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The flavone apigenin (APG), alone as well as in combination with other chemotherapeutic agents, is known to exhibit potential anticancer effects in various tumors and inhibit growth and metastasis of melanoma. However, the potential of apigenin nanoparticles (APG-NPs) to prevent lung colonization of malignant melanoma has not been well investigated. APG-loaded PLGA-NPs were surface-functionalized with meso-2,3-dimercaptosuccinic acid (DMSA) for the treatment of melanoma lung metastasis. DMSA-conjugated APG-loaded NPs (DMSA-APG-NPs) administered by an oral route exhibited sustained APG release and showed considerable enhancement of plasma half-life, Cmax value, and bioavailability compared to APG-NPs both in plasma and the lungs. DMSA-conjugated APG-NPs showed comparably higher cellular internalization in B16F10 and A549 cell lines compared to that of plain NPs. Increased cytotoxicity was observed for DMSA-APG-NPs compared to APG-NPs in A549 cells. This difference between the two formulations was lower in B16F10 cells. Significant depolarization of mitochondrial transmembrane potential and an enhanced level of caspase activity were observed in B16F10 cells treated with DMSA-APG-NPs compared to APG-NPs as well. Western blot analysis of various proteins was performed to understand the mechanism of apoptosis as well as prevention of melanoma cell migration and invasion. DMSA conjugation substantially increased accumulation of DMSA-APG-NPs given by an intravenous route in the lungs compared to APG-NPs at 6 and 8 h. This was also corroborated by scintigraphic imaging studies with radiolabeled formulations administered by an intravenous route. Conjugation also allowed comparatively higher penetration as evident from an in vitro three-dimensional tumor spheroid model study. Finally, the potential therapeutic efficacy of the formulation was established in experimental B16F10 lung metastases, which suggested an improved bioavailability with enhanced antitumor and antimetastasis efficacy of DMSA-conjugated APG-NPs following oral administration.

Photosynthetic efficiency and sink demand are tightly correlated with rates of phloem loading where maintaining low cytosolic sugar concentrations is paramount to prevent downregulation of photosynthesis. Sugars Will Eventually be Exported Transporters (SWEETs) are thought to have a pivotal role in apoplastic phloem loading of C4 grasses. SWEETs have not been well-studied in C4 species, and their investigation is complicated by photosynthesis taking place across two cell types and therefore, photoassimilate export can occur out of either one. SWEET13 homologues in C4 grasses have been proposed to facilitate apoplastic phloem loading. Here we provide evidence for this hypothesis using the C4 grass Setaria viridis. Expression analyses on the leaf gradient of C4 species Setaria and sorghum show abundant transcript levels for SWEET13 homologues. Carbohydrate profiling along the Setaria leaf show total sugar content to be significantly higher in the mature leaf tip compared with the younger tissue at the base. We present the first known immunolocalization results for SvSWEET13a and SvSWEET13b using novel isoform-specific antisera. These results show localization to the bundle sheath and phloem parenchyma cells of both minor and major veins. We further present the first transport kinetics study of C4 monocot SWEETs by utilizing a Xenopus laevis oocyte heterologous expression system. We demonstrate that SvSWEET13a and SvSWEET13b are high-capacity transporters of glucose and sucrose with a higher apparent Vmax for sucrose than glucose, typical of clade III SWEETs. Collectively, these results provide evidence for an apoplastic phloem loading pathway in Setaria and possibly other C4 species.

Despite the many recent advances in disposable and wearable sensing technologies for point of care testing (POCT), few affordable, flexible, and disposable sensors are available for the detection of tyrosine (Tyr), a valuable biomarker for metabolic and neurodegenerative diseases. In this regard, the disposable screen-printed electrodes on flexible substrates are attractive. However, current screen-printed approaches for the detection of Tyr use rigid ceramic substrates, expensive metal nanoparticle conductive inks and stiff metal or metal oxide-based sensitive materials, that are not suitable for single-use disposable or wearable POCT devices. To address these challenges, this work presents a flexible and disposable electrochemical sensor using graphene oxide – chitosan (GO-CS) modified carbon-based electrodes for the detection of Tyr. The affordable and easy to fabricate sensor consists of a three-carbon electrode system screen printed on a flexible, low-cost polyvinyl chloride (PVC) substrate. GO and CS were chosen as the sensitive nanocomposite due to their natural abundance and excellent electrochemical sensing properties. Quantitative determination of Tyr using DPV revealed a linear proportional response between 1 and 100 μM, with a correlation coefficient of 0.9993. The GO-CS-screen-printed carbon sensor (SPCS) also offers a linear range detection limit of 5.86 μM, and excellent sensitivity (0.0846 μA μM-1) and repeatability (RSD = 4.02%). The GO-CS-SPCS thereby provides a promising platform for the active sensing elements of single-use, disposable, and wearable POCT devices suitable for early diagnosis and monitoring of metabolic or neurodegenerative diseases or nutritional management.

Cadmium(II) is an omnipresent environmental toxicant emitted from various industrial sources and by anthropogenic sources such as smoking. Cadmium(II) enters our body through various sources including contaminated food and drinks and from active or passive smoking. It spares no organs in our body and the calamities it invites include primarily nephrotoxicity, osteotoxicity, teratogenicity, endocrine disruption, hepatotoxicity and carcinogenicity above all. It brings about a bolt from the blue in the cellular biochemistry by generating reactive oxygen species (ROS), disrupting the factors involved in the repair of DNA lesions and many other toxic nuisances otherwise by modulating the cell signalling machinery and acting as a potent carcinogen above all. In this review, we have tried to decipher some of the mechanisms played by cadmium(II) in exhibiting its toxic effects on various system of our body.

RECQ1 is the shortest among the five human RecQ helicases comprising of two RecA like domains, a zinc-binding domain and a RecQ C-terminal domain containing the winged-helix (WH). Mutations or deletions on the tip of a β-hairpin located in the WH domain are known to abolish the unwinding activity. Interestingly, the same mutations on the β-hairpin of annealing incompetent RECQ1 mutant (RECQ1T1) have been reported to restore its annealing activity. In an attempt to unravel the strand annealing mechanism, we have crystallized a fragment of RECQ1 encompassing D2–Zn–WH domains harbouring mutations on the β-hairpin. From our crystal structure data and interface analysis, we have demonstrated that an α-helix located in zinc-binding domain potentially interacts with residues of WH domain, which plays a significant role in strand annealing activity. We have shown that deletion of the α-helix or mutation of specific residues on it restores strand annealing activity of annealing deficient constructs of RECQ1. Our results also demonstrate that mutations on the α-helix induce conformational changes and affects DNA stimulated ATP hydrolysis and unwinding activity of RECQ1. Our study, for the first time, provides insight into the conformational requirements of the WH domain for efficient strand annealing by human RECQ1.

