Wilms' tumor 1 (WT1) antigen is overexpressed in Kaposi Sarcoma and is regulated by KSHV vFLIP.

In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed. The Wilms' tumor 1 (WT1) protein is overexpressed and associated with poor prognosis in several hematologic and solid malignancies and has shown promise as an immunotherapeutic target. We found that WT1 was overexpressed in >90% of a total 333 KS biopsies, as determined by immunohistochemistry and image analysis. Our largest cohort from ACTG, consisting of 294 cases was further analyzed demonstrating higher WT1 expression was associated with more advanced histopathologic subtypes. There was a positive correlation between the proportion of infected cells within KS tissues, assessed by expression of the KSHV-encoded latency-associated nuclear antigen (LANA), and WT1 positivity. Areas with high WT1 expression showed sparse T-cell infiltrates, consistent with an immune evasive tumor microenvironment. We show that major oncogenic isoforms of WT1 are overexpressed in primary KS tissue and observed WT1 upregulation upon de novo infection of endothelial cells with KSHV. KSHV latent viral FLICE-inhibitory protein (vFLIP) upregulated total and major isoforms of WT1, but upregulation was not seen after expression of mutant vFLIP that is unable to bind IKKÆ´ and induce NFκB. siRNA targeting of WT1 in latent KSHV infection resulted in decreased total cell number and pAKT, BCL2 and LANA protein expression. Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, demonstrates increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and immunotherapy directed against WT1 may be an approach for KS treatment.

Potent-By-Design: Amino Acids Mimicking Porous Nanotherapeutics with Intrinsic Anticancer Targeting Properties.

Exogenous sources of amino acids are essential nutrients to fuel cancer growth. Here, the increased demand for amino acid displayed by cancer cells is unconventionally exploited as a design principle to replete cancer cells with apoptosis inducing nanoscopic porous amino acid mimics (Nano-PAAM). A small library consisting of nine essential amino acids nanoconjugates (30 nm) are synthesized, and the in vitro anticancer activity is evaluated. Among the Nano-PAAMs, l-phenylalanine functionalized Nano-PAAM (Nano-pPAAM) has emerged as a novel nanotherapeutics with excellent intrinsic anticancer and cancer-selective properties. The therapeutic efficacy of Nano-pPAAM against a panel of human breast, gastric, and skin cancer cells could be ascribed to the specific targeting of the overexpressed human large neutral amino acid transporter SLC7A5 (LAT-1) in cancer cells, and its intracellular reactive oxygen species (ROS) inducing properties of the nanoporous core. At the mechanistic level, it is revealed that Nano-pPAAM could activate both the extrinsic and intrinsic apoptosis pathways to exert a potent "double-whammy" anticancer effect. The potential clinical utility of Nano-pPAAM is further investigated using an MDA-MB-231 xenograft in NOD scid gamma mice, where an overall suppression of tumor growth by 60% is achieved without the aid of any drugs or application of external stimuli.

Hollow Microparticles as a Superior Delivery System over Solid Microparticles for the Encapsulation of Peptides.

PURPOSE: Peptides are gaining significant interests as therapeutic agents due to their high targeting specificity and potency. However, their low bioavailability and short half-lives limit their massive potential as therapeutics. The use of dense, solid particles of biodegradable polymer as a universal carrier for peptides also has its challenges, such as inefficient peptide release and low bioactivity. In this paper, it was established that hollow microparticles (h-MPs) instead of solid microparticles (s-MPs), as peptide carriers, could improve the release efficiency, while better preserving their bioactivity. METHODS: Glucagon like Peptide-1 (GLP-1) was encapsulated as a model peptide. Mass loss, average molecular weight changes, intraparticle pH, polymer-peptide interaction and release studies, together with bioactivity assessment of the peptide for s-MPs and h-MPs were systematically analyzed and evaluated for efficacy. RESULTS: The intraparticle pH of s-MPs was as low as 2.64 whereas the pH of h-MPs was 4.99 by day 7. Consequently, 93% of the peptide extracted from h-MPs was still bioactive while only 58% of the peptide extracted from s-MPs was bioactive. Likewise, the cumulative release of GLP-1 by day 14 from h-MPs showed a cumulative amount of 88 ± 8% as compared to 33 ± 6% for s-MPs. CONCLUSIONS: The cumulative release of peptide can be significantly improved, and the bioactivity can be better preserved by simply using h-MPs instead of s-MPs as carriers.

