Endophytic bacilli from Cyamopsis tetragonoloba (L.) Taub. induces plant growth and drought tolerance.

Cyamopsis tetragonoloba (L.) Taub. (guar) is a commercially important crop known for its galactomannan content in seeds. Drought stress is a significant global concern that compromises the productivity of major legumes including guar. The endophytic microbes associated with plants play a significant role in enhancing plant growth and modulating the impact of abiotic stress(s). The present study involved the isolation of 73 endophytic bacteria from the guar seeds of drought-tolerant (RGC-1002 and RGC-1066) and sensitive (Sarada and Varsha) varieties. Based on multiple PGP attributes and drought tolerance, at 50% PEG6000 w/v, 11 efficient isolates were selected and identified through 16S rRNA gene sequencing. Isolates belonging to ten different species of bacilli including Cytobacillus oceanisediminis, Mesobacillus fermenti, Peribacillus simplex from sensitive and Bacillus zanthoxyli, B. safensis, B. velezensis, B. altitudinis, B. licheniformis, B. tequilensis, and B. paralicheniformis isolated from tolerant varieties. A greenhouse experiment with a drought-sensitive guar variety demonstrated that inoculation of selected isolates showed comparatively better plant growth, higher relative water content (RWC), decreased carbon isotope discrimination ratio (Δ13C), increased chlorophyll, carotenoids, anthocyanin, and proline content, decreased malondialdehyde (MDA) and modulated defense enzymes as compared to their uninoculated controls. Tolerant variety isolates B. tequilensis NBRI14G and B. safensis NBRI10R showed the most promising results in improving plant growth and also drought stress tolerance in guar plants. This study represents for the first time that seed endophytic bacterial strains from guar can be utilized to develop the formulation for improving the productivity of guar under drought-stress conditions.

Orange peel-derived Cu2O/RGO nanocomposite: Mesoporous binary system for degradation of doxycycline in water.

In recent times, there is a mammoth challenge for the world and mankind to deal with the frequent use and misuse of antibiotics and its casual discard to the water bodies. The scavenging degradation of antibiotics which are no longer in use from the environment is a growing concern and compulsively needs to be addressed. Herein, we have devised a novel and green protocol for the synthesis of Cu2O decorated on reduced graphene oxide (Cu2O/RGO) nanocomposite (NCs) using agro-waste, i.e., orange pomace extract (OPE) as a reducing and stabilizing agent for the degradation of antibiotic. The biogenically synthesized Cu2O/RGO NCs proved to emerge as an excellent degradation catalyst exhibiting efficiency of 98.68% within 15 min and 86.38% within 30 min for 10 mg/L DC concentration assisted by ultrasound waves and solar light respectively in separate reactions. The complete degradation process followed a pseudo-first-order kinetics with a rate constant of 0.29 min- 1 and 0.0542 min- 1 for sonocatalytic and photocatalytic degradation process, respectively. Surface area analysis showed that with the increase in the GO amount, the doxycycline degradation increases. An in-depth mechanistic account of sonocatalytic and photocatalytic process has been discussed followed by a radical scavenging test which validated the major role of the synthesized NCs in the degradation of DC. The extraordinary catalytic indulgence of biogenically synthesized graphene-based nanocatalyst opens newer avenues for future research in green chemistry and catalytic field. Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-022-02895-2.

Rlip depletion prevents spontaneous neoplasia in TP53 null mice.

TP53 (p53) is a tumor suppressor whose functions are lost or altered in most malignancies. p53 homozygous knockout (p53-/-) mice uniformly die of spontaneous malignancy, typically T-cell lymphoma. RALBP1 (RLIP76, Rlip) is a stress-protective, mercapturic acid pathway transporter protein that also functions as a Ral effector involved in clathrin-dependent endocytosis. In stark contrast to p53-/- mice, Rlip-/- mice are highly resistant to carcinogenesis. We report here that partial Rlip deficiency induced by weekly administration of an Rlip-specific phosphorothioate antisense oligonucleotide, R508, strongly inhibited spontaneous as well as benzo(a)pyrene-induced carcinogenesis in p53-/- mice. This treatment effectively prevented large-scale methylomic and transcriptomic abnormalities suggestive of inflammation found in cancer-bearing p53-/- mice. The remarkable efficiency with which Rlip deficiency suppresses spontaneous malignancy in p53-/- mice has not been observed with any previously reported pharmacologic or genetic intervention. These findings are supported by cross-breeding experiments demonstrating that hemizygous Rlip deficiency also reduces the spontaneous malignancy phenotype of p53+/- mice. Rlip is found on the cell surface, and antibodies directed against Rlip were found to inhibit growth and promote apoptosis of cell lines as effectively as Rlip siRNA. The work presented here investigates several features, including oxidative DNA damage of the Rlip-p53 association in malignant transformation, and offers a paradigm for the mechanisms of tumor suppression by p53 and the prospects of suppressing spontaneous malignancy in hereditary cancer syndromes such as Li-Fraumeni.