A set of metal carbonyl cluster-boronic acid conjugates of the group VIII metals (Fe, Ru, and Os) were synthesized and their antiproliferative effects measured against two breast cancer cell lines (MCF-7 and MDA-MB-231) and a noncancerous breast epithelial (MCF-10A) cell line. The cytotoxicity followed the order Ru > Os > Fe for the MDA-MB-231 cells, although the latter two exhibited similar cytotoxicity against MCF-7 and MCF-10A cells. The osmium species {Os3(CO)10(μ-H)[μ-SC6H4-p-B(OH)2]} (2) could be chemically oxidized to its hydroxy analogue [Os3(CO)10(μ-H)(μ-SC6H4-p-OH)] (2-OH), which showed comparable cytotoxicity. Mode of action studies pointed to an apoptotic pathway for cell death. Ministry of Education (MOE) Nanyang Technological University Published version This work was supported by Nanyang Technological University and the Ministry of Education (Research grant no. RG121/18).

We present here a metal-free, visible-light- and triphenylphosphine-mediated intermolecular, reductive amination between nitroarenes and boronic acids at ambient temperature without any photocatalyst. Mechanistically, a slow reduction of nitroarenes to a nitroso and, finally, a nitrene intermediate occurs that leads to the amination product with concomitant 1,2-aryl/-alkyl migration from a boronate complex. A wide range of nitroarenes underwent C-N coupling with aryl-/alkylboronic acids providing high yields.

The synthesis and characterization of an imino-pyridyl ligand N,N'-(butane-1,4-diyl)bis(1-(pyridin-2-yl)methanimine) (L) and its Ag(I)ClO4 complex (I) by various spectroscopic techniques and elemental analyses is presented in this study. X-ray single crystal structure of complex I revealed that in complex I, each Ag(I) ion is tetra coordinated with two pyridine N-atoms and two imine N-atoms of the ligand L, forming a macrocyclic dimeric Ag(I) grid. In the macrocyclic dimer complex I, Ag-Ag separation along the chain is 5.318 Å. The Ag-Npy average distance is 2.396 Å and that of the Ag-Nim is 2.257 Å. The macrocyclic dimer complex I is supramolecularly arranged by π-stacking interactions. Computational, Hirshfeld surface analysis and photophysical studies on ligand L and complex I have also been performed. Crystal data for C32H36Ag2Cl2N8O8 (M =947.33 g/mol): Triclinic, space group P-1 (no. 2), a = 9.1714(12) Å, b = 10.4373(14) Å, c = 10.8297(14) Å, α = 112.317(3)°, β = 91.391(3)°, γ = 92.353(3)°, V = 957.3(2) Å3, Z = 1, T = 293.15 K, μ(MoKα) = 1.220 mm-1, Dcalc = 1.643 g/cm3, 10248 reflections measured (4.07° ≤ 2Θ ≤ 53.098°), 3966 unique (Rint = 0.0280, Rsigma = 0.0331) which were used in all calculations. The final R1 was 0.0722 (I > 2σ(I)) and wR2 was 0.2229 (all data).

Background Multiple myeloma (MM) is an incurable hematologic malignancy, and outcomes remain poor for patients with triple-class relapsed/refractory MM (RRMM). Descriptive analyses were performed on available data for patient characteristics, disease course, and outcomes of the KCd on triple-class RRMM patients at our institution. Patients and methods Twenty-three patients with triple-class RRMM treated with KCd between June 2017 and October 2020 were included in our analysis. The regimen KCd consisted of 28 days cycles of carfilzomib 20/36 mg/m2 IV on days 1, 2, 8, 9, 15, and 16, cyclophosphamide 300 mg/m2 IV weekly, and dexamethasone (20-40) mg orally weekly. Results Patients received a median of 6 (3-10) prior regimens. The median number of cycles administered was 4 (1-11) cycles. Overall response rate was 52%, 6 patients (26%) achieved very good partial response (VGPR), 6 patients (26%) achieved partial response (PR), and 5 patients (22%) achieved stable disease (SD). Progression-free survival (PFS) and Overall-survival (OS) were 4 and 11.9 months, respectively. There was no reported treatment-related mortality. The most common grade ≥3 adverse events were neutropenia (26%), thrombocytopenia (56.5%), and anemia (56.5%). Conclusions KCd showed clinically meaningful efficacy and manageable safety profile in patients with triple-class RRMM in real-world.

The tetraruthenium tetrahydrido carbonyl cluster Ru4(µ-H)4(CO)12 (1) reacts with diphenylvinylphosphine under thermal activation to give the substitution products Ru4(µ-H)4(CO)12−n(κ1-Ph2PCH=CH2)n, (2) (n = 3 (a); 4 (b)). Both 2a and 2b have been completely characterized, including by single-crystal X-ray diffraction analysis. Each of the diphenylvinylphosphine ligands in 2a and 2b is terminally bound, via the phosphorus atom, to a different ruthenium metal center, while the hydride positions in the Ru4(µ-H)4 cores retain the D2d symmetry of the parent cluster 1. Clusters 2a and 2b were able to retain their structural integrity at elevated temperatures. Graphic Abstract: Thermolysis of Ru4(μ-H)4(CO)12 (1) in cyclohexane with diphenylvinylphosphine afforded the tri- and tetra-substituted derivatives Ru4(μ-H)4(CO)9(κ1-Ph2PCH=CH2)3 (2a) and Ru4(μ-H)4(CO)8(κ1-Ph2PCH=CH2)4 (2b). For both substituted clusters, the diphenylvinylphosphine ligands are bound terminally to the tetraruthenium core via the phosphorus atoms while the hydride positions retain the D2d symmetry of the parent cluster 1.[Figure not available: see fulltext.] Ministry of Education (MOE) Nanyang Technological University This work was supported by Hwa Chong Institution as well as Nanyang Technological University and the Ministry of Education with a research Grant (No. M4011158).

