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Background and aim Epithelial ovarian cancer has the deadliest prognosis amongst gynaecological cancers, warranting an unmet need for newer drug targets. Based on its anticancer as well as abortifacient potential, Moringa oleifera Lam. root was hypothesized to have some implications in follicle stimulating hormone receptor (FSHR) dependent cancers like epithelial ovarian cancer. Experimental procedure Effect of Moringa oleifera Lam. root extract (MRE) was studied in epithelial ovarian cancer cell line through in vitro studies viz. MTT assay, clonogenic assay, cell cycle analysis, flow cytometry, western blot analysis, immunocytochemical analysis of FSHRand c-Myc expression and in vivo studies viz. effect of MRE in mice model of ovarian carcinoma. The structure of the active compound of MRE was elucidated following solvent extraction, purification through column chromatography, preparative TLC and bioactivity guided structural identification through 1H-NMR, 13C-NMR, DEPT-135, ESIMS,FT-IR spectrophotometry, UV–vis–NIR spectrophotometry and DFT study. Results and conclusion Crude MRE displayed cytotoxic activity, induced apoptosis, and attenuated expression of FSHR and c-Myc in ovarian cancer cell line OAW42. MRE also attenuated expression of CD31, FSHR, and c-Myc in tumour xenograft mouse model. Finally, the active compound purified from ethyl acetate-n-hexane subfraction ofMRE, that attenuated viability of ovarian carcinoma cell lines and reduced FSHR and c-Myc expression, was identified as a naturally hydrated-trifattyglyceride, showing aDFT-optimized folded amphipathic structure for easy transportation through hydrophilic and hydrophobic regions in a biological system, indicating its immense therapeutic relevance in epithelial ovarian carcinoma.

Packaging paternal genome into tiny sperm nuclei during spermatogenesis requires 10sup6/sup-fold compaction of DNA, corresponding to a 10-20 times higher compaction than in somatic cells. While such a high level of compaction involves protamine, a small arginine-rich basic protein, the precise mechanism at play is still unclear. Effective pair potential calculations and large-scale molecular dynamics simulations using a simple idealized model incorporating solely electrostatic and steric interactions clearly demonstrate a reversible control on DNA condensates formation by varying the protamine-to-DNA ratio. Microscopic states and condensate structures occurring in semidilute solutions of short DNA fragments are in good agreement with experimental phase diagram and cryoTEM observations. The reversible microscopic mechanisms induced by protamination modulation should provide valuable information to improve a mechanistic understanding of early and intermediate stages of spermatogenesis where an interplay between condensation and liquid-liquid phase separation triggered by protamine expression and post-translational regulation might occur. Moreover, recent vaccines to prevent virus infections and cancers using protamine as a packaging and depackaging agent might be fine-tuned for improved efficiency using a protamination control.

N-Heterocyclic carbene-catalyzed tandem Stetter-aldol reaction of phthalaldehyde and α,β-unsaturated ketimines has been developed to afford functionalized naphthalen-1(2H)-one derivatives as the formal [4+2] annulation product. Interestingly, the reaction of aldimines led to the formation of isoquinoline derivatives instead of the expected indanone derivatives as a [4+1] annulation product.

The separation of linear from branched hydrocarbons is often required in many situations. There are several methods through which they can be separated but none provides a very high degree of purity or works without considerable expenditure of energy. Recently, a novel method was proposed to separate a mixture of neopentane and n-pentane. The present work demonstrates that the method can be used for separating other mixtures of hydrocarbons as well, by attempting the separation of a mixture of 2,2-dimethyl butane and n-pentane. Intermolecular interaction potentials have been modified to reproduce the experimental heat of adsorption and diffusivity of 2,2-dimethyl butane and n-pentane in zeolite NaY. The method involves choosing the correct host zeolite or other porous solids and introducing hot zones at appropriate positions. This result drives both the components to the opposite ends of the zeolite column, thus leading to separation. The achieved separation factors are much higher than what can be obtained with the help of existing methods. Different properties have been computed to understand the process involved in the separation of the mixture. The approach employed here uses very little energy for separation, making it suitable for green chemistry.

Cost-effective, fast, and reliable DNA sequencing can be enabled by advances in nanopore-based methods, such as the use of atomically thin graphene membranes. However, strong interaction of DNA bases with graphene leads to undesirable effects such as sticking of DNA strands to the membrane surface. While surface functionalization is one way to counter this problem, here, we present another solution based on a heterostructure nanopore system, consisting of a monolayer of graphene and hexagonal boron nitride (hBN) each. Molecular dynamics studies of DNA translocation through this heterostructure nanopore revealed a surprising and crucial influence of the heterostructure layer order in controlling the base specific signal variability. Specifically, the heterostructure with graphene on top of hBN had nearly 3-10× lower signal variability than the one with hBN on top of graphene. Simulations point to the role of differential underside sticking of DNA bases as a possible reason for the observed influence of the layer order. Our studies can guide the development of experimental systems to study and exploit DNA translocation through two-dimensional heterostructure nanopores for single molecule sequencing and sensing applications.