Transport of hydrated nitrate and nitrite ions through graphene nanopores in aqueous medium.

Nitrate ( NO 3 - ) and nitrite ( NO 2 - ) ions are naturally occurring inorganic ions that are part of the nitrogen cycle. High doses of these ions in drinking water impose a potential risk to public health. In this work, molecular dynamics simulations are carried out to study the passage of nitrate and nitrite ions from water through graphene nanosheets (GNS) with hydrogen-functionalized narrow pores in presence of an external electric field. The passage of ions through the pores is investigated through calculations of ion flux, and the results are analyzed through calculations of various structural and thermodynamic properties such as the density of ions and water, ion-water radial distribution functions, two-dimensional density distribution functions, and the potentials of mean force of the ions. Current simulations show that the nitrite ions can pass more in numbers than the nitrate ions in a given time through GNS hydrogen-functionalized pore of different geometry. It is found that the nitrite ions can permeate faster than the nitrate ions despite the former having higher hydration energy in the bulk. This can be explained in terms of the competition between the number density of the ions along the pore axis and the free energy barrier calculated from the potential of mean force. Also, an externally applied electric field is found to be important for faster permeation of the nitrite over the nitrate ions. The current study suggests that graphene nanosheets with carefully created pores can be effective in achieving selective passage of ions from aqueous solutions.

Large scale and linear scaling DFT with the CONQUEST code.

We survey the underlying theory behind the large-scale and linear scaling density functional theory code, conquest, which shows excellent parallel scaling and can be applied to thousands of atoms with diagonalization and millions of atoms with linear scaling. We give details of the representation of the density matrix and the approach to finding the electronic ground state and discuss the implementation of molecular dynamics with linear scaling. We give an overview of the performance of the code, focusing in particular on the parallel scaling, and provide examples of recent developments and applications.

SMC1A is associated with radioresistance in prostate cancer and acts by regulating epithelial-mesenchymal transition and cancer stem-like properties.

Prostate cancer is one of the most commonly diagnosed cancers and a pressing health challenge in men worldwide. Radiation therapy (RT) is widely considered a standard therapy for advanced as well as localized prostate cancer. Although this primary therapy is associated with high cancer control rates, up to one-third of patients undergoing radiation therapy becomes radio-resistant and/or has tumor-relapse/recurrence. Therefore, focus on new molecular targets and pathways is essential to develop novel radio-sensitizing agents for the effective and safe treatment of prostate cancer. Here, we describe functional studies that were performed to investigate the role of structural maintenance of chromosome-1 (SMC1A) in radioresistance of metastatic prostate cancer cells. Short hairpin RNA (shRNA) was used to suppress SMC1A in metastatic castration-resistant prostate cancer cells, DU145 and PC3. Clonogenic survival assays, Western blot, RT-PCR, and γ-H2AX staining were used to assess the effect of SMC1A knockdown on radiation sensitivity of these prostate cancer cells. We demonstrate that SMC1A is overexpressed in human prostate tumors compared to the normal adjacent tissue. SMC1A knockdown limits the clonogenic potential, epithelial-mesenchymal transition (EMT), and cancer stem-like cell (CSC) properties of DU145 and PC3 cells and enhanced efficacy of RT in these cells. Targeted inhibition of SMC1A not only plays a critical role in overcoming radio-resistance in prostate cancer cells, but also suppresses self-renewal and the tumor-propagating potential of x-irradiated cancer cells. We propose that SMC1A could be a potential molecular target for the development of novel radio-sensitizing therapeutic agents for management of radio-resistant metastatic prostate cancer.

Nickel Selenide Nanoparticles as a Cheap Alternative for Pt-Counter Electrode in Dye-Sensitized Solar Cells.