Paradoxical septic embolism in an Ebstein's anomaly patient leading to brain abscess: A case report.

Ebstein's anomaly (EA), a congenital cardiac anomaly, is characterized by apical displacement of the tricuspid valve leaflet(s) into the right ventricle. We present the case of a 61-year-old female with a history of EA, Wolff-Parkinson-White syndrome, and patent foramen ovale (PFO), who presented with worsening hypoxia and confusion, in the setting of left lower extremity cellulitis and abscess. The computed tomography (CT) scan of the head showed a cerebellar infarct with hemorrhagic conversion. Magnetic resonance imaging of the head showed a satellite lesion raising concern for the embolic nature of infarcts. After ruling out cardioembolic causes of cerebellar infarction, her presenting symptoms were attributed to paradoxical septic emboli from the left leg abscess (demonstrated on CT scan of the leg). She was deemed a poor candidate for surgical closure of PFO due to contraindication to use heparin (due to the presence of hemorrhagic stroke) and underlying comorbidities. Septic embolization is a rare but dreaded complication in EA patients with PFO. Learning objective: •Paradoxical emboli can occur in patients with Ebstein's anomaly (EA) and patent foramen ovale (PFO).•The mainstay of management in case of paradoxical embolism lies with the identification and treatment of the underlying cause, such as infective endocarditis, deep vein thrombosis, or infectious source, as in the present case.•The surgical correction of PFO in EA patients should be considered when the patient becomes symptomatic with cyanosis, hypoxia, or manifestations of paradoxical emboli.

Comparison of Cardiac Indices Using Two Different Concentrations of Topical Adrenaline during Endoscopic Transsphenoidal Pituitary Surgery: A Prospective Randomized Observational Study.

Introduction Adrenaline-soaked wicks are often employed to decongest nasal mucosa during transsphenoidal pituitary surgeries to ensure proper hemostasis and visibility of the operating field. Considerable debate exists regarding the optimum concentration of adrenaline that strikes a balance between hemostasis as well as the hemodynamic side effects of adrenaline. This study assessed cardiac indices like cardiac output and cardiac index using a FloTrac Vigileo cardiac output monitor to compare two different concentrations of adrenaline used for topical instillation. Materials and Methods 60 adult patients undergoing transsphenoidal pituitary surgery were randomly assigned to receive cotton wicks soaked in adrenaline solution (either 1:100,000 or 1:200,000) for nasal decongestion. Following a standardized anesthetic regime, a FloTrac Vigileo cardiac output monitor was attached with the invasive arterial line for precise monitoring and recording of cardiac indices (cardiac output and cardiac index). Additionally, quality of surgical field (as reported by the operating surgeon) blood loss, incidences of adverse hemodynamic events, and rescue drug usage were recorded. Results No difference in cardiac outputs and cardiac indexes of the patients was observed during baseline to 55 minutes and at 80 minutes and onward, whereas difference rose to statistical significance at the time points of 60 minutes and 70 minutes ( p < 0.05). Other parameters like stroke volume, stroke volume variation, and hemodynamic parameters were similar. Quality of the surgical fields (as reported by the surgeon), intraoperative bleeding, incidences of adverse effects, and frequency of rescue drugs usage were similar. Conclusion Instillation of 1:100,000 dilution of adrenaline solution compared with 1:200,000 for nasal decongestion is associated with significant rise in cardiac output and cardiac index at 60 and 70 minutes of the surgery with similar blood loss and hemodynamic variables. Therefore, the lower concentration of adrenaline can be recommended for usage during transsphenoidal pituitary surgeries.

