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.

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.

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.

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.

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 [...].

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.

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.

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.

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.

Solvation Shell of the Nitrite Ion in Water: An Ab Initio Molecular Dynamics Study.

We performed ab initio molecular dynamics simulation of a nitrite ion in water to investigate the structural and dynamical properties of its hydration shell. The nitrite ion is found to exhibit strong asymmetry toward hydrogen bonding due to its two different types of hydrogen bond acceptor sites. This difference is better captured through further partitioning of the hydration shell into its proximal and distal regions. The frequency shifts of the stretch modes of hydration shell water reveal that the nitrogen site forms a stronger hydrogen bond than its oxygen sites with the latter forming hydrogen bonds, which are similar in strength to that between a pair of water molecules. The escape dynamics of water from the hydration shell is found to be rather slow, which seems to classify the nitrite ion as a structure-maker. However, the dynamics of orientational and hydrogen bond relaxation reveal a faster mobility of water molecules in the hydration shell than bulk water in spite of strong ion-water interactions. It is found that the nitrite ion can hold water molecules in its solvation shell and still make them rotate fast in its vicinity through switching of their hydrogen bonds between its nitrogen and oxygen acceptor sites. The dipole moment of the solute in water is also calculated in the present study.

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.

Rlip Depletion Suppresses Growth of Breast Cancer.

RLIP76 (RAL-binding protein-1, Rlip) is a stress-protective mercapturic-acid-pathway transporter protein that also plays a key role in regulating clathrin-dependent endocytosis as a Ral effector. Targeted inhibition or depletion of Rlip causes regression of xenografts of many cancers and is capable of abrogating tumor formation in p53-null mice. This is associated with the reversion of the abnormal methylomic profile of p53-null mice to wild-type. In a query of The Cancer Genome Atlas (TCGA) databases, we found that Rlip expression was associated with poor survival and with significant differences in the frequencies of PIK3CA mutation, MYC amplification, and CDKN2A/B deletion, which were the most commonly mutated, amplified, and deleted genes, respectively, among TCGA breast cancer patients. We conducted the present study to further examine the effects of Rlip inhibition and to evaluate the in vitro and in vivo efficacy in breast cancer. Using immunogold electron microscopy, we found that plasma-membrane Rlip was accessible to cell-surface antibodies in the MCF7 (ER+) breast cancer cell line. Rlip depletion resulted in decreased survival of MCF7 and MDA-MB-231 cells and increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity and DNA laddering, indicating apoptotic cell death. Additionally, in vitro knockdown of Rlip inhibited EGF endocytosis and WNT/MAPK signaling. Xenograft studies in nude mice showed regression of breast cancer via antisense-mediated depletion of Rlip mRNA as well as by anti-Rlip antibody. Finally, knockdown of Rlip by antisense locked nucleic acid oligonucleotides increased markers for apoptotic signaling and decreased markers for proliferation, angiogenesis, and cell cycling in MCF7 and MDA-MB-231luc xenografts. Our findings validate Rlip as an attractive target in breast cancer.

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.

Cationic Dye Removal Using Novel Magnetic/Activated Charcoal/ß-Cyclodextrin/Alginate Polymer Nanocomposite.

New magnetic iron oxide (Fe3O4)/activated charcoal (AC)/ß-cyclodextrin (CD)/sodium alginate (Alg) polymer nanocomposite materials were prepared by direct mixing of the polymer matrix with the nanofillers. The obtained materials were utilized as nano-adsorbents for the elimination of methylene blue (MB), a hazardous water-soluble cationic dye, from aqueous solutions, and showed excellent regeneration capacity. The formation of the nanocomposites was followed by high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM) equipped with energy dispersive X-ray spectrometry (EDX), Fourier-transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), X-ray diffraction (XRD) and adsorption of N2 at -196 °C. The rate of adsorption was investigated varying several factors, namely contact time, pH, amount of adsorbent and MB concentration on the adsorption process. Studies dealing with equilibrium and kinetics were carried out in batch conditions. The obtained results indicated that the removal rate of MB was 99.53% in 90 min. Langmuir's isotherm fitted better to the equilibrium data of MB. Fe3O4/AC/CD/Alg polymer beads shows amazing adsorption capacities in the elimination of cationic dyes (2.079 mg/g for polymer gel beads and 10.63 mg g-1 for dry powder beads), in comparison to other adsorbent materials. The obtained adsorbent is spherical with hydrophobic cross-linked surface properties that enable an easy recovery without any significant weight loss of in the adsorbent used.