Colloidal nickel selenide nanocrystals (NCs) of two different compositions i.e., Ni3Se2 and Ni3Se4, where one is Ni-rich while another is Se-rich are synthesized using the hot injection method by merely changing the injection and growth temperature while keeping the rest of the reaction conditions like solvent, ligands, amount of precursors and reaction time identical. These nanocrystals exhibit electrocatalytic activity in the reduction of triiodide (I-3) to iodide (3I-), therefore employed as counter electrodes (CE) in dye-sensitized solar cells (DSCs). The DSC based on nickel selenides displays an efficiency of 6.4%, comparable to the Pt-based cells prepared by us.

Preferential solvation, ion pairing, and dynamics of concentrated aqueous solutions of divalent metal nitrate salts.

We have investigated the characteristics of preferential solvation of ions, structure of solvation shells, ion pairing, and dynamics of aqueous solutions of divalent alkaline-earth metal nitrate salts at varying concentration by means of molecular dynamics simulations. Hydration shell structures and the extent of preferential solvation of the metal and nitrate ions in the solutions are investigated through calculations of radial distribution functions, tetrahedral ordering, and also spatial distribution functions. The Mg2+ ions are found to form solvent separated ion-pairs while the Ca2+ and Sr2+ ions form contact ion pairs with the nitrate ions. These findings are further corroborated by excess coordination numbers calculated through Kirkwood-Buff G factors for different ion-ion and ion-water pairs. The ion-pairing propensity is found to be in the order of Mg(NO3)2 < Ca(NO3)2 < Sr(NO3)2, and it follows the trend given by experimental activity coefficients. It is found that proper modeling of these solutions requires the inclusion of electronic polarization of the ions which is achieved in the current study through electronic continuum correction force fields. A detailed analysis of the effects of ion-pairs on the structure and dynamics of water around the hydrated ions is done through classification of water into different subspecies based on their locations around the cations or anions only or bridged between them. We have looked at the diffusion coefficients, relaxation of orientational correlation functions, and also the residence times of different subspecies of water to explore the dynamics of water in different structural environments in the solutions. The current results show that the water molecules are incorporated into fairly well-structured hydration shells of the ions, thus decreasing the single-particle diffusivities and increasing the orientational relaxation times of water with an increase in salt concentration. The different structural motifs also lead to the presence of substantial dynamical heterogeneity in these solutions of strongly interacting ions. The current study helps us to understand the molecular details of hydration structure, ion pairing, and dynamics of water in the solvation shells and also of ion diffusion in aqueous solutions of divalent metal nitrate salts.

CAD/CAM-Assisted Auricular Prosthesis Fabrication for a Quick, Precise, and More Retentive Outcome: A Clinical Report.

Auricular defects comprise a large proportion of maxillofacial deformities. Most patients with acquired deformities have psychosocial ineptness and seek cosmetic rehabilitation. Although minor defects can be corrected surgically, extensive deformities are difficult to reconstruct with plastic surgery. Contrary to that, prosthetic restoration can provide excellent esthetic results. The conventional methods of maxillofacial prosthesis fabrication are time consuming and the outcome depends on the technician's skill. The advent of CAD/CAM technology in the field of dentistry has brought enormous improvement in the quality of health care provided. In the past decade, several methods have been described employing CAD/CAM techniques for the cosmetic rehabilitation of auricular defects. This clinical report details the integration of multiple digital technologies of CT scanning, computer aided design, and rapid prototyping to construct an ear prosthesis with limited number of appointments.

Thickness-Dependent Charge Carrier Dynamics in CdSe/ZnSe/CdS Core/Barrier/Shell Nanoheterostructures.

We report the synthesis of CdSe/ZnSe/CdS heterostructures composed of type I and type II band alignments, where ZnSe acts as a barrier for charge carriers between the CdSe core and the CdS shell as well as being an active component of the type I (CdSe/ZnSe) and type II (ZnSe/CdS) structure simultaneously. We investigated the effect of the thickness of the barrier and the shell on the charge carrier dynamics by using UV/Vis absorbance, photoluminescence (PL), and time-resolved fluorescence techniques. The experimental data are supported by simple theoretical calculations based on effective mass approximation (EMA). PL results indicate the emission from both type I and type II structures. Time-resolved fluorescence studies show that the lifetime of the core emission decreases with increasing barrier width, owing to a greater confinement of the exciton to the core, whereas it increases with shell width because of the tunneling of charge carriers, primarily electrons, delaying the recombination of the exciton. The lifetime of the shell emission decreases with shell width as well as barrier width and height, with a larger effect being observed for the barrier width and negligible for the associated changes in the barrier height.