COVID-19 and chronic kidney disease: an updated overview of reviews.

BACKGROUND: Coronavirus disease (COVID-19) has resulted in the death of more than 3.5 million people worldwide. While COVID-19 mostly affects the lungs, different comorbidities can have an impact on its outcomes. We performed an overview of reviews to assess the effect of Chronic Kidney Disease (CKD) on contracting COVID-19, hospitalization, mortality, and disease severity. METHODS: We searched published and preprint databases. We updated the reviews by searching for primary studies published after August 2020, and prioritized reviews that are most updated and of higher quality using the AMSTAR tool. RESULTS: We included 69 systematic reviews and 66 primary studies. Twenty-eight reviews reported on the prevalence of CKD among patients with COVID-19, which ranged from 0.4 to 49.0%. One systematic review showed an increased risk of hospitalization in patients with CKD and COVID-19 (RR = 1.63, 95% CI 1.03-2.58) (Moderate certainty). Primary studies also showed a statistically significant increase of hospitalization in such patients. Thirty-seven systematic reviews assessed mortality risk in patients with CKD and COVID-19. The pooled estimates from primary studies for mortality in patients with CKD and COVID-19 showed a HR of 1.48 (95% CI 1.33-1.65) (Moderate certainty), an OR of 1.77 (95% CI 1.54-2.02) (Moderate certainty) and a RR of 1.6 (95% CI 0.88-2.92) (Low certainty). CONCLUSIONS: Our review highlights the impact of CKD on the poor outcomes of COVID-19, underscoring the importance of identifying strategies to prevent COVID-19 infection among patients with CKD.

Comparison of Conventional Oxygen Therapy With High-Flow Nasal Oxygenation in the Management of Hypercapnic Respiratory Failure.

INTRODUCTION: The effectiveness of high-flow nasal oxygenation (HFNO) in patients with hypercapnic respiratory failure (RF) remains controversial. The current study compared the effectiveness of HFNO in patients with hypercapnic RF with conventional oxygen therapy (COT). OBJECTIVES: The primary objective was to compare changes in the partial pressure of carbon dioxide (PaCO2) between those receiving COT and HFNO. The secondary objectives were to compare changes in the partial pressure of oxygen (PaO2), oxygen saturation (SpO2), respiratory rate (RR), serum bicarbonate level, base excess, lactate level, and incidence of the need for non-invasive ventilation (NIV) and mechanical ventilation (MV). METHODS: We recruited 30 patients with mild to moderate hypercapnic RF in the HFNO group, and data of 30 patients from historical controls, who matched the inclusion criteria, were obtained from medical records for comparison (COT group). The study was terminated after two hours, and patients were managed per the existing protocol after that. Arterial blood gas (ABG) analysis was repeated at the baseline, first, second, and third hours. RESULTS: In the COT group, the mean RR at the baseline, first, second, and third hours was 24.5 ± 2.61, 24.9 ± 3.03, 26.03 ± 3.4, and 22.90 ± 1.86, whereas, in the HFNO group, it was 25.93 ± 3.91, 23.00 ± 3.54, 22.50 ± 3.38, and 21.90 ± 3.57, respectively. The mean PaCO2 in the COT vs. HFNO groups was 54.45 ± 5.83 vs. 62.22 ± 9.15, 57.74 ± 6.05 vs. 58.65 ± 10.43, 60.79 ± 7.48 vs. 60.41 ± 11.24, and 55.23 ± 6.63 vs. 56.95 ± 10.31. The mean SpO2 in the COT group at these points of time was 94.50 ± 1.46, 95.4 ± 1.28, 96.10 ± 1.84, and 97.53 ± 2.05, whereas, in the HFNO group, it was 95.40 ± 2.55, 98.63 ± 1.43, 99.00 ± 1.66, and 99.50 ± 1.31, respectively. The patients who needed NIV after the study period were 50% and 36.67% in the COT and HFNO groups, respectively. CONCLUSIONS: There was no change in PaCO2 levels with HFNO, but there was a significant improvement in SpO2 and PaO2 levels and a decreased RR. Following the termination of the study protocol, more patients in the COT group needed NIV than those in the HFNO group.