The effective translocation of small interfering RNA (siRNA) across cell membranes has become one of the main challenges in gene silencing therapy. In this study, we have carried out molecular dynamics simulations to investigate a systematic procedure with different carriers that could be convenient for efficient siRNA delivery into the cell. Starting with poly-amido-amine (PAMAM) dendrimers and cholesterol molecules as carriers, we have found cholesterol as the most efficient carrier for siRNA when it is covalently attached with the siRNA terminal group. Our simulations show that binding of this complex in the lipid membrane alters the structure and dynamics of the nearby lipids to initiate the translocation process. Potential of mean force (PMF) was computed for siRNA with the carriers along the bilayer normal to understand the spontaneity of the process. Though all the PMF profiles show repulsive interaction inside the bilayer, the siRNA with cholesterol shows a comparative attractive interaction (∼27 kcal/mol) with respect to the siRNA-PAMAM complex. Altogether, our results demonstrate the binding interaction of the siRNA-carrier complex in the lipid membrane and propose a theoretical model for the efficient carrier by comparative study of the binding. The probable mechanism of the translocation process is also provided by the alteration of the lipid structure and dynamics for specifically siRNA-cholesterol binding.

Metastasis is the leading cause of cancer mortality. Throughout the cascade of metastasis, cancer cells are exposed to both chemical and mechanical cues which influence their migratory behavior and survival. Mechanical forces in the milieu of cancer may arise due to excessive growth of cells in a confinement as in case of solid tumors, interstitial flows within tumors and due to blood flow in the vasculature as in case of circulating tumor cells. The focus of this review is to highlight the mechanical forces prevalent in the cancer microenvironment and discuss the impact of mechanical stresses on cancer progression, with special focus on mechanically induced autophagic response in cancer cells. Autophagy is a cellular homeostatic mechanism that a cell employs not only for recycling of damaged organelles and turnover of proteins involved in cellular migration but also as an adaptive response to survive through unfavourable stresses. Elucidation of the role of mechanically triggered autophagic response may lead to a better understanding of the mechanobiological aspects of metastatic cancer and unravelling the associated signaling mechanochemical pathways may hint at potential therapeutic targets.

A metal-free, simultaneous triple C-C coupling cyclization reaction between phenacyl bromides and indoles is discovered in a highly regioselective fashion to furnish 3,5-diarylcarbazoles. DMAP is utilized as the only reagent for the unusual and rapid cyclization reaction to furnish all new carbazole compounds through installation of a great diversity of substituents. A plausible radical mechanism for the new reaction is predicted by conducting various control experiments, competitive reactions, furoindole formation, and ESI-MS analyses of the ongoing cyclization reaction.

The DNA molecule, apart from carrying the genetic information, plays a crucial role in a variety of biological processes and find applications in drug design, nanotechnology and nanoelectronics. The molecule undergoes significant structural transitions under the influence of forces due to physiological and non-physiological environments. Here, we summarize the insights gained from simulations and single-molecule experiments on the structural transitions and mechanics of DNA under force, as well as its elastic properties, in various environmental conditions, and discuss appealing future directions., Review Article, Accepted for publication in Current Opinion in Structural Biology

The inert nature of most commercial polymers and nanomaterials results in limitations of applications in various industrial fields. This can be solved by surface modifications to improve physicochemical and biological properties, such as adhesion, printability, wetting and biocompatibility. Polymer functionalization allows to graft specific moieties and conjugate molecules that improve material performances. In the last decades, several approaches have been designed in the industry and academia to graft functional groups on surfaces. Here, we review surface decoration of polymers and nanomaterials, with focus on major industrial applications in the medical field, textile industry, water treatment and food packaging. We discuss the advantages and challenges of polymer functionalization. More knowledge is needed on the biology behind cell–polymer interactions, nanosafety and manufacturing at the industrial scale.

Functionalizing graphene with polymers is an important area of research, owing to the potential applications of graphene in biomedicine and nanotechnology. In this paper, we investigate the covalen...

A new computational framework based on multiscale modeling approach is developed to calculate the current–voltage (V–I) characteristics of a double stranded DNA (dsDNA) attached between two gold el...

The use of polymers and nanomaterials has vastly grown for industrial and biomedical sectors during last years. Before any designation or selection of polymers and their nanocomposites, it is vital to recognize the targeted applications which require these platforms to be modified. Surface functionalization to introduce the desired type and quantity of reactive functional groups to target a cell or tissue in human body is a pivotal approach to improve the physicochemical and biological properties of these materials. Herein, advances in the functionalized polymer and nanomaterials surfaces are highlighted along with their applications in biomedical fields, e.g., antimicrobial therapy and drug delivery.

We have identified different N-substituted 2-pyridones as inbuilt directing groups for selective C–H-activated functionalization instead of deprotecting and/or throwing away the directing groups. A...

We contributed a new benzimidate chemistry through moisture-insensitive NiII/NiII-FeIII combo-catalysis for a simultaneous 2–3 bond-forming gem-diamidation and amidoindolyzation cascade reaction to...

The present review provides a comprehensive outlook toward the possibilities of developing a functional in vitro liver tissue model on a paper platform. To this end, we first addressed the suitabil...