Lens specific RLIP76 transgenic mice show a phenotype similar to microphthalmia.

RALBP1/RLIP76 is a ubiquitously expressed protein, involved in promotion and regulation of functions initiated by Ral and R-Ras small GTPases. Presence of multiple domains in its structure enables RLIP76 to be involved in a number of physiological processes such as endocytosis, exocytosis, mitochondrial fission, actin cytoskeleton remodeling, and transport of exogenous and endogenous toxicants. Previously, we have established that RLIP76 provides protection to ocular tissues against oxidative stress by transporting the glutathione-conjugates of the toxic, electrophilic products of lipid peroxidation generated during oxidative stress. Therefore, we developed lens specific RLIP76 transgenic mice (lensRLIP76 Tg) to elucidate the role of RLIP76 in protection against oxidative stress, but these transgenic mice showed impaired lens development and a phenotype with small eyes similar to that observed in microphthalmia. These findings prompted us to investigate the mechanisms via which RLIP76 affects lens and eye development. In the present study, we report engineering of lensRLIP76 Tg mice, characterization of the associated phenotype, and the possible molecular mechanisms that lead to the impaired development of eye and lens in these mice. The results of microarray array analysis indicate that the genes involved in pathways for G-Protein signaling, actin cytoskeleton reorganization, endocytosis, and apoptosis are affected in these transgenic mice. The expression of transcription factors, Pax6, Hsf1, and Hsf4b known to be involved in lens development is down regulated in the lens of these Tg mice. However, the expression of heat shock proteins (Hsps), the downstream targets of Hsfs, is differentially affected in the lens showing down regulation of Hsp27, Hsp40, up regulation of Hsp60, and no effect on Hsp70 and Hsp90 expression. The disruption in the organization of actin cytoskeleton of these Tg mice was associated with the inhibition of the activation of Cdc42 and down regulation of cofilin phosphorylation. These mice may provide useful animal model for elucidating the mechanisms of lens development, and etiology of microphthalmia.

Effect of vinpocetine alone and in combination with enalapril in experimental model of diabetic cardiomyopathy in rats: possible involvement of PDE-1/TGF-ß/ Smad 2/3 signalling pathways.

OBJECTIVE: Diabetic cardiomyopathy (DC) is one of the severe secondary complications of diabetes mellitus in humans. Vinpocetine is an alkaloid having pleiotropic pharmacological effects. The present study is designed to investigate the effect of vinpocetine in DC in rats. METHODS: Rats were fed a high-fat diet for nine weeks along with single dose of streptozotocin after the second week to induce DC. The haemodynamic evaluation was performed to assess the functional status of rats using the Biopac system. Cardiac echocardiography, biochemical, oxidative stress parameters and inflammatory cytokine level were analysed in addition to haematoxylin-eosin and Masson's trichome staining to study histological changes, cardiomyocyte diameter and fibrosis, respectively. Phosphodiesterase-1 (PDE-1), transforming growth factor-ß (TGF-ß) and p-Smad 2/3 expression in cardiac tissues were quantified using western blot/RT-PCR. KEY FINDING: Vinpocetine treatment and its combination with enalapril decreased the glucose levels compared to diabetic rats. Vinpocetine improved the echocardiographic parameters and cardiac functional status of rats. Vinpocetine decreased the cardiac biochemical parameters, oxidative stress, inflammatory cytokine levels, cardiomyocyte diameter and fibrosis in rats. Interestingly, expressions of PDE-1, TGF-ß and p-Smad 2/3 were ameliorated by vinpocetine alone and in combination with enalapril. CONCLUSIONS: Vinpocetine is a well-known inhibitor of PDE-1 and the protective effect of vinpocetine in DC is exerted by inhibition of PDE-1 and subsequent inhibition of the expression of TGF-ß/Smad 2/3.

Renal Outcomes of Pregnancy-Related Acute Kidney Injury: a Single Centre Experience in India.