Hybrid nanoarchitectures of AgInS2 and TiO2 photocatalysts were prepared by using a modified sol–gel method. The experimental results reveal that these nanocomposites display enhanced visible light absorption and effective charge carrier separation compared to their pristine parent samples (AgInS2 or TiO2). 0.5 wt % AgInS2 loading was found to be the optimum concentration for photocatalytic applications. More than 95% of doxycycline degradation was achieved within 180 min of solar light illumination. Similarly, the dopant concentrations at lower values (

Endocannabinoids are key bioactive components of the endocannabinoid system, and the profound influence of endocannabinoids on the modulation of the immune system is being increasingly appreciated. The knowledge of endocannabinoid–immune cell crosstalk will pave the way to therapeutic implications of modulators of this pathway in autoimmune and chronic inflammatory disorders. Endocannabinoids seem to exert both anti‐inflammatory and pro‐inflammatory effects in specific contexts, based on specific receptor engagement and the downstream signalling pathways involved. In this review, we summarized the biosynthesis, signalling and degradation of two well‐studied endocannabinoids—anandamide and 2‐arachidonylglycerol in immune cells. Then, we discussed the effects of these two endocannabinoids on the functioning of major innate and adaptive immune cells, along with the choice of receptors employed in such interactions. Finally, we outline our current knowledge on the involvement of anandamide and 2‐arachidonylglycerol in context of inflammation, allergies, autoimmunity and metabolic disorders.

Nanocellulose, a biopolymer, has received wide attention from researchers owing to its superior physicochemical properties, such as high mechanical strength, low density, biodegradability, and biocompatibility. Nanocellulose can be extracted from wide range of sources, including plants, bacteria, and algae. Depending on the extraction process and dimensions (diameter and length), they are categorized into three main types: cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and bacterial nanocellulose (BNC). CNCs are a highly crystalline and needle-like structure, whereas CNFs have both amorphous and crystalline regions in their network. BNC is the purest form of nanocellulose. The nanocellulose properties can be tuned by chemical functionalization, which increases its applicability in biomedical applications. This review highlights the fabrication of different surface-modified nanocellulose to deliver active molecules, such as drugs, proteins, and plasmids. Nanocellulose-mediated delivery of active molecules is profoundly affected by its topographical structure and the interaction between the loaded molecules and nanocellulose. The applications of nanocellulose and its composites in tissue engineering have been discussed. Finally, the review is concluded with further opportunities and challenges in nanocellulose-mediated delivery of active molecules., Graphical abstract Image 1, Highlights - Surface modification of nanocellulose with various acids and oxidizing agents. - Efficient and targeted delivery of nanocellulose-conjugated drugs, plasmids, and proteins. - Application of nanocellulose-based nanohybrids for tissue engineering. - Opportunities and challenges of using nanocellulose as polymer matrix.

The ability to rationally design and predictably construct crystalline solids has been the hallmark of crystal engineering research. To date, numerous examples of multicomponent crystals comprising organic molecules have been reported. However, the crystal engineering of cocrystals comprising both organic and inorganic chemical units is still poorly understood and mostly unexplored. Here, we report a new diverse set of higher‐order cocrystals (HOCs) based on the structurally versatile—yet largely unexplored—phosph(V/V)azane heterosynthon building block. The novel ternary and quaternary cocrystals reported are held together by synergistic and orthogonal intermolecular interactions. Notably, the HOCs can be readily obtained either via sequential or one‐pot mechanochemical methods. Computational modelling methods reveal that the HOCs are thermodynamically driven to form and that their mechanical properties strongly depend on the composition and intermolecular forces in the crystal, offering untapped potential for optimizing material properties., Mechanosynthesis gives ternary and quaternary hybrid organic‐inorganic cocrystals held together via synergistic intermolecular interactions. Notably, higher‐order ternary and quaternary cocrystals can be readily obtained either via serial synthetic routes from the individual components or via one‐pot approaches.

Mercury (Hg) exists in the environment as inorganic (metallic Hg vapor, mercurous and mercuric salts) or organic (bonded to a structure containing carbon atoms) forms. Neurotoxic effect of Hg is known for years. While the organic form (methylmercury (meHg)) led to the Minamata incidence in Japan and “wonder-wheat” disaster in Iraq, the “mad hatters” and “Danbury shakes” were related to the inorganic elemental form (Hg vapor). Human exposure to toxic Hg continues in the modern world to a large extent by artisanal gold mining, biomass combustion, chloralkali production, and indigenous medicine use to name a few. Heavy industrial use of Hg contaminates air and landfills, affecting the aquatic ecosystem and marine food chain. A detailed social and occupational history with a high index of clinical suspicion is required to not miss this toxic etiology for movement disorders like ataxia, tremor, or myoclonus. In this review, we have discussed the past and present global health impact of Hg from a movement disorder perspective. The connection of Hg with neurodegeneration and autoimmunity has been highlighted. We have also discussed the role of chelating agents and the preventive strategies to combat the neurotoxic effects of Hg in the modern world.

Several toll-like receptors (TLRs) reside inside endosomes of specific immune cells-among them, aberrant activation of TLR7 and TLR9 is implicated in myriad contexts of autoimmune diseases, making them promising therapeutic targets. However, small-molecule TLR7 and TLR9 antagonists are not yet available for clinical use. We illustrate here the importance of C2, C6, and N9 substitutions in the purine scaffold for antagonism to TLR7 and TLR9 through structure-activity relationship studies using cellular reporter assays and functional studies on primary human immune cells. Further in vitro and in vivo pharmacokinetic studies identified an orally bioavailable lead compound 29, with IC50 values of 0.08 and 2.66 μM against TLR9 and TLR7, respectively. Isothermal titration calorimetry excluded direct TLR ligand-antagonist interactions. In vivo antagonism efficacy against mouse TLR9 and therapeutic efficacy in a preclinical murine model of psoriasis highlighted the potential of compound 29 as a therapeutic candidate in relevant autoimmune contexts.

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.

Cryogenic carbon dioxide (CO2) capture technologies showed promising results for the purification of highly sour natural gas reserves. However, quantitative experimental data for solid and liquid CO2 formation during cryogenic separation is not adequately examined in the previous studies. Moreover, an economical and efficient cryogenic CO2 capture technology with reduced energy and hydrocarbon losses is necessary to make it attractive for commercial use. A high-pressure cryogenic hybrid network comprised of the packed bed and the cryogenic separator was developed for the cryogenic experimental study on CO2 capture from binary CO2-CH4 mixture to focus these areas. Feed containing 30, 50 and 70 % CO2 content were used and the separation study was conducted in vapor-solid (V-S), vapor-liquid (V-L), and vapor-liquid-solid (V-L-S) regions of phase equilibria. The packed bed was used in the V-S operational domain to quantify CO2 solid up to 20 bar because of the operational limitations. Separation characteristics and V-L isothermal flash measurements at 20, 30, and 40 bar pressure and temperature ranges from -20 to −60 °C were carried out in the cryogenic separator. The operation in the setups was carried out at different compositions of the CH4-CO2 binary mixture to define the boundaries of the hybrid cryogenic network. Liquid formation at 40 bar for 70% CO2 feed was 0.15 kg at -55 °C as compared to 0.03 kg for 30 % CO2 feed. The simulation study was carried out using Aspen Plus along with the Peng Robinson Equation of State (EoS), and the results were compared with the experimental data, which showed good agreement. The hybrid cryogenic network showed an energy reduction of 37 % compared to the conventional cryogenic distillation network with 90.6 to 97.3 % CH4 purity and 2.65 to 12.39 % methane losses with different arrangements of the hybrid cryogenic network.