Valorizing okara waste into nutritionally rich polysaccharide/protein-extracts for co-encapsulation of ß-carotene and ferrous sulphate as a potential approach to tackle micronutrient malnutrition.

Colossal amounts of food waste are generated and discarded daily at the expense of financial resources and at a detriment to the environment. One such food waste, okara - a soybean by-product, is valorized in this study by upcycling it into nutritional extracts for micronutrients encapsulation. Micronutrient malnutrition, particularly in the developing world, is a major public health challenge. Herein, okara extracts were obtained through a low-cost extraction process and was subsequently developed as an encapsulant material for micronutrients ß-carotene, and ferrous sulphate encapsulation, using zein as an excipient. Spray-drying, as a scalable technique, was employed to produce various formulations which were assessed for release profiles, shelf-life, ß-carotene antioxidant activity and cell cytotoxicity. Finally, an optimized dual-micronutrient formulation displayed a sequential release with ferrous sulphate releasing in simulated gastric fluid, and ß-carotene releasing predominantly in simulated intestinal fluid. This sequential release profile favors the absorption of both the micronutrients and could potentially enhance their bioavailability.

Impact of congestive heart failure and role of cardiac biomarkers in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been reported to cause worse outcomes in patients with underlying cardiovascular disease, especially in patients with acute cardiac injury, which is determined by elevated levels of high-sensitivity troponin. There is a paucity of data on the impact of congestive heart failure (CHF) on outcomes in COVID-19 patients. METHODS: We conducted a literature search of PubMed/Medline, EMBASE, and Google Scholar databases from 11/1/2019 till 06/07/2020, and identified all relevant studies reporting cardiovascular comorbidities, cardiac biomarkers, disease severity, and survival. Pooled data from the selected studies was used for metanalysis to identify the impact of risk factors and cardiac biomarker elevation on disease severity and/or mortality. RESULTS: We collected pooled data on 5967 COVID-19 patients from 20 individual studies. We found that both non-survivors and those with severe disease had an increased risk of acute cardiac injury and cardiac arrhythmias, our pooled relative risk (RR) was - 8.52 (95% CI 3.63-19.98) (p < 0.001); and 3.61 (95% CI 2.03-6.43) (p = 0.001), respectively. Mean difference in the levels of Troponin-I, CK-MB, and NT-proBNP was higher in deceased and severely infected patients. The RR of in-hospital mortality was 2.35 (95% CI 1.18-4.70) (p = 0.022) and 1.52 (95% CI 1.12-2.05) (p = 0.008) among patients who had pre-existing CHF and hypertension, respectively. CONCLUSION: Cardiac involvement in COVID-19 infection appears to significantly adversely impact patient prognosis and survival. Pre-existence of CHF, and high cardiac biomarkers like NT-pro BNP and CK-MB levels in COVID-19 patients correlates with worse outcomes.

Evidence that Gag facilitates HIV-1 envelope association both in GPI-enriched plasma membrane and detergent resistant membranes and facilitates envelope incorporation onto virions in primary CD4+ T cells.

HIV-1 particle assembly mediated by viral Gag protein occurs predominantly at plasma membrane. While colocalization of HIV-1 envelope with lipid rich microenvironment have been shown in T cells, the significance of viral proteins modulating envelope association in such microdomains in plasma membrane enriched in glycosylphosphatidylinositol-anchored proteins in primary CD4+ T cells that are natural targets of HIV-1 is poorly understood. Here we show that in primary CD4+ T cells that are natural targets of HIV-1 in vivo, Gag modulates HIV-1 envelope association with GM1 ganglioside and CD59 rich cellular compartments as well as with detergent resistant membranes. Our data strengthen evidence that Gag-Env interaction is important in envelope association with lipid rafts containing GPI-anchored proteins for efficient assembly onto mature virions resulting in productive infection of primary CD4+ T cells.