Objective:This study aimed to investigate the incidence, clinical characteristics, and outcomes of acute kidney injury (AKI) during pregnancy in Indian population. Materials and methods:A prospective observational study was conducted in pregnant patients admitted to Pt. B.D. Sharma PGIMS, Rohtak, Haryana, India. Acute kidney injury was assessed using Risk, Injury, Failure, Loss of function, and End-stage renal disease (RIFLE) criteria. Patients were analyzed on the basis of demographic data, detailed history, clinical examination, and laboratory investigations. The primary outcome was maternal renal outcome, including return to normal renal function and progression to chronic kidney disease (CKD). The secondary outcomes included the mode of delivery, complications of pregnancy, intensive care unit (ICU) admission, and maternal death. Results:A total of 51 patients with an average age of 29.5 years were included in the present study. About 49.9% of subjects had severe anemia and 41.2% were primigravida. The main cause of AKI was pre-eclampsia and postpartum hemorrhage. There was a marked improvement in renal outcome with 33 patients having complete renal recovery and six patients developed CKD was observed during three months follow-up period. The peaked median value of blood urea was 62.0 mg% in patients with normal renal function, 178.5 mg% in those with CKD and 120.0 mg% in expired patients (P=0.001). A statistically significant change in serum potassium (P=0.010) and creatinine levels (P<0.001) was observed during the follow-up period. Liver enzymes, including serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase, were high in all patients at the time of admission, but decreased to normal on follow-up. Conclusion:Our study indicates that pregnancy-related AKI patients present with multiorgan complications and many of them require mechanical ventilation and renal replacement therapy. Most of these patients have poor outcome. Hence, the management of pregnancy-related AKI presents a challenge that requires proper evaluation of causative factors to facilitate appropriate treatment.

Potent Anticancer Effects of Epidithiodiketopiperazine NT1721 in Cutaneous T Cell Lymphoma.

Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of debilitating, incurable malignancies. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes, accounting for ~65% of CTCL cases. Patients with advanced disease have a poor prognosis and low median survival rates of four years. CTCLs develop from malignant skin-homing CD4+ T cells that spread to lymph nodes, blood, bone marrow and viscera in advanced stages. Current treatments options for refractory or advanced CTCL, including chemotherapeutic and biological approaches, rarely lead to durable responses. The exact molecular mechanisms of CTCL pathology remain unclear despite numerous genomic and gene expression profile studies. However, apoptosis resistance is thought to play a major role in the accumulation of malignant T cells. Here we show that NT1721, a synthetic epidithiodiketopiperazine based on a natural product, reduced cell viability at nanomolar concentrations in CTCL cell lines, while largely sparing normal CD4+ cells. Treatment of CTCL cells with NT1721 reduced proliferation and potently induced apoptosis. NT1721 mediated the downregulation of GLI1 transcription factor, which was associated with decreased STAT3 activation and the reduced expression of downstream antiapoptotic proteins (BCL2 and BCL-xL). Importantly, NT1721, which is orally available, reduced tumor growth in two CTCL mouse models significantly better than two clinically used drugs (romidepsin, gemcitabine). Moreover, a combination of NT1721 with gemcitabine reduced the tumor growth significantly better than the single drugs. Taken together, these results suggest that NT1721 may be a promising new agent for the treatment of CTCLs.

Correction: Lin et al. Potent Anticancer Effects of Epidithiodiketopiperazine NT1721 in Cutaneous T Cell Lymphoma. Cancers 2021, 13, 3367.

There is an omission in the Institutional Review Board Statement and Conflict of Interest statements of the paper [...].

Adsorption of cationic dyes, drugs and metal from aqueous solutions using a polymer composite of magnetic/ß-cyclodextrin/activated charcoal/Na alginate: Isotherm, kinetics and regeneration studies.