The lack of optimal physiological properties, bacterial colonization, and auto-osteoinduction, are the foremost issues of orthopedic implantations. In terms of bone healing, many researchers have reported the release of additional growth factors of the implanted biomaterials to accelerate the bone regeneration process. However, the additional growth factor may cause side effects such as contagion, nerve pain, and the formation of ectopic bone. Thus, the design of an osteoconductive scaffold having excellent biocompatibility, appropriate physicomechanical properties, and promoted auto osteoinductivity with antibacterial activity is greatly desired. In this study, 2D rodlike nanohydroxyapatite (nHA) adorned titanium phosphate (TP) with a flowerlike morphology was synthesized by a hydrothermal precipitation reaction. The nanohybrid material (nHA-TP) was incorporated into the synthesized polycaprolactone diol and spermine based thermoplastic polyurethane-urea (PUU) via in situ technique followed by salt leaching to fabricate the macroporous 3D polymer nanohybrid scaffold (PUU/nHA-TP). Structure explication of PUU was performed by NMR spectroscopy. The synthesized nanohybrid scaffold with 1% nHA-TP showed 67% increase of tensile strength and 18% improved modulus compared to the pristine PUU via formation of H-bonding or dative bonds between the metal and the amide linkage of the polyurethane or polyurea. In vitro study showing improved cell viability and proliferation of the seeded cell revealed the superior osteoconductivity of the nanohybrid scaffold. Most importantly, the in vivo experiments revealed a significant amount of bone regeneration in the nanohybrid scaffold implanted tibial site compared to the pristine scaffold without any toxic effect. Introduction of the minute amount of titanium phosphate within the adorned nHA promotes the osteoconductivity significantly by the capability of forming coordinate bonds of the titanium ion. Depending on the mechanical, physicochemical, in vitro characteristics, and in vivo osteoconductivity, the PUU/nHA-TP nanohybrid scaffold has great potential as an alternative biomaterial in bone tissue regeneration application.

DNA has emerged as one of the smartest biopolymers to bridge the gap between chemical science and biology to design scaffolds like hydrogels by physical entanglement or chemical bonding with remarkable properties. We present here a completely new application of DNA-based hydrogels in terms of their capacity to stimulate membrane endocytosis, leading to enhanced cell spreading and invasion for cells in ex vivo 3D spheroids models. Multiscale simulation studies along with DLS data showed that the hydrogel formation was enhanced at lower temperature and it converts to liquid with increase in temperature. DNA hydrogels induced cell spreading as observed by the increase in cellular area by almost two-fold followed by an increase in the receptor expression, the endocytosis, and the 3D invasion potential of migrating cells. Our first results lay the foundation for upcoming diverse applications of hydrogels to probe and program various cellular and physiological processes that can have lasting applications in stem cell programming and regenerative therapeutics.

Quorum sensing, the microbial communication system, is gaining importance as a therapeutic target against pathogens. The two key reasons for the rising demand of quorum sensing (QS) inhibitory molecules are low selective pressure to develop resistance by pathogens and possibility of more species-specific effects. Due to complex interactions in a unique niche of live plant tissues, endophytes, as a survival mechanism, potentially produce various bioactive compounds such as QS inhibitors. We report the isolation of an endophytic fungus Kwoniella sp. PY016 from the medicinal plant "Bahera" (Terminalia bellirica), which exhibits substantial quorum sensing inhibition and anti-biofilm activities against the standard test organism, Chromobacterium violaceum. Sugar, sugar alcohol, carboxylic acid, lipid, and phenolic classes of metabolites (predominantly xylitol) are responsible components of the metabolome for the desired bioactivity. A judicious combination of single-factor-at-a-time strategy and artificial neural network modeling combined with genetic algorithm was employed for the selection and optimization of the critical process and medium parameters. Through this newly adopted hybrid model-based optimization, the quorum sensing inhibitory activity of the endophytic metabolome was increased by ~ 30%. This is the first report on optimization of QS inhibitory activity from any fungal endophyte using such a hybrid advanced approach.

Protein adsorption is the first key step in cell-material interaction. The initial phase of such adsorption process can only be probed using modelling approaches like molecular dynamics (MD) simulation. Despite a large number of studies on the adsorption behaviour of proteins on different biomaterials including hydroxyapatite (HA); little attention has been paid towards quantitative assessment of the effects of various physicochemical influencers like surface modification, pH, and ionic strength. Among these factors, surface modification through isomorphic substitution of foreign ions inside the apatite structure is of particular interest in the context of protein-HA interaction as it is widely used to tailor the biological response of HA. Given this background, we present here the molecular-level understanding of fibronectin (FN) adsorption mechanism and kinetics on Sr2+-doped HA (001) surface, at 300K by means of all-atom molecular dynamics simulation. Electrostatic interaction involved in adsorption of FN on HA was found to be significantly modified in presence of Sr2+ doping in apatite lattice. In harmony with the published experimental observations, the Sr-doped surface was found to better support FN adhesion compared to pure HA, with 10 mol% Sr-doped HA exhibiting best FN adsorption. Sr2+ ions also influence the stability of the secondary structure of FN, as observed from the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analysis. The presence of Sr2+ enhances the flexibility of specific residues (residue no. 20-44, 74-88) of the FN module. Rupture forces to disentangle FN from the biomaterials surface, obtained from steered molecular dynamics (SMD) simulations, were found to corroborate well with the results of equilibrium MD simulations. One particular observation is that, the availability of RGD motif for the interaction with cell surface receptor integrin is not significantly influenced by Sr2+ substitution. Summarizing, the present work establishes a quantitative foundation towards the molecular basis of the earlier experimentally validated better cytocompatibility of Sr-doped HA.