Dosimetric characteristics of a single use MOSFET dosimeter for in vivo dosimetry in proton therapy.

PURPOSE: Entrance dose (or skin dose) is an important part of patient quality assurance in external beam radiation therapy. However, entrance dose verification in proton beam is not routinely performed. In this study, the OneDose single use MOSFET detector system for in vivo dosimetry measurement in proton therapy is investigated. METHODS: Using a solid water phantom, several fundamental dosimetric characteristics of the OneDose system are studied with a proton beam: The reproducibility (consistency) of the dosimeter, the linearity with dose and dose rate, energy dependence, directional dependence, LET dependence, and fading (delay readout with time) is studied. RESULTS: OneDose detectors show dose and dose rate linearity but exhibit pronounced energy dependence at depth and a large variation in dose response with LET. On the other hand, the detector response remain relatively constant (within 3%) at surface over a wide range of energies. There is also a slight angular dependence (about 2%) up to 60 degrees angle of incidence. However, detector orientation such that incidence along the long axis of the detector should be avoided as the proton beam will have to traverse a large amount of the copper backing. Since most in vivo dosimetry involves entrance dose measurement, the OneDose at surface appears to be well suited for such application. OneDose exhibits small intrabatch variation (< or = 2% at one SD) indicating that it is only necessary to calibration a few detectors from each batch. The interbatch variation is generally within 3%. CONCLUSIONS: The small detector size and its relatively flexible design of OneDose allow dose measurement to be performed on a curved surface or in small cavities that is otherwise difficult with the conventional diode detectors. The slight drawback in its angular dependence can be easily handled by angular dependence table. However, since OneDose is a single use detector, the intra-batch consistency must be verified before the remaining detectors from the same batch could be used for in vivo dosimetry. It is advisable that the detectors from the same batch be taken for the same application to reduce the dosimetric uncertainty. For detectors from different batches, inter-batch consistency should also be verified to obtain reliable results. OneDose provides an opportunity to measure in vivo dose with proton beam within acceptable clinical criterion of +/- (5.0%-6.5%).

Hydroxyapatite Particles Induced Modulation of Collagen Expression and Secretion in Primary Human Dermal Fibroblasts.

BACKGROUND: Hydroxyapatite (HA) [Ca5(PO4)3(OH)] is a naturally occurring calcium phosphate which makes up 60-70% of the dry weight of human bones. Nano-scale HA particles are increasingly being used as carriers for controlled and targeted delivery of bioactive agents like drugs, proteins, and nucleic acids due to their high porosity, negative charge, and biodegradability. PURPOSE: Although much effort has been devoted to understanding the delivery kinetics and effects of the payloads in such carriers, a thorough understanding of the influence of the carriers themselves is lacking. METHODS: HA particles (300 µg/mL) were administered to primary human dermal fibroblasts (HDFs). The uptake and intracellular localization of the particles were determined by flow cytometry, confocal imaging, and transmission electron microscopy (TEM). Immunological assays and PCR were performed to determine the levels of pro-inflammatory cytokines and collagens in cell lysates and media supernatant. RESULTS: The current study explores the effects of poly-dispersed HA particles on primary HDFs as a model system. The majority of the particles were determined to range between 150 and 200 nm in diameter. Upon exposure to HA suspensions, primary HDFs internalized the particles by endocytosis within 6 hours of exposure, showing maximum uptake at 72 hours following which the particles were exocytosed by 168 hours. This correlated to reduced secretion of various pro-inflammatory and pro-collagenic cytokines. Biochemical analysis further revealed a reduction in Type I collagen expression and secretion. CONCLUSION: HA particles have an immune-modulatory effect on dermal fibroblasts and reduce collagen production, which may impact the integrity of the extracellular matrix (ECM). This study demonstrates the need to consider the secondary effects of particulate carriers like HA, beyond basic cytotoxicity, in the specific tissue environment where the intended function is to be realized.

Modulation of virus-induced NF-κB signaling by NEMO coiled coil mimics.