In this work, we successfully synthesized novel polymer gel beads based on functionalized iron oxide (Fe3O4), activated charcoal (AC) particles with ß-cyclodextrin (CD) and sodium alginate (SA) polymer (Fe3O4/CD/AC/SA), by a simple, reproducible and inexpensive method. These beads proved to be versatile and strong adsorbents with magnetic properties and high adsorption capacity. The composites were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, vibrating sample magnetometry, adsorption at -196 °C, high resolution transmission electron microscopy, thermogravimetric analysis and point of zero charge measurements. Two dyes, two drugs and one metal were used to test the adsorption capability of the prepared polymer nanocomposite. The adsorbent showed good removal efficiencies for the studied pollutants, especially the cationic dyes and the metal, when compared to other low-cost adsorbents. The saturated adsorption capacity of Fe3O4/CD/AC/SA reached 5.882 mg g-1 for methyl violet (MV), 2.283 mg g-1 for brilliant green (BG), 2.551 mg g-1 for norfloxacin (NOX), 3.125 mg g-1 for ciprofloxacin (CPX), 10.10 mg g-1 for copper metal ion (Cu(II)). The adsorption isotherm studies showed that data fitted well with Langmuir and Temkin isotherms models. The kinetic data showed good correlation coefficient with low error function for the pseudo-second order kinetic model. The data analysis was carried out using error and regression coefficient functions for the estimation of best-fitting isotherm and kinetic models, namely: chi-square test (χ2) and sum of the squares of errors (SSE). The activation energy was found to be 47.68 kJ mol-1 for BG, 29.09 kJ mol-1 for MV, 28.93 kJ mol-1 for NOX, 4.53 kJ mol-1 for CPX and 17.08 kJ mol-1 for Cu(II), which represent chemisorption and physisorption behavior of sorbent molecules. The polymer composites can be regenerated and easily separated from aqueous solution without any weight loss. After regeneration, the Fe3O4/CD/AC/SA beads still have good adsorption capacities up to four cycles of desorption and adsorption. The results indicate that the polymer gel beads are promising adsorbents for the removal of different categories of toxicants (like dyes, drugs and metal) in single adsorbate aqueous systems. Thus, the novel Fe3O4/CD/AC/SA beads can be effectively employed for a large-scale applications as environmentally compatible materials for the adsorption of different categories of pollutants.

Methionine-Functionalized Graphene Oxide/Sodium Alginate Bio-Polymer Nanocomposite Hydrogel Beads: Synthesis, Isotherm and Kinetic Studies for an Adsorptive Removal of Fluoroquinolone Antibiotics.

In spite of the growing demand for new antibiotics, in the recent years, the occurrence of fluoroquinolone antibiotics (as a curative agent for urinary tract disorders and respiratory problems) in wastewater have drawn immense attention. Traces of antibiotic left-overs are present in the water system, causing noxious impact on human health and ecological environments, being a global concern. Our present work aims at tackling the major challenge of toxicity caused by antibiotics. This study deals with the efficient adsorption of two commonly used fluoroquinolone (FQ) antibiotics, i.e., Ofloxacin (OFX) and Moxifloxacin (MOX) on spherical hydrogel beads generated from methionine‒functionalized graphene oxide/ sodium alginate polymer (abbreviated Met-GO/SA) from aqueous solutions. The composition, morphology and crystal phase of prepared adsorbents were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FTIR), high-resolution transmission electron microscopy (HR-TEM) and thermogravimetric analysis/differential thermogravimetry (TGA/DTG). Batch adsorption tests are followed to optimize the conditions required for adsorption process. Both functionalized and non-functionalized adsorbents were compared to understand the influence of several experimental parameters, such as, the solution pH, contact time, adsorbent dosage, temperature and initial concentration of OFX and MOX on adsorption. The obtained results indicated that the functionalized adsorbent (Met-GO/SA) showed a better adsorption efficiency when compared to non-functionalized (GO/SA) adsorbent. Further, the Langmuir isotherm was validated as the best fitting model to describe adsorption equilibrium and pseudo second-order-kinetic model fitted well for both types of adsorbate. The maximum adsorption capacities of Met-GO/SA were 4.11 mg/g for MOX and 3.43 mg/g for OFX. Thermodynamic parameters, i.e., ∆G°, ∆H° and ∆S° were also calculated. It was shown that the overall adsorption process was thermodynamically favorable, spontaneous and exothermic in nature. The adsorbents were successfully regenerated up to four cycles with 0.005 M NaCl solutions. Overall, our work showed that the novel Met-GO/SA nanocomposite could better contribute to the removal of MOX and OFX from the liquid media. The gel beads prepared have adequate features, such as simple handling, eco-friendliness and easy recovery. Hence, polymer gel beads are promising candidates as adsorbents for large-scale water remediation.

CuO assisted borate 1393B3 glass scaffold with enhanced mechanical performance and cytocompatibility: An In vitro study.