Effect of three different compositions of topical fluoride varnishes with and without prior oral prophylaxis on Streptococcus mutans count in biofilm samples of children aged 2-8 years: A randomized controlled trial.

BACKGROUND: Various strategies for controlling caries focus on disrupting the interaction between risk factors. Of these, fluoride varnish has been shown to reduce the colony-forming (CFU) units and water-insoluble extracellular polysaccharide amount. Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and xylitol-containing fluoride varnishes have recently gained importance as caries-protective fluoride varnishes. AIM: This study aims to assess and compare the reduction in Streptococcus mutans count in biofilm samples after topical application of three different fluoride varnishes and to evaluate the effect of oral prophylaxis prior to fluoride varnish application. MATERIALS AND METHODS: Sixty healthy children with no active caries, in the age group of 2-8 years, were randomly divided into Group A = fluoride varnish containing CPP-ACP; Group B = fluoride varnish containing xylitol; and Group C = fluoride varnish with 0.9% difluorosilane; further, the groups were divided into two subgroups, namely A1, B1, and C1 with prior oral prophylaxis and A2, B2, and C2 without oral prophylaxis. Plaque samples were collected at baseline, 1st month, and 3rd month; cultured; and incubated, and CFU/ml was calculated. RESULTS: Data were compiled, and CFU/ml was analyzed by independent t-test, paired t-test, and one-way ANOVA. There was no statistical difference between the fluoride groups. Furthermore, no statistically significant difference was seen between the subgroups. CONCLUSION: Fluoride varnish containing CPP-ACP showed higher reduction in S. mutans count followed by xylitol-containing fluoride varnish and Fluor Protector®. There was no effect of prior oral prophylaxis on the efficacy of fluoride varnish.

To Study the Impact of Donor Nephrectomy on Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring and Renal Function.

Prospective living kidney donors need meticulous evaluation prior to kidney donation. Ambulatory blood pressure monitoring (ABPM) is considered the reference standard for diagnosing hypertension. With no prior study available in India in this context, we undertook this study to evaluate the utility of ABPM in kidney donors and effect of donor nephrectomy on renal function. This was a prospective observational study involving healthy prospective kidney donors between 18 and 70 years with normal office blood pressure measurements (OBPM). Detailed clinical and biochemical parameters were recorded. OBPM and 24-hour ABPM was done preoperatively and 3 months following donor nephrectomy. There were 51 donors with a mean age of 46.1 ± 11.3 years, of which 40 (78.4%) were females. Preoperatively, three (5.8%) donors were hypertensive on ABPM but normal on OBPM (P = 0.08). Three months post nephrectomy, hypertension was present in seven (13.7%) donors by ABPM, while only two (3.9%) donors were diagnosed as hypertensive by OBPM (P = 0.02). Median pre-nephrectomy proteinuria was 70 mg (10 mg-180 mg) with a mean estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula of 86.86 ± 19.1 ml/min. Six donors developed >300 mg/day proteinuria, and 17 (33.3%) had a 24-hour urinary protein excretion greater than 150 mg/day. Mean serum creatinine (0.79 ± 0.11 vs 1.03 ± 0.16 mg/dl) significantly increased post donation, more so in donors >55 years of age (1.14 ± 0.25 mg/dl). Our study shows that in transplant donors, ABPM is better for diagnosing hypertension, which otherwise remains masked in 10% of the donors on routine OBPM. Significance of post-nephrectomy hypertension and increasing proteinuria needs further evaluation.

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.

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.

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.

Structural and Dynamical Nature of Hydration Shells of the Carbonate Ion in Water: An Ab Initio Molecular Dynamics Study.

The structural and dynamical nature of hydration shells of the carbonate ion in water is investigated through ab initio molecular dynamics simulation. The anisotropic solvation shell structure of the ion is resolved by calculating conically restricted pair distribution and radial/angular correlation functions. The vibrational frequency of OD modes hydrogen-bonded to the ion is found to be smaller than that of bulk water, which means the carbonate ion-water hydrogen bonds are stronger than those between water molecules. Calculations of the orientational and residence dynamics and translational diffusion reveal retarded mobility of the hydration shell water molecules compared to that of the bulk water due to stronger ion-water interactions. It is shown that the rotation of hydration shell water takes place through dual routes of hydrogen bond switching, where an OD bond initially hydrogen-bonded to a carbonate oxygen switches its hydrogen bond to another carbonate oxygen or to a water oxygen. The carbonate ion is found to have a nonzero dipole moment of 1.0 D in water, which can be attributed to its interactions with the fluctuating environment of the surrounding water. The carbonate ion is also found to have a long-range effect on neighboring water molecules that goes beyond the first solvation shell.