Protein-protein interactions featuring intricate binding epitopes remain challenging targets for synthetic inhibitors. Interactions of NEMO, a scaffolding protein central to NF-κB signaling, exemplify this challenge. Various regulators are known to interact with different coiled coil regions of NEMO, but the topological complexity of this protein has limited inhibitor design. We undertook a comprehensive effort to block the interaction between vFLIP, a Kaposi's sarcoma herpesviral oncoprotein, and NEMO using small molecule screening and rational design. Our efforts reveal that a tertiary protein structure mimic of NEMO is necessary for potent inhibition. The rationally designed mimic engages vFLIP directly causing complex disruption, protein degradation and suppression of NF-κB signaling in primary effusion lymphoma (PEL). NEMO mimic treatment induces cell death and delays tumor growth in a PEL xenograft model. Our studies with this inhibitor reveal the critical nexus of signaling complex stability in the regulation of NF-κB by a viral oncoprotein.

The protein corona determines the cytotoxicity of nanodiamonds: implications of corona formation and its remodelling on nanodiamond applications in biomedical imaging and drug delivery.

The use of nanodiamonds for biomedical and consumer applications is growing rapidly. As their use becomes more widespread, so too do concerns around their cytotoxicity. The cytotoxicity of nanodiamonds correlates with their cellular internalisation and circulation time in the body. Both internalisation and circulation time are influenced by the formation of a protein corona on the nanodiamond surface. However, a precise understanding of both how the corona forms and evolves and its influence on cytotoxicity is lacking. Here, we investigated protein corona formation and evolution in response to two classes of nanodiamonds, pristine and aminated, and two types of proteins, bovine serum albumin and fibronectin. Specifically, we found that a corona made of bovine serum albumin (BSA), which represents the most abundant protein in blood plasma, reduced nanodiamond agglomeration. Fibronectin (FN9-10), the second most abundant protein found in the plasma, exhibited a significantly higher nanodiamond binding affinity than BSA, irrespective of the nanodiamond surface charge. Finally, nanodiamonds with a BSA corona displayed less cytotoxicity towards nonphagocytic liver cells. However, regardless of the type of corona (FN9-10 or BSA), both classes of nanodiamonds induced substantial phagocytic cell death. Our results emphasise that a precise understanding of the corona composition is fundamental to determining the fate of nanoparticles in the body.

A Rare Case of Sudden Death in a Patient with Takotsubo Cardiomyopathy Secondary to Cardiac Rupture.

Takotsubo cardiomyopathy (TCM), also known as broken heart syndrome or stress-induced cardiomyopathy, is a rare condition with an estimated incidence of 0.02% of all hospitalizations in United States and 2% of all acute coronary syndrome presentations. TCM predominately presents as a transient wall motion abnormality of the left ventricular apex due to emotional or physical stress. Cardiac rupture in the setting of TCM is an extremely rare phenomenon with limited published case reports. We present a case of a 75-year-old female who had cardiac rupture secondary to TCM and performed a literature review using Ovid MEDLINE for published cases showing this association. After the literature review, we found 20 cases showing this association, which are listed in a tabular fashion.

Pomegranate activates TFEB to promote autophagy-lysosomal fitness and mitophagy.

Mitochondrial dysfunction underscores aging and diseases. Mitophagy (mitochondria + autophagy) is a quality control pathway that preserves mitochondrial health by targeting damaged mitochondria for autophagic degradation. Hence, molecules or compounds that can augment mitophagy are therapeutic candidates to mitigate mitochondrial-related diseases. However, mitochondrial stress remains the most effective inducer of mitophagy. Thus, identification of mitophagy-inducing regimes that are clinically relevant is favorable. In this study, pomegranate extract (PE) supplementation is shown to stimulate mitophagy. PE activates transcription factor EB (TFEB) to upregulate the expression of autophagy and lysosomal genes for mitochondrial quality control under basal and stress conditions. Basally, PE alters mitochondrial morphology and promotes recruitment of autophagosomes to the mitochondria (mitophagosome formation). Upon onset of mitochondrial stress, PE further augments mitophagosome formation, and engages PINK1 and Parkin to the mitochondria to potentiate mitophagy. This cellular phenomenon of PE-induced mitophagy helps to negate superfluous mitochondrial reactive oxygen species (ROS) production and mitochondrial impairment. Overall, our study highlights the potential of PE supplementation as a physiological therapy to modulate TFEB activity to alleviate mitochondrial dysfunction in aging and mitochondrial-related diseases.

