated reproducibly by optimizing the process parameters. Arrays of suspended cantilevers can be used for the fabrication of chemical/biochemical sensors as SU-8 is highly resistant to chemicals and biocompatible making it a suitable material for such sensors.

In this work, a facile hydrothermal treatment has been followed to develop In2S3 nanosheets doped with 0–2 mol% cerium. Morphological and structural analyses have revealed the development of highly crystalline smooth In2S3 nanosheets upon 1 mol% cerium doping. The substitutionally doped cerium ions have led to hybridization of the Ce 4f and In 5p orbitals resulting in downshift of the conduction band edge thus aiding in higher photon absorption for enhanced photocatalytic activity. Such characteristics have been deduced from the UV-vis spectra and further theoretically verified by employing first principles density functional theory (DFT) calculations to obtain density of states (DOS) plots of computationally constructed 1 mol% Ce doped In2S3 structures. Transient photocurrent responses have been obtained and photocatalytic degradation of neurotoxic drug ciprofloxacin has been performed to demonstrate the enhanced photocatalytic and photoelectrocatalytic potential of cerium doped samples. The marked improvement showed a rapid decline in the 2 mol% Ce doped samples, due to the limited solubility of cerium ions in the In2S3 lattice leading to structural deformities upon excess cerium doping. Thus, the synergistic influence of indium and cerium atoms in In2S3 nanocompounds for solar energy applications has been established by various experimental analyses complemented with theoretical investigations via DFT calculations.

Different small molecules and nanomaterials have been known as inhibitors of protein misfolding and subsequent fibrillation, which marks the initiation of various degenerative conditions. This work explores the effect of polyphenol-capped gold nanoparticles on the extent of human serum albumin fibrillation. Silymarin-capped (SAuNPs), quercetin-capped (QAuNPs) and gallic acid-capped gold nanoparticles (GAuNPs) were synthesized with a uniform size range and their relative antioxidant capacity was determined through DPPH assay. The fibrillation of HSA at 65 °C was inhibited by ∼15% in the presence of SAuNPs and the process was monitored through a combination of Thioflavin T fluorescence spectroscopy, circular dichroism spectroscopy and microscopic analysis. The inhibitory effect appeared much pronounced in the case of QAuNPs (∼67%) and GAuNPs (∼60%). Using SDS PAGE analysis, we demonstrated that the different inhibitory activity of SAuNPs, QAuNPs, and GAuNPs could be attributed to the antioxidant potential of the individual nanoparticles. Our work revealed that apart from protein–nanoparticle surface interactions, the antioxidant capacity has a role in determining the effectiveness of a protein fibrillation inhibitor. Cytotoxic analysis of protein–gold nanoparticle aggregates on HaCaT cell lines further confirmed that the nanoparticles were biosafe and can be considered as active therapeutics for translational use.

Among synthetic biomaterials, calcium phosphate (CaP)-based bioceramics, specifically hydroxyapatite (HA) and tricalcium phosphate (TCP) as well as biphasic calcium phosphate (BCP), are widely investigated in the biomedical community. The arrangement of different ions in the CaP crystal structure allows one to dope with metal ions, while tailoring the properties. The present article reviews some of the multifaceted research in the field of (multi)-ion-doped BCP, particularly on the aspects of biomedical applications. After summarizing different synthesis methods, a brief overview of experimental techniques and results to probe the dopant site and local structure surrounding the dopants has been provided, with an emphasis on the XRD-based Rietveld refinement and EXAFS (extended X-ray absorption fine structure) method. The effect of ion substitution on the functional properties, such as dielectric and magnetic behavior, of BCP has also been discussed. Importantly, in vitro and in vivo biocompatibility of do...