Herein, three dimensional porous 1393B3 borate-based glass (BBG) scaffold along with their CuO derivatives (C1BBG, C2BBG, and C3BBG) tailored with trabecular bones' architecture were prepared by melt-quench route followed by foam replica technique. The properties of 'CuO incorporated' scaffolds, as compared to 'as prepared' scaffold were analyzed by a series of In vitro investigations for enhancement in biological compatibility, bioactivity, and physicomechanical performances. The in vitro study demonstrates superior mechanochemical stability of CBBGs (CuO derived 1393B3) than the pure BBG, while causing no or minimal effect on bioactivity and cytocompatibility post CuO incorporation to the BBG. In fact, the biological compatibility examined through MTT, Live/Dead, and cell adhesion study using the L929 cell lines was enhanced in the CBBGs up to 1% CuO incorporated scaffolds (C1BBG and C2BBG) in most cases. However, the enhanced biological compatibility was observed in C1BBG in comparison to other BBGs. Thus, the CuO incorporation into BBG enhanced mechanochemical and biological performance without affecting the bioactivity of the scaffold; henceforth, CBBGs could be considered neo bone tissue regenerative biomaterials.

Mechanisms of 4-hydroxy-2-nonenal induced pro- and anti-apoptotic signaling.

In recent years, 4-hydroxy-2-nonenal (4-HNE) has emerged as an important second messenger in cell cycle signaling. Here, we demonstrate that 4-HNE induces signaling for apoptosis via both the Fas-mediated extrinsic and the p53-mediated intrinsic pathways in HepG2 cells. 4-HNE induces a Fas-mediated DISC independent apoptosis pathway by activating ASK1, JNK, and caspase-3. Parallel treatment of 4-HNE to HepG2 cells also induces apoptosis by the p53 pathway through activation of Bax, p21, JNK, and caspase-3. Exposure of HepG2 cells to 4-HNE leads to the activation of both Fas and Daxx, promotes the export of Daxx from the nucleus to cytoplasm, and facilitates Fas-Daxx binding. Depletion of Daxx by siRNA results in the potentiation of apoptosis, indicating that Fas-Daxx binding in fact is inhibitory to Fas-mediated apoptosis in cells. 4-HNE-induced translocation of Daxx is also accompanied by the activation and nuclear accumulation of HSF1 and up-regulation of heat shock protein Hsp70. All these effects of 4-HNE in cells can be attenuated by ectopic expression of hGSTA4-4, the isozyme of glutathione S-transferase with high activity for 4-HNE. Through immunoprecipitation and liquid chromatography-tandem mass spectrometry, we have demonstrated the covalent binding of 4-HNE to Daxx. We also demonstrate that 4-HNE modification induces phosphorylation of Daxx at Ser668 and Ser671 to facilitate its cytoplasmic export. These results indicate that while 4-HNE exhibits toxicity through several mechanisms, in parallel it evokes signaling for defense mechanisms to self-regulate its toxicity and can simultaneously affect multiple signaling pathways through its interactions with membrane receptors and transcription factors/repressors.

Rlip76 transports sunitinib and sorafenib and mediates drug resistance in kidney cancer.

RLIP76 is a stress-responsive membrane protein implicated in the regulation of multiple cellular signaling pathways. It represents the predominant glutathione-conjugate (GS-E) transporter in cells. We have shown that RLIP76 plays a crucial role in defending cancer cells from radiation and chemotherapeutic toxin-mediated apoptosis, and that its inhibition by antibodies or depletion by siRNA or antisense causes apoptosis in a number of cancer cell types. We demonstrated for the first time that the striking anti-neoplastic effects with no evident toxicity in terms of either weight loss or metabolic effects are also demonstrable for the antibody, antisense and siRNA in a renal cell xenografts model of Caki-2 cells (Singhal et al., Cancer Res., 2009, 69: 4244). Present studies were performed to determine if RLIP76 targeting is more broadly applicable in other kidney cancer cell lines, to compare the signaling effects of RLIP76 antisense with kinase inhibitors used in treatment of renal cell carcinoma, and to determine whether kinase inhibitors were substrates for transport by RLIP76. Results of these studies show that sorafenib as well as sunitinib are substrates for transport by RLIP76 thus are competitive inhibitors of GS-E transport. Furthermore, kinase inhibition in the ERK as well as PI3K pathways by RLIP76 depletion is more profound and consistent and is more widely apparent in a number of renal carcinoma cell lines. These studies offer strong support for our overall hypothesis that RLIP76 is an overarching anti-apoptosis mechanism that, if inhibited, can be more broadly effective in the treatment of renal cell carcinoma.