A unique, tailor-made, zwitterionic, dual thermoresponsive and fluorescent microgel probe was synthesized via Reversible Addition Fragmentation chain-Transfer (RAFT) polymerization. Microgels were pre pared via oil in water (o/w) emulsion polymerization where poly(carboxybetaine) (PCB) acted as a macro-RAFT reagent as well as an emulsifier. The presence of poly(N-vinylcaprolactam) (PNVCL) in the microgel system imparts the thermoresponsiveness to the system and the presence of a rhodamine derivative as fluorophore makes it responsive to pH change of the system by showing a fluorescence emission at 580 nm (reddish orange color). The dual thermoresponsiveness [i.e. the presence of upper critical solution temperature (UCST @ 12 degrees C) as well as lower critical solution temperature (LCST @ 33 degrees C)] of the microgels was studied via UV-visible spectroscopy (UV-vis) and temperature responsive dynamic light scattering (DLS) analyses. Presence of the PCB in the corona-crosslinked microgel, played a vital role in the formation of self-assembled structure as well as in protein immobilization (antifouling activity). Antifouling property was studied using UV-vis spectroscopy where bovine serum albumin (BSA) was taken as a model protein. The presence of the pH-responsive fluorescence, thermoresponsiveness as well as antifouling properties makes this zwitterionic microgel system a potential a potential candidate for medical diagnostics and for drug delivery vehicles. (c) 2020 Elsevier Inc. All rights reserved.

Androgen deprivation therapy (ADT) combined with docetaxel or antiandrogens (abiraterone, enzalutamide, or apalutamide) improved the outcomes in men with metastatic hormone-sensitive prostate cancer (mHSPC). When multiple options are available, the dilemma remains how to choose among these options. Similarly, issues of bone health, long-term side effects of therapies, and hereditary risk need to be discussed for comprehensive care. In the present article, we reviewed the relevant evidence for the treatment of mHSPC. ADT alone is not the current standard of care for most patients. In these times of plenty and price crisis, it is imperative to find the best option for treating these patients.

Nanocellulose-assisted gold nanoparticles are considered promising materials for developing eco-friendly diagnostic tools for biosensing applications. In this study, we synthesized 2,2,6,6-tetramethylpiperidin-1-piperidinyloxy (TEMPO)-oxidized cellulose nanocrystal (TEMPO-CNC)-capped gold nanoparticles (AuNPs) for the colorimetric detection of unamplified pathogenic DNA oligomers of methicillin-resistant Staphylococcus aureus. The fabricated TEMPO-CNC-AuNPs (TC-AuNPs) were characterized using UV-visible spectroscopy, transmission electron microscopy, atomic force microscopy, and dynamic light scattering. The average diameter of the synthesized AuNPs was approximately 30 nm. The aqueous solution of TC-AuNPs was stable and exhibited an absorption peak at 520 nm. The chemical interaction between TC-AuNPs and the surface charge of the target and non-target DNA determined the colorimetric differences under ionic conditions. A dramatic color change (red → blue) was observed in the TC-AuNP solution with the target DNA under ionic conditions due to the aggregation of AuNPs. However, no observable color change occurred in the TC-AuNP solution with the non-target DNA under similar conditions owing to the better shielding effects of the charged moieties. The colorimetric detection limit of the TC-AuNPs was demonstrated to be as low as 20 fM pathogenic DNA. Therefore, the use of TEMPO-oxidized CNC-capped AuNPs is efficient and straightforward as a biosensor for the colorimetric detection of pathogenic DNA.

Chitosan-based hydrogels have received significant interest in tissue engineering and regenerative medicine applications owing to their superior biocompatibility. However, their applications are restricted owing to their weak mechanical strength. Cellulose nanocrystals (CNCs) are often explored as reinforcing agents to improve the native properties of polymers owing to their superior physicochemical properties. We fabricated a multi-functional hydrogel scaffold of chitosan/CNCs by incorporating different amounts of CNCs into a chitosan (CH) hydrogel. Significant enhancement in the mechanical strength was noted in the CH/CNCs as compared to that in pure CH hydrogel scaffolds. The cytocompatibility of the fabricated scaffolds was monitored in the presence of bone-marrow-derived mesenchymal stem cells (BMSCs). Improved cell viability and mineralization were observed with CH/CNC hydrogel scaffolds than those with pure CH hydrogel scaffolds. Enhanced osteogenic-related gene expression was observed in the CH/CNC hydrogel scaffold environment than that in the control, indicating their osteogenic potential, in addition to enhanced antibacterial activity. Developed composite scaffolds exhibited improved sustained drug release compared to that by pure polymer scaffolds, and this was more sustained in the scaffolds with higher CNC content. Therefore, the fabricated scaffolds may have been used in tissue engineering for osteogenesis, as antibacterial agents, and in sustained drug delivery.

Androgen-disruptors are chemicals that interfere with the biosynthesis, metabolism or function of endogenous androgens affecting normal male reproductive development and health. Several epidemiological studies have indicated a link between exposure to androgen disrupting chemicals with reduced sperm counts and increased infertility. The actions of androgens within target cells are transduced by the androgen receptors (ARs). Chlorpyrifos (CPF), a chlorinated organophosphorus pesticide, is known to cause impairment in both male and female reproductive systems. Recent publications have shown molecular interactions of CPF and its environmental degradation products with human progesterone receptor and human estrogen receptor. Exposure to CPF causes a marked reduction in sperm counts with lowering in serum testosterone level, which suggests possible molecular interaction of CPF with AR. The investigation to reveal the possibility and the extent of binding of CPF and some of its degradation products (chlorpyrifos-oxon [CPYO], desethyl chlorpyrifos [DEC], trichloromethoxypyridine [TMP] and trichloropyridinol [TCP]) with AR using molecular docking simulation are reported. The findings of the present docking, binding energy and molecular dynamics studies reveal that CPF and its degradation products may bind to ARs and act as a potent androgen disruptor.Communicated by Ramaswamy H. Sarma.