Some recent SARS-CoV-2 variants appear to have increased transmissibility than the original strain. An underlying mechanism could be the improved ability of the variants to bind receptors on target cells and infect them. In this study, we provide atomic-level insight into the binding of the receptor binding domain (RBD) of the wild-type SARS-CoV-2 spike protein and its single (N501Y), double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants to the human ACE2 receptor. Using extensive all-atom molecular dynamics simulations and advanced free energy calculations, we estimate the associated binding affinities and binding hotspots. We observe significant secondary structural changes in the RBD of the mutants, which lead to different binding affinities. We find higher binding affinities of the double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants than the wild type and the N501Y variant, which could contribute to the higher transmissibility of recent variants containing these mutations.

Diabetic Nephropathy (DN) is a debilitating consequence of both Type 1 and Type 2 diabetes affecting the kidney and renal tubules leading to End Stage Renal Disease (ESRD). As diabetes is a world epidemic and almost half of diabetic patients develop DN in their lifetime, a large group of people is affected. Due to the complex nature of the disease, current diagnosis and treatment are not adequate to halt disease progression or provide an effective cure. DN is now considered a manifestation of inflammation where inflammatory molecules regulate most of the renal physiology. Recent advances in genetics and genomic technology have identified numerous susceptibility genes that are associated with DN, many of which have inflammatory functions. Based on their role in DN, we will discuss the current aspects of developing biomarkers and molecular therapy for advancing precision medicine.

[Image: see text] Acute respiratory distress syndrome (ARDS) is one of the critical stages of COVID-19, leading to lung injury and hemolysis. Dysfunctional hemoglobin (Hb) suffers low-level oxygenation, overloaded iron, and down-regulation of hemeoxygenase-1 (HO-1), representing potential therapeutic interventions. This Viewpoint outlines the Hb–HO-1 system as a host-cell target, and proposes possible therapies, including iron chelation and CO therapies, against COVID-19 with ARDS.

Recent studies have shown that the utility of nanocarriers for the transportation of gaseous signalling molecules to their target site in a biological environment is an effective approach. In this work, we have developed for the first time visible light responsive nanocarriers for the effective release of H2S. Our newly developed nanocarriers for H2S release are constructed using two main ingredients: fluorescent carbon dots and quinoline as an H2S donor. The developed nanocarriers provided interesting properties like good solubility under physiological conditions, excellent fluorescence properties and efficient release ability of H2S with good quantum yield upon visible light irradiation. In vitro studies revealed that our designed nanocarriers exhibited abilities like efficient cellular internalization and good biocompatibility.

In this study, we compare the charge transport properties of multiple double-stranded (ds)RNA sequences with corresponding dsDNA sequences. Recent studies have presented a contradictory picture of relative charge transport efficiencies in A-form DNA : RNA hybrids and dsDNA. Using a multiscale modelling framework, we compute conductance of dsDNA and dsRNA using Landauer formalism in the coherent limit and Marcus-Hush theory in the incoherent limit. We find that dsDNA conducts better than dsRNA in both the charge transport regimes. Our analysis shows that the structural differences in the twist angle and slide of dsDNA and dsRNA are the main reasons behind the higher conductance of dsDNA in the incoherent hopping regime. In the coherent limit however, for the same base pair length, the conductance of dsRNA is higher than that of dsDNA for the morphologies where dsRNA has a smaller end-to-end length relative to that of dsDNA.

Herein, we report knitting of a thiophenyltriazine-based porous organic polymer (TTPOP) with high surface area and high abundance of nitrogen and sulfur sites, synthesized through a simple one-step Friedel–Crafts reaction of 2,4,6-tri(thiophen-2-yl)-1,3,5-triazine and formaldehyde dimethyl acetal in the presence of anhydrous FeCl3, and thereafter grafting of Cu(OAc)2·H2O in the porous polymer framework to achieve the potential catalyst (CuII-TTPOP). TTPOP and CuII-TTPOP were characterized thoroughly utilizing solid-state 13C-CP MAS NMR, Fourier transform infrared, wide-angle powder X-ray diffraction, thermogravimetric analysis, and X-ray photoelectron spectroscopy and surface imaging by transmission electron microscopy and field emission scanning electron microscopy. The porosity of the nanomaterials was observed in the surface imaging and verified through conducting N2 gas adsorption techniques. Keeping in mind the tremendous importance of C-C and C-N coupling and cyclization processes, the newly synthesized CuII-TTPOP was employed successfully for a wide range of organic catalytic transformations under mild conditions to afford directly valuable diindolylmethanes and spiro-analogues, phthalimidines, propargyl amines, and their sugar-based chiral compounds with high yields using readily available substrates. The highly stable new heterogeneous catalyst showed outstanding sustainability, robustness, simple separation, and recyclability.