Biological impact of nanodiamond particles - label free, high-resolution methods for nanotoxicity assessment.

Current methods for the assessment of nanoparticle safety that are based on 2D cell culture models and fluorescence-based assays show limited sensitivity and they lack biomimicry. Consequently, the health risks associated with the use of many nanoparticles have not yet been established. There is a need to develop in vitro models that mimic physiology more accurately and enable high throughput assessment. There is also a need to set up new assays that offer high sensitivity and are label-free. Here we developed 'mini-liver' models using scaffold-free bioprinting and used these models together with label-free nanoscale techniques for the assessment of toxicity of nanodiamond produced by laser-assisted technology. Results showed that NDs induced cytotoxicity in a concentration and exposure-time dependent manner. The loss of cell function was confirmed by increased cell stiffness, decreased cell membrane barrier integrity and reduced cells mobility. We further showed that NDs elevated the production of reactive oxygen species and reduced cell viability. Our approach that combined mini-liver models with label-free high-resolution techniques showed improved sensitivity in toxicity assessment. Notably, this approach allowed for label-free semi-high throughput measurements of nanoparticle-cell interactions, thus could be considered as a complementary approach to currently used methods.

EPR, IR and electronic spectral studies on Ni(II) and Cu(II) complexes with N-donor tetradentate [N4] macrocyclic ligand.

Nickel(II) and copper(II) complexes are synthesized with a novel tetradentate macrocyclic ligand, i.e. 2,6,12,16,21,22-hexaaza;3,5,13,15-tetraphenyltricyclo[15,3,1,1(7-11)] docosa;1(21),2,5,7,9,11(22),12,15,17,19-decaene (L) and characterized by the elemental analysis, magnetic susceptibility measurements, mass, 1H NMR, IR, electronic and EPR spectral studies. All the complexes are non-electrolytic in nature. Thus, these may be formulated as [M(L)X2] [M=Ni(II), Cu(II) and X=Cl(-), NO3(-) and (1/2)SO4(2-)]. Ni(II) and Cu(II) complexes show magnetic moments corresponding to two and one unpaired electron, respectively. On the basis of IR, electronic and EPR spectral studies an octahedral geometry has been assigned for Ni(II) and tetragonal geometry for Cu(II) complexes.

Rice straw fermentation by Schizophyllum commune ARC-11 to produce high level of xylanase for its application in pre-bleaching.

Rice straw is valuable resource that has been used as substrate for cost effective production of xylanase under solid-state fermentation by a newly isolated white rot fungi, S. commune ARC-11. Out of eleven carbon sources tested, rice straw was found most effective for the induction of xylanase that produced 4288.3 IU/gds of xylanase by S. commune ARC-11. Maximum xylanase production (6721.9 IU/gds) was observed on 8th day of incubation at temperature (30 °C), initial pH (7.0) and initial moisture content (70.0%). The supplementation of ammonium sulphate (0.08% N, as available nitrogen) enhanced the xylanase production up to 8591.4 IU/gds. The xylanase production by S. commune ARC-11 was further improved by the addition of 0.10%, (w/v) of Tween-20 as surfactant. The maximum xylanase activities were found at pH 5.0 and temperature 55 °C with a longer stability (180 min) at temperature 45, 50 and 55 °C. This xylanase preparation was also evaluated for the pre-bleaching of ethanol-soda pulp from Eulaliopsis binata. An enzyme dosage of 10 IU/g of xylanase resulted maximum decrease in kappa number (14.51%) with a maximum improvement 2.9% in ISO brightness compared to control.