Purpose This analysis evaluated the relationship between concentrations of quizartinib and its active metabolite AC886 and QT interval corrected using Fridericia’s formula (QTcF) in patients with relapsed/refractory acute myeloid leukemia (AML) treated in the phase 3 QuANTUM-R study (NCT02039726). Methods The analysis dataset included 226 patients with AML. Quizartinib dihydrochloride was administered as daily doses of 20, 30, and 60 mg. Nonlinear mixed-effects modeling was performed using observed quizartinib and AC886 concentrations and time-matched mean electrocardiogram measurements. Results Observed QTcF increased with quizartinib and AC886 concentrations; the relationship was best described by a nonlinear maximum effect (Emax) model. The predicted mean increase in QTcF at the maximum concentration of quizartinib and AC886 associated with 60 mg/day was 21.1 ms (90% CI, 18.3–23.6 ms). Age, body weight, sex, race, baseline QTcF, QT-prolonging drug use, hypomagnesemia, and hypocalcemia were not significant predictors of QTcF. Hypokalemia (serum potassium Conclusion QTcF increase was dependent on quizartinib and AC886 concentrations, but patient factors, including sex and age, did not affect the concentration–QTcF relationship. Because concomitant strong cytochrome P450 3A (CYP3A) inhibitor use significantly increases quizartinib concentration, these results support the clinical recommendation of quizartinib dose reduction in patients concurrently receiving a strong CYP3A inhibitor. Clinical Trial Registration NCT02039726 (registered January 20, 2014).

In modern organic synthesis, the execution of reactions in the absence of expensive transition metals has received significant attention from the view-point of green chemistry and sustainable development. As a consequence, the combination of MI-TBHP as an oxidation system (M = Na, K, NH4) has opened a new avenue with significant impact for the succinct synthesis of complex heterocycle molecules via the construction of various chemical bonds [C-X (X = C, N, S, O), N-X (X = N, P) and S-N]. This comprehensive review article delineates the progress of recent developments in this emerging area, with an in-depth discussion on the substrate scope, limitations and proper mechanistic underpinnings. We hope this review will highlight the great potential of this MI-TBHP as a powerful oxidation system and inspire researchers to conduct further endeavors in this domain.

Cyclobutadiene (CBD) is the paradigmatic antiaromatic molecule but is known to form highly stable aromatic complexes, e.g. CBD-Fe(CO)3. This intriguing reversal of aromaticity from antiaromatic to aromatic terrain during the complexation process cannot be appropriately handled with single-reference-based theoretical techniques. We explore this aromaticity reversal, for the first time, by a detailed aromaticity analysis using magnetically induced current densities (MICD) and nucleus independent chemical shifts (NICS) using genuine ab initio multi-reference wavefunction-based theory. We trace the dramatic change of aromaticity for a prototypical cyclobutadiene complex, CBD-CH+ (CH+Fe(CO)3), considering a 3D potential energy surface for two independent parameters, namely the approach of CH+ and the automerization cross-section of cyclobutadiene. The 3D potential energy surfaces indicate the presence of a conical intersection/avoided crossing between the ground and the first excited state. The plot of aromaticity indices and the corresponding numerical values show that the change of aromaticity indices is drastic around the conical intersection/avoided crossing and automerization of cyclobutadiene plays a crucial role in the formation of cyclobutadiene complexes. Computations on analogous CBD-Be and CBD-CO systems (Be/COFe(CO)3) emphasize the generality of the conclusions drawn from the CBD-CH+ system.

Synthesis of linearly fused aromatic systems using a glycal-based diene with an aryne is a long-standing topic of interest in glycal chemistry. We have examined the mechanistic pathways for the transformation of substituted glycals to chiral fused aromatic cores via Diels–Alder (DA) reaction using the SMDACN-M06-2X/6-31G(d) level of theory. The DA reactions of E (1a) and Z (1a′) forms of C-2 alkenyl glycal and an aryl glycal (1b) as a diene were examined with a benzyne intermediate generated as a dienophile. The computational results reveal that 1a and 1b can only be transformed into the fused aromatic cores by the base-catalyzed reaction because a [1,5] sigmatropic hydrogen shift is not feasible. The activation free energy barrier for the base-catalyzed proton abstraction process is 4.2 kcal mol−1 and there is almost no barrier for stereoisomeric 1a DA-complexes. The activation free energy barrier values for stereoisomeric 1b DA-complexes for the base-catalyzed proton abstraction process are 10.8 and 12.4 kcal mol−1. The appropriate orientation of glycal-ring-oxygen and hydrogen at the 5th position of Z (1a′) forms of C-2 alkenyl glycal facilitates the [1,5] sigmatropic hydrogen shift; however, the base-catalyzed reaction is energetically more favored than the former case. The rate-determining step for 1a and 1a′ is the ring-opening step (18.2 and 19.5 kcal mol−1 for the S-stereoisomer), whereas the DA adduct formation step is the rate-determining step for 1b (16.1 kcal mol−1 for the S-stereoisomer). The structural analysis reveals the formation of the preferred S-stereoisomer over the R-stereoisomer with the respective dienes.

Stereoelectronic effects are crucial in governing the conformational behaviour of small molecules bearing heterocyclic rings adjacent to amides. It dictates the antagonist and agonist activity for G-protein coupled receptor (C3aR) of inflammatory protein complement C3a on human macrophages. We have examined the role of non-covalent attractive interactions of heteroatoms of heterocycles adjacent to amides in the antagonists of C3a receptor (C3aR) using the CBS-QB3 and M06-2X/aug-cc-pVDZ levels of theory. The contribution of orbital interaction (n → σ* delocalization) towards the stability of antagonist has been examined and the systems were designed for the clear preference of such molecules to bind with C3aR protein. The molecular electrostatic potential (MESP) analysis also revealed the presence of Sigma-holes (σ-holes) in such systems interacting with the amide oxygen and contributed to the stability of the cis-conformation responsible for the antagonist behavior of such molecules. The –CF3 substituted electron-withdrawing group attached to the carbon atom of the –C–X bond enhanced the attractive non-covalent interaction between X(heterocycle) and O(amide) and electrostatic interactions that contribute to the stability of the cis-conformation of the antagonists. The –CF3 substituted selenazole ring (6Se-a) was stabilized by ∼4.0 kcal mol−1 than the other corresponding possible conformations. The non-covalent interaction (NCI) plot corroborates the non-covalent interactions between the heteroatoms in such molecules. The docking study performed with ligands L-1 and L-2 showed improved interaction with C3aR compared to those with the reported SB290157. Importantly, the cis-conformation of the ligands L-1 and L-2 persisted in the C3aR environment. The influence of the stereoelectronic effect on conformations of small ligands acting as antagonists towards G-protein coupled C3aR has been highlighted to design new candidates with better efficacy.