A protein isolate was prepared from karanj seed (KPI) with 921.2 g protein/kg seed, which contained a negligible amount of anti‐nutritional factors and a balanced amino acid composition, especially rich in methionine. For 60‐day feeding trial, five isonitrogenous (300 g/kg CP) and isocaloric (15 MJ DE/kg) diets were formulated by replacing soybean protein isolate (SPI) on protein equivalent basis, KPI‐0 (control, 0 g/kg KPI); KPI‐25 (replacing 250 g/kg SPI protein with KPI); KPI‐50 (replacing 500 g/kg SPI protein with KPI); KPI‐75 (replacing 750 g/kg SPI protein with KPI) and KPI‐100 (replacing 1,000 g/kg SPI protein with KPI) for the feeding of L. rohita. The weight gain percentage, specific growth rate, feed conversion ratio and protein efficiency ratio were not significantly (p > .05) varied among the KPI fed and control groups. A significantly higher hepatosomatic index was recorded in the control and KPI‐25 groups compared with other groups. The whole‐body compositions, except ether extract, did not differ significantly (p > .05) among the groups. Digestive (amylase, protease, lipase and alkaline phosphatase) and metabolic enzyme activities (hexokinase, transaminases and lactate dehydrogenase) and glycogen stores were not significantly affected, whereas intestinal alkaline phosphatase differed significantly (p

A paradigm shift in conventional insulin delivery techniques is required to provide diabetic patients with painless, precise, safe and accurate insulin delivery solutions. Large size insulin molecules can be pushed through human skin layers by a micropump through hollow microneedles which provide a painless interphase to human skin. Ionic polymer metal composite membranes offer great advantages in micropump actuation due to their large deflections at relatively low actuation voltages. This makes them suitable to be implemented in insulin delivery devices. This article presents a novel integrated design of an insulin delivery device (IDD) consisting of a hollow microneedle array, drug reservoir and Nafion membrane actuation based micropump. To test the feasibility of the gold coated Nafion 115 membrane, it is utilized in the conventional circular as well as modified geometry having greater degree of freedom of movement by introducing cuts in membrane in a micropump structure and then implemented in the proposed IDD structure. The IDD achieves a DI water flowrate of $47.2~\mu $ L/min and Insulin flowrate of $44.8~\mu $ L/min for membrane with modified geometry which is higher as compared to the conventional membrane design. The device can achieve tunable insulin flowrate in the range of 20–45 $\mu $ L/min by varying the frequency (0.1-0.5Hz) and voltage (3-6V) paving way for its commercialization for painless insulin delivery. [2019-0109]

Unprecedented I2-catalyzed α,α-C(sp3)-H, decarboxylative α-C(sp3)-H, lactonized α-C(sp3)-H, and α,β-C(sp3)-H functionalized 5- and 6-annulation as well as α-C(sp3)-H activated 6-lactonization of primary aliphatic amines are devised under aerobic conditions. The metal-free sustainable strategy was employed for the diverse construction of valuable five-and six-membered polycyclic N,O-heteroaromatics such as oxazoles, 1,4-oxazines, and oxazin-2-one with a rapid reaction rate and high yield. The viability of this mild nonmetallic catalysis is successfully verified through syntheses of labile chiral heterocyclic analogues. In contrast to the common practice, this method is not limited to use of prefunctionalized amines, directing groups (DGs) and/or transient DGs, metal catalysts, and traditional oxidants. The possible mechanistic pathway of the annulation reaction is investigated by control experiments and ESI-MS data collected for a reaction mixture of the ongoing reaction. The synthesized new compounds are potent organic nanobuilding blocks to achieve valuable organic nanomaterials of different sizes, shapes, and dimensions, which are under investigation for the discovery of high-tech devices of innovative organic nanoelectronics and photophysical properties.

The present study delineates the preparation, characterization, and application of (3-Aminopropyl)triethoxysilane (APTES)/Caprine liver-derived extracellular matrix (CLECM) coated paper matrix for cell delivery. Here, we exploited positively charged surface of the paper matrix (as imparted by APTES derivatization) to improve the biological responses of the cells. Our results demonstrated that the functionalized paper matrixes favored the adhesion, growth, and proliferation of multiple cell types including normal, transformed, cancerous, and stem cells as compared to the pristine paper matrix. Upon implantation into the mice model, the developed paper matrix supported infiltration of the host cells and vasculature without showing any evidence of significant systemic toxicity. Moreover, the cells cultured on the paper matrix, when delivered to the CAM and mouse models, showed an enhanced vascular network around the substrate, thereby confirming its potential to deliver the cells in vivo. Together, the study confirms that the reported paper-based platform is easy to fabricate, cheap, portable and could efficiently be applied to cell delivery applications for either tissue repair or the development of humanized animal model.

This study aimed to identify the intracellular binding partner of a unique class of staphylococcal secreted exotoxins called superantigen-like proteins (SSL) from human macrophage and keratinocyte cell lysates. Here, we report that SSL1 specifically binds to human extracellular signal-regulated kinase 2 (hERK2), an important stress-activated kinase in mitogen-activated protein kinase signaling pathways. Western blot and in vitro binding studies with recombinant hERK2 confirmed the binding interaction of SSL1, SSL7, and SSL10 with hERK2. Moreover, the SSLs-hERK2 interaction was validated biochemically by ELISA. Our finding shows that SSLs play a novel role by binding with host cell MAP kinase signaling pathway protein. Understanding the SSL-hERK2 interaction will also provide a basis for designing SSL-based peptide inhibitors of hERK2 in cancer therapy.

The Nb-EISA catalyst with relatively low Nb loadings (∼2 wt %) shows exceptional propylene epoxidation performance with H2O2 as oxidant at 30–40 °C, 5–9 bar propylene pressure with nearly total pro...

Persulfides have been considered as potential signaling compounds similar to the H2S in "S-persulfidation", a sulfur-mediated redox cycle. The research of this sulfur-mediated species is hindered because of the lack of efficient persulfide donors. In this current study, we have developed one- and two-photon-activated persulfide donors based on an o-nitrobenzyl (ONB) phototrigger, which releases the biologically active persulfide (N-acetyl l-cysteine persulfide, NAC-SSH) in a spatiotemporal manner. Next, we have demonstrated the detection of persulfide release both qualitatively and quantitatively using the well-known "turn on" fluorescence probe, that is, monobromobimane, and the trapping agent, that is, 2,4-dinitrofluorobenzene, respectively. Furthermore, we examined the cytotoxicity of synthesized persulfide donors on HeLa cells and the cytoprotective ability in the highly oxidizing cellular environment.

The glycoproteins on the surface of human immunodeficiency virus (HIV) undergoes cascade of conformational transitions to evade the human immune system. The virus replicates inside the host and infects the T-cells instigating acquired immunodeficiency syndrome (AIDS). The glycoprotein 41 (gp41) of HIV helps to mediate the fusion of virus and host membranes. The detailed mechanism of host cell invasion by virus remains obscure due to the unavailability of experimental structure of complete gp41. In the current study, the post-fusion (PoF) trimeric structure of ecto-domain including transmembrane domain of gp41 was modeled using multiple homologous templates of Simian immunodeficiency virus (SIV) and HIV-1. In order to validate the gp41 model, interactions of three peptide inhibitors: T20, C37 and C34; were studied using all-atom molecular dynamics (MD) simulations, binding free-energy calculation and per-residue energy decomposition analysis. The binding free energy calculated using MM-PBSA (Molecular Mechanics Poisson-Boltzmann surface area) method predicts maximum affinity for C34 and minimum by T20 for gp41, which is in good agreement with the available computational and experimental studies. The van der Waals interaction is a dominant contributor for the peptide-gp41 complexes. The per-residue decomposition of energy confirmed the role of Trp117, Trp120 and Ile124, present in C34 and C37, for the strong hydrophobic interactions with the deep pocket localized around the N-terminal of gp41, which is lacking in T20. The HIV-1 gp41 structure developed in this work can be used in future study to gain insight into the mechanism of virus invasion and probing potent inhibitor to eliminate AIDS. Communicated by Ramaswamy H. Sarma

The synthetic chemists always look for developing new catalysts, sustainable catalysis, and their applications in various organic transformations. Herein, we report a new class of water-soluble complexes, (Ar-tpy)RuII(ACN)3, utilizing designed terpyridines possessing electron-donating and -withdrawing aromatic residues for tuning the catalytic activity of the Ru(II) complex. These complexes displayed excellent catalytic activity for several oxidative organic transformations including late-stage C-H functionalization of aldehydes with NH2OR to valuable primary amides in nonconventional aqueous media with excellent yield. Its diverse catalytic power was established for direct oxo-scissoring of a wide range of alkenes to furnish aldehydes and/or ketones in high yield using a low catalyst loading in the water. Its smart catalytic activity under mild conditions was validated for dioxygenation of alkynes to highly demanding labile synthons, 1,2-diketones, and/or acids. This general and sustainable catalysis was successfully employed on sugar-based substrates to obtain the chiral amides, aldehydes, and labile 1,2-diketones. The catalyst is recovered and reused with a moderate turnover. The proposed mechanistic pathway is supported by isolation of the intermediates and their characterization. This multifaceted sustainable catalysis is a unique tool, especially for late-stage functionalization, to furnish the targeted compounds through frequently used amidation and oxygenation processes in the academia and industry.