Introduction: In the present study a novel series of twelve 1-(aryl)-2-(1H-imidazol-1-yl)methanones 3(a-l) were synthesized and characterised by physicochemical and spectral analysis,viz. elemental analysis, IR spectroscopy, NMR spectroscopy. The antibacterial property of the compounds were examined, in order to develop new broad spectrum antibiotics. Methods: The compounds 3(a-l) were synthesised by reacting the corresponding 2-(aryl)-1H-imidazoles 2 with substituted benzoyl chlorides. Binding mode analysis of the most active compound was carried out. Predictive ADME studies were carried out for all the compounds. Results and Discussions: Among the synthesized compounds, (2-(3-nitrophenyl) (2,4-dichlorophenyl) -1Himidazol-1-yl)methanone 3i exhibited highest antibacterial activity. Binding mode analysis of the highest active compound was carried out in the active site of glucosamine-6-phosphate synthase (2VF5).

Anthocyanin pigments are readily degraded during processing and storage of foodstuffs that can have a dramatic impact on color quality and may also affect the nutritional properties. Total anthocyanin pigment content and indices for polymeric color and browning are easily measured with simple spectrophotometric methods. Once individual pigments are identified, their changes can be monitored by high-performance liquid chromatography (HPLC). The edible fruits of 12 plants were extracted in methanol and subjected to solvent–solvent partitioning to yield three fractions, hexane, ethyl acetate, and aqueous. A number of factors affecting anthocyanin stability and color are discussed in this review. Anthocyanins are probably the most spectacular of plant pigments since they are responsible for most of the red, purple and blue pigmentation of flowers, hits and vegetables. However, because of their highly reactive nature, anthocyanins readily degrade, or react with other constituents in the media, to form colorless or brown colored compounds. The presence of an oxonium ion adjacent to carbon 2 makes the anthocyanins particularly susceptible to nucleophilic attack by such compounds as sulfur dioxide, ascorbic acid, hydrogen peroxide and even water. Loss of anthocyanin pigmentation also occurs in the presence of oxygen and various enzymes, and as a result of high temperature processing. Certain degree of pigment stabilization may be conferred by acylation with various organic acids, co pigmentation, self-association and/or metal chelation. In addition, pH has a marked effect on anthocyanin stability, and on the color of media containing these pigments. A number of anthocyanin-rich sources have been investigated for their potential as commercial pigment extracts. Although their application is primarily limited to acidic media, continued research on the chemistry of anthocyanins may lead to application and stabilization of these pigments in a wider variety of food products.

Selective adsorption of CO2 from flue gas is extremely significant because of its increasing concentration in air and its deleterious effect on the environment. In this work, we have explored metal-ion-bound prismane molecules for selective CO2 adsorption from the flue gas mixture. The Ca2+-bound prismane complex exhibits superior CO2 selectivity and adsorption capacity. The calculated binding energy and molecular electrostatic potential (MESP) analysis showed that the rectangular face of prismane binds strongly with metal ions as compared to its triangular face. The CBS-QB3 and density functional theory-based functional M06-2X/6-311+G(d) calculations show that the prismane molecule can bind to one Li+, K+, Mg2+, and Ca2+ ion with favorable binding energy. The metal-ion-bound prismane complexes have been examined for their CO2, N2, and CH4 adsorption capacity. Prismane-Ca2+ can bind with six CO2 molecules strongly with an average binding energy of -18.1 kcal/mole as compared to six N2 (-12.6) and five CH4 (-13.4) gas molecules. The gravimetric density calculated for the CO2-adsorbed prismane-Ca2+ complex has been found to be 69.1 wt %. The discrete hydrocarbon structure for selective separation of CO2 is rare in the literature and can have potential applications for cost-effective CO2 capture from the flue gas mixture.

The accumulation of ammonia in poultry houses is of concern to bird and human health. Acidification of the litter by application of acidifying amendments such as sodium bisulfate (SBS) retains ammonia generated by microbial degradation of uric acid as harmless ammonium in the litter. Although some studies on the effects of litter amendments on specific bacteria and groups of bacteria have been carried out previously, wide gaps in knowledge remain. In the present study, 2 types of samples were prepared and either left unamended or amended with 2.5 or 10% SBS. One set of samples consisted of a 1:1 mixture of built-up litter and fresh poultry manure (L/M); the other of fresh wood shavings and fresh poultry manure (S/M). The samples were kept in the laboratory at room temperature for 35 d. The pH of unamended mixtures increased to 7.3 and 6.9 for L/M and S/M, respectively. A pH of 6.7 and 3.9 on day 35 was observed for L/M and SM with 2.5% SBS, respectively. The corresponding values for LM and SM amended with 10% SBS were 3.5 and 2.5, respectively. Plating data indicated that coliforms became less numerous in the unamended samples than the SBS-amended samples. This difference was also seen in data obtained by high-throughput sequencing of 16S rDNA. The sequencing data also indicated that sequences from the genus Oceanisphaera accounted for as much as 80% of the sequences from L/M and about 40% of those from S/M samples early on. Sequences from members of the order Clostridiales were enriched in L/M and S/M amended with 10% SBS as were sequences from the genus Turicibacter. Weisella species sequences were more prevalent in SBS-amended samples than in unamended ones. Sequences from the genus Corynebacterium, Brachybacterium, and Arthrobacter were more common in L/M samples than in S/M samples regardless of the SBS content. The data indicate that litter amendments affect some bacteria populations and not others. Further studies are required to determine if the observed population changes such as increased survival of coliforms warrant actions to improve the microbial quality of litter to be reused.