Fluorescent chemosensors with aggregation induced emission enhancement (AIEE) emerge as promising tools in the field of sensing materials. Herein, we report the design, synthesis and applicability of a Schiff base chemosensor 1-(benzo[1,3]dioxol-4-ylmethylene-hydrazonomethyl)-naphthalen-2-ol (Hbdhn) of AIE characteristics that exhibits highly effective and selective response towards Zn2+ . The sensing effect of Hbdhn was evaluated by means of absorption/emission spectra and corresponding underlying photophysical mechanisms were proposed based on extensive quantum-chemical (TD)DFT calculations. The aggregated states in different DMSO/H2 O ratios and in a presence of Zn2+ were examined by fluorescence lifetime measurements, dynamic light scattering and scanning electron microscopy studies. The bioimaging abilities of Hbdhn were evaluated for Zn2+ in HepG2 cancer cells. The results demonstrate instant, stable in time and reproducible, colorimetric turn-on response with superb selectivity and sensitivity of Hbdhn towards Zn2+ , based on chelation enhanced fluorescence mechanism. AIEE improves further Hbdhn properties, leading to strong, long-lived fluorescence, with appearance of rod-like particles, in 90 % of water in DMSO and only 10 % of water in DMSO in the presence of Zn2+ . All these features combined with successful biomaging studies make Hbdhn one of the most promising candidate for practical applications among recently proposed related systems.

The development of a pre-vascularized liver tissue construct with native-like 3-dimensional (3D) microarchitecture and extracellular matrix (ECM) composition is essential to meet the current demand for liver transplantation. Here, we report the methodology and in-depth characterization of the decellularized caprine liver scaffold (CLECM-S) for tissue engineering application. CLECM-S retained crucial ECM components and structural features similar to the native liver tissue. For comparative evaluation, conventional glutaraldehyde crosslinked collagen scaffold (Col-S) was taken as a control. CLECM-S underwent a slow but sustained swelling and collagenase mediated degradation and had the mechanical stiffness closer to that of the native human liver. HepG2 cells cultured on CLECM-S exhibited an enhanced expression of mature and functional hepatocyte markers. In addition, CLECM-S also showed pro-angiogenic properties as confirmed by Chick Chorioallantoic Membrane (CAM) assay. Upon implantation in a mouse model, the scaffolds did not elicit any significant immunogenic response. These results, together, provide a solid evidence depicting superiority of CLECM-S over conventional Col-S for liver tissue engineering applications.

Current study focusses on the concomitant production of fatty acid methyl ester (FAME, biodiesel) and exopolysaccharides (EPS) from Scenedesmus abundans cell factory in flat panel photobioreactor using cost effective harvesting strategy. Parallel mini and medium scale flat panel photobioreactors (PBRs) with special gas sparging system enabling high gas to liquid mass transfer and efficient mixing were designed. Biomass titer of 6.9 g/l with overall biomass productivity of 1.2 g/l/day was achieved with constant high light intensity of 2162 µE/m2/s in growth phase (134 h) using optimum nutrient concentration. FAME concentration of 1.53 g/l was achieved after 15 days of nitrogen deprivation condition with productivity of 67 mg/l/day. The EPS production of 236 mg/l with a yield of 37 mg/g biomass was achieved. The strain proved its capability to produce multiproducts simultaneously in a single stage PBR by natural autoflocculation harvesting technology.

We report the enhancement of the structural stability of a DNA nanotube (DNT) by changing the salt concentrations for three different salt species, namely, NaCl, KCl, and MgCl2. Using fully atomist...

Production of cellulase enzyme by Trichoderma reesei using cheap lignocellulosic material sugarcane bagasse was studied. Enzyme production from lignocellulosic biomass required pretreatment to decrease the cellulose crystallinity where inhibitors are released in hydrolysate. Strategies for solid bagasse feeding and pH shifting during fermentation have been developed for cellulase production enhancement by T. reesei NCIM 1186. To improve the cellulase production along with xylose utilization from the hydrolysate various feeding approach of pretreated solid bagasse in liquid hydrolysate grown culture has been investigated. This T. reesei has shown the capability of complete consumption of acetic acid, furfural, 5-hydroxymethyl, furfural and formic acid along with enzyme production. The maximum cellulase production of 1.5 U/ml CMCase and 1.01 U/ml FPase was obtained using a solid bagasse strategy developed here where T. reesei was grown in sugar rich hydrolysate followed by early feeding of pretreated solid bagasse along with pH shifting strategy in a stirred tank bioreactor. This production was almost fivefolds increment of both FPase and CMCase compared to culture grown in whole slurry mixture.

The nitration of tyrosine residues in proteins represents a specific footprint of the formation of reactive nitrogen species (RNS) in vivo. Here, the fusion product of orange protein (ATCUN-ORP) was used as an in vitro model system containing an amino terminal Cu(II)- and Ni(II)-binding motif (ATCUN) tag at the N-terminus and a native tyrosine residue in the metal-cofactor-binding region for the formation of 3-NO2 -Tyr (3-NT). It is shown that NiII -ATCUN unusually performs nitration of tyrosine at physiological pH in the presence of the NO2- /SO32- /O2 system, which is revealed by a characteristic absorbance band at 430 nm in basic medium and 350 nm in acidic medium (fingerprint of 3-NT). Kinetics studies showed that the formation of 3-NT depends on sulfite concentration over nitrite concentration suggesting key intermediate products, identified as oxysulfur radicals, which are detected by spin-trap EPR study by using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). This study describes a new route in the formation of 3-NT, which is proposed to be linked with the sulfur metabolism pathway associated with the progression of disease occurrence in vivo.