Background: The recent outbreak of the novel SARS-CoV-2 across the globe and the absence of specific drug against this virus lead the scientific community to look into some alternative indigenous treatments. India as a hub of Ayurvedic and medicinal plants can shed light on its treatment using specific active bio-molecules from these plants. Objectives: Keeping our herbal resources in mind, we were interested to inquire whether some phytochemicals from Indian spices and medicinal plants can be used as alternative therapeutic agents in contrast to synthetic drugs. Materials and methods: We used in silico molecular docking approach to test whether bioactive molecules of herbal origin such as hyperoside, nimbaflavone, ursolic acid, 6-gingerol, 6-shogaol and 6-paradol, curcumin, catechins and epigallocatechin, α-Hederin, piperine could bind and potentially block the Mproenzyme of the SARS-CoV-2 virus. Results: Ursolic acid showed the highest docking score (−8.7 kcal/mol) followed by hyperoside (−8.6 kcal/mol), α-Hederin (−8.5 kcal/mol) and nimbaflavone (−8.0 kcal/mol). epigallocatechin, catechins, and curcumin also exhibited high binding affinity (Docking score −7.3, −7.1 and −7.1 kcal/mol) with the Mpro. The remaining tested phytochemicals exhibited moderate binding and inhibitory effects. Conclusion: This finding provides a basis for biochemical assay of tested bioactive molecules on SARS-CoV-2 virus.

Nanosheet gate-all-around (GAA) field-effect transistor (NSFET) is a potential replacement for the FinFET at advanced technology nodes owing to better control of short-channel effects and higher drive current. Due to the increased complexity of the GAA stacked structure, new forms of process variability come into the picture, which are dominant over the conventional process variability such as metal gate granularity (MGG) and line edge roughness (LER) for FinFETs. In this article, we show one such process variability called as metal thickness variation (MTV). MTV causes WF mymargin variations on the gates of the GAA sheet transistor and results in a significant ${V}_{T}$ variability. The impact of MTV is studied using an analytical framework. We studied three variants of NSFETs and reported variability in terms of key device design parameters such as intersheet spacing and metal thicknesses. The results presented here help in designing the process flow for a type of NSFET to minimize the ${V}_{T}$ variability.

Three new hetero-metallic copper(II)-manganese(II) complexes, [(CuL)2 Mn3 (C6 H5 CO2 )6 ] (1), [(CuL)2 Mn(CH3 CO2 )2 ] (2), and {[(CuL)2 Mn(C6 H5 CH2 CO2 )2 ] ⋅ 2CH3 CN} (3), have been synthesized using [CuL] as ''metalloligand'' (where H2 L=N,N'-bis(2-hydroxynaphthyl-methylidene)-1,3-propanediamine). Single-crystal structural analyses show an almost linear penta-nuclear structure for complex 1 where a square planar [CuL] unit is connected to each of the two terminal MnII ions of a linear, centrosymmetric [Mn3 (benzoate)6 ] unit through the double phenoxido bridges. Both complexes 2 and 3 possess a linear tri-nuclear structure where two terminal square-pyramidal [CuL] units are bonded to the central MnII ion through double phenoxido oxygen atoms along with a syn-syn bridging acetate (for 2)/phenyl acetate (for 3). All three complexes exhibit catecholase, and phenoxazinone synthase-like activities under aerial conditions. For catecholase like activity, the turnover numbers (kcat ) are 595, 40, and 205 h-1 whereas, for phenoxazinone synthase like activity, the turnover numbers are 25, 4, and 11 h-1 for complexes 1-3, respectively. The mechanism of both catalytic oxidase activities is proposed on the basis of mass spectral evidences. Variable-temperature (2-300 K) dc molar magnetic susceptibility measurements of 1 reveal antiferromagnetic interactions between the Cu-Mn centres (J1 =-29.3 cm-1 ), and also between the Mn-Mn centres of the [Mn3 (benzoate)6 ] unit (J2 =-0.68 cm-1 ). On increasing the magnetic field at 2 K, its ground spin state changes from S=3/2 to S=5/2 at 4 T, attributable to the low value of J2 which makes the excited spin states close in energy with the ground spin state. Complexes 2 and 3 show antiferromagnetic coupling interactions between the Cu-Mn pairs with J values of -9.51, and -5.32 cm-1 , respectively.

Arsenic is a highly carcinogenic environmental contaminant. Curcumin, the bioactive component of turmeric, exhibits therapeutic efficacy against several chronic inflammatory and infectious diseases. The present study was carried out to investigate the impact of arsenic on eye lens and evaluate the ameliorative potential of curcumin against arsenic toxicity. Gene expression analysis of α, β, and γ-crystallins and fatty acid profile of lens tissues of arsenic-exposed Labeo rohita was examined and the protective effect of curcumin as diet supplement was evaluated. Curcumin-supplemented diet was prepared at 1.5% and 3% and fed to four groups of fish for 7 days prior to arsenic exposure (at 5 ppm and 15 ppm) for 15 days. Gene expression analysis showed downregulation of α and β-crystallins in the eye lens of arsenic-exposed groups (fed basal diet), whereas the groups fed a curcumin-supplemented diet showed insignificant alterations. Similarly, fatty acid fingerprint of lens lipids arsenic-exposed group exhibited reduction in saturated fatty acid and docosahexaenoic acid (DHA) content. However, in 3% curcumin-supplemented diet–fed and arsenic exposed group group, fatty acid profile remained unchanged. Interestingly, concentration of one non-fatty acid, an antioxidant compound (phenol 2,4-bis 1,1 dimethyl; PD) that was identified in the GC-MS fingerprinting through NIST library (version 2.2, 2014), decreased in response to arsenic exposure which was restored to normal level in curcumin-supplemented groups proving the therapeutic potential of curcumin. The findings of the study suggest that curcumin has a protective effect on eye lens against arsenic toxicity.

Every year about millions of tons of raw feedstocks having a potential value in solid waste is confined into landfills. One of the present challenges for ecological engineering is to develop econom...