Intrauterine Contraceptive Devices with multifaceted application potential is a need of an hour. Although, copper-based IUDs exert an effective contraceptive as well as anticancer effects in a long-term basis, but also results in multiple complications. In this regard, RISUG® a polymer based contraceptive device has been introduced as a suitable alternative. However, its potential to impart protective effects against development of endometrial cancer still remains unexplored. This article presents the hypothesis on this unexplored domain and provides scientific facts to support the hypothesis. The mechanism of anticancerous activity is hypothesized that RISUG® involves its lipid membrane destabilizing activity. This activity is modulated by both, the cellular microenvironment and lipid bilayer composition. Acidic environment along with the significantly higher fluidic nature of lipid bilayer of the cancerous cells make them more prone to lipid solubilisation effect of RISUG®. We here present an in-depth insight into the factors that would favour faster solubilisation of cancer cell membrane, thereby exerting an anticancer effect.

We have elucidated the role of unsaturated fatty acid in the in vitro model phospholipid membrane and in vivo live cell membrane. Fluorescence microscopy and time-resolved fluorescence spectroscopy have been employed to uncover how modulation of vesicle bilayer fluidity persuades structural transformation. This unsaturation induced structural transformation due to packing disorder in bilayer has been delineated through spatially resolved fluorescence lifetime imaging microscopy (FLIM) and fluorescence polarization or anisotropy imaging microscopy (FPIM/FAIM). Structure-function relationship of phospholipid vesicle is also investigated by monitoring intervesicular water dynamics behavior, which has been demonstrated by temporally resolved fluorescence spectroscopy (TRFS) techniques. Nevertheless, it has also been manifested from this study that loss of rigidity in bilayer breaks down the strong hydrogen bond (H-bond) network around the charged lipid head groups. The disruption of this H-bond network increases the bilayer elasticity, which helps to evolve various kinds of vesicular structure. Furthermore, the significant influence of unsaturated fatty acid on membrane bilayer has been ratified through in vivo live cell imaging.

Background Epithelial-to-mesenchymal transition (EMT), a key step in oral cancer progression, is associated with invasion, metastasis, and therapy resistance, thus targeting the EMT represents a critical therapeutic strategy for the treatment of oral cancer metastasis. Our previous study showed that Abrus agglutinin (AGG), a plant lectin, induces both intrinsic and extrinsic apoptosis to activate the tumor inhibitory mechanism. Objective This study aimed to investigate the role of AGG in modulating invasiveness and stemness through EMT inhibition for the development of antineoplastic agents against oral cancer. Methods The EMT- and stemness-related proteins were studied in oral cancer cells using Western blot analysis and fluorescence microscopy. The potential mechanisms of Snail downregulation through p73 activation in FaDu cells were evaluated using Western blot analysis, immunoprecipitation, confocal microscopy, and molecular docking analysis. Immunohistochemical staining of the tumor samples of AGG-treated FaDu-xenografted nude mice was performed. Results At the molecular level, AGG-induced p73 suppressed Snail expression, leading to EMT inhibition in FaDu cells. Notably, AGG promoted the translocation of Snail from the nucleus to the cytoplasm in FaDu cells and triggered its degradation through ubiquitination. In this setting, AGG inhibited the interaction between Snail and p73 in FaDu cells, resulting in p73 activation and EMT inhibition. Moreover, in epidermal growth factor (EGF)-stimulated FaDu cells, AGG abolished the upregulation of extracellular signal-regulated kinase (ERK)1/2 that plays a pivotal role in the upregulation of Snail to regulate the EMT phenotypes. In immunohistochemistry analysis, FaDu xenografts from AGG-treated mice showed decreased expression of Snail, SOX2, and vimentin and increased expression of p73 and E-cadherin compared with the control group, confirming EMT inhibition as part of its anticancer efficacy against oral cancer. Conclusion In summary, AGG stimulates p73 in restricting EGF-induced EMT, invasiveness, and stemness by inhibiting the ERK/Snail pathway to facilitate the development of alternative therapeutics for oral cancer.

DNA has emerged as one of the smartest biopolymers to bridge the gap between chemical science and biology to design scaffolds like hydrogels by physical entanglement or chemical bonding with remarkable properties. We present here a completely new application of DNA based hydrogels in terms of their capacity to stimulate membrane endocytosis, leading to enhanced cell spreading and invasion for cells in ex-vivo 3D spheroids models. Multiscale simulation studies along with DLS data showed that the hydrogel formation was enhanced at lower temperature and it converts to liquid with increase in temperature. DNA hydrogels induced cell spreading as observed by increase in cellular area by almost two-folds followed by increase in receptor expression, endocytosis and 3D invasion potential of migrating cells. Our first results lay the foundation for upcoming diverse applications of hydrogels to probe and program various cellular and physiological processes that can have lasting applications in stem cells programming and regenerative therapeutics.