New findings What is the central question of this study? Does treatment of hypoxic dams with a placenta-targeted antioxidant prevent the release of placenta-derived factors that impair maturation or growth of fetal cardiomyocytes in vitro? What is the main finding and its importance? Factors released from hypoxic placentae impaired fetal cardiomyocyte maturation (induced terminal differentiation) and growth (increased cell size) in vitro, which was prevented by maternal treatment with a placenta-targeted antioxidant (nMitoQ). Moreover, there were no sex differences in the effects of placental factors on fetal cardiomyocyte maturation and growth. Overall, our data suggest that treatment targeted against placental oxidative stress could prevent fetal programming of cardiac diseases via the release of placental factors. Abstract Pregnancy complications associated with placental oxidative stress may impair fetal organ development through the release of placenta-derived factors into the fetal circulation. We assessed the effect of factors secreted from placentae previously exposed to prenatal hypoxia on fetal cardiomyocyte development and developed a treatment strategy that targets placental oxidative stress by encapsulating the antioxidant MitoQ into nanoparticles (nMitoQ). We used a rat model of prenatal hypoxia (gestational day (GD) 15-21), which was treated with saline or nMitoQ on GD15. On GD21, placentae were harvested, placed in culture, and conditioned medium (containing placenta-derived factors) was collected after 24 h. This conditioned medium was then added to cultured cardiomyocytes from control dam fetuses. Conditioned medium from prenatally hypoxic placentae increased the percentage of binucleated cardiomyocytes (marker of terminal differentiation) and the size of mononucleated and binucleated cardiomyocytes (sign of hypertrophy), effects that were prevented by nMitoQ treatment. Our data suggest that factors derived from placentae previously exposed to prenatal hypoxia lead to abnormal fetal cardiomyocyte development, and show that treatment against placental oxidative stress may prevent fetal programming of cardiac disease.

Curcumin is an important molecule with a plethora of pharmacological activities and therapeutic potentials. Despite its efficacy, it remained a potential drug candidate owing to hydrolytic instability and poor aqueous solubility. To overcome the limitations related to low solubility, low bioavailability, and the fact that curcumin is never present in solution as a "single unit", its complex was prepared with MnII with the idea that binding to a metal ion might help to resolve these issues. The complex was characterized by elemental and spectral analysis. The structure of the complex was determined by density functional theory calculations. The complex was stable at physiological buffer conditions, unlike curcumin. It did not have any detrimental effect on mammalian cells. There was a significant enhancement in the antibacterial activity of the complex compared to curcumin against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. It showed a strong affinity for deoxyribonucleic acid (DNA) evident from a high binding constant value with calf thymus DNA and also from the retarded electrophoretic mobility of bacterial plasmid DNA. The complex showed "superoxide dismutase-like" activity leading to the generation of reactive oxygen species (ROS). The complex caused bacterial membrane perturbation evident from calcein leakage assay, which was further corroborated by scanning and transmission electron microscopic experiments. Overall, the present study shows improved stability and antibacterial potency of a nontoxic complex over curcumin. Its multitargeting mode of action such as ROS-production, effective binding with DNA, and permeabilization of bacterial membrane together allows it to be an effective antibacterial agent that could be taken further for therapeutic use against bacterial infections.

Wood is prone to fire attack making its application restricted as building material. The current study aims to evaluate the effect of double step chemical modification on Pinus radiata using Dimeth...

The properties of the oxide/AlGaN heterointerface are investigated from field-dependent off-state degradation and recovery in thermally grown NiOx-, TiO2-, and Al2O3-based metal-oxide-semiconductor...

Copper oxide (CuO) nanoflowers were synthesized by a reproducible and inexpensive wet chemical method. The synthesized CuO nanoflowers were characterized by x-ray diffraction, Raman spectroscopy, x-ray photoelectron spectroscopy, field emission scanning electron microscopy and energy-dispersive spectroscopy. For an optimized operating temperature of 240°C, the sensor characteristics of the gas sensing device were measured using acetone as a volatile gas. The synthesized CuO nanoflower-based gas sensor responded very strongly for acetone gas concentrations in the range of 250–2250 ppm, and the recorded response for concentrations of 250 ppm and 2250 ppm was 2.7 and 7.2, respectively. The stability of the synthesized sensor was checked by repeating the measurements over a period of 1 month, and a very small change of 3.3% in the response of the sensor was observed.

Chlorpyrifos is an extensively used organophosphate pesticide showing broad-spectrum effectiveness on various target pests. Long-term sublethal exposure to this pesticide is reported to produce detrimental effects on sex hormone metabolism and nervous system functioning. It is a suspected endocrine-disrupting chemical and causes abnormal developmental patterns, gonadal atrophy, and neurodevelopmental problems. The degradation products formed during environmental degradation of chlorpyrifos are also capable of binding with steroid hormone receptors such as estrogen receptor alpha (ER-α) and can disrupt estrogen signaling in humans. In the present study, chlorpyrifos and four of its degradation products viz. CPYO, DEC, TCP, and TMP were chosen to study their ability to bind with estrogen receptors. The molecular docking and dynamics simulation carried out to understand the molecular interaction of chlorpyrifos and its environmental degradation products with human ER reveal the risk of potential disruption in estrogen signaling in humans by these compounds.

Herbal medicine is gaining its popularity day by day and gradually streaming toward integration into the mainstream healthcare systems. Therefore, standardization of herbal formulations is essential in order to assess quality of the drugs. Two commonly used paradigms, compound and pattern-based approaches, were performed to ensure quality and hence product consistency. A rapid, sensitive, and reproducible high-performance thin-layer chromatography (HPTLC) method has been developed for one of the major bioactive markers, piperine. The plates were developed using the mobile phase with toluene–ethyl acetate–formic acid–methanol (3:3:0.8:0.2, v/v). The method was validated for limit of detection, limit of quantification, linearity, specificity, precession, and recovery. The results indicate that the bioactive compound was present in 2.64% w/w in the fruit of Piper nigrum Linn. and 0.253% in a herbal formulation. Each ingredient was analyzed vis-a-vis the herbal formulation and the reflectance spectrum of the matching component(s) to ensure the presence of each ingredient in the herbal formulation. The individual component adding up has also resulted similar fingerprint pattern as that of herbal formulation. Thus, the TLC method could be a rapid tool for the delineation of each individual ingredient in the finished products for authenticity, efficacy, and for batch-to-batch consistency.

Quizartinib is an FMS‐like tyrosine kinase 3 (FLT3) inhibitor that has shown robust clinical activity in patients with FLT3‐internal tandem duplication–mutated relapsed/refractory acute myeloid leukemia (AML). This analysis evaluated the population pharmacokinetics (PK) of quizartinib and its active metabolite, AC886, in a pooled analysis of data from 649 healthy volunteers or patients with AML from 8 clinical trials including the phase 3 QuANTUM‐R study. Quizartinib was given as a single dose or multiple once‐daily doses of 20, 30, 60, or 90 mg. Nonlinear mixed‐effects modeling was performed using observed concentrations of quizartinib and AC886. Strong CYP3A inhibitor use resulted in an 82% increase in the area under the curve (AUC) and a 72% increase in the maximum concentration (Cmax) of quizartinib. Albumin level, age, and body surface area were statistically significant covariates on quizartinib PK. However, their individual effects on quizartinib AUC and Cmax were