Search Results (10)

Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium. Thirteen patients, median age 13.7 years, were enrolled. Patients had refractory disease with multiple reinduction attempts. Twelve evaluable patients were treated at the recommended phase II dose (established at dose level 1, 3 mg/kg/dose). Four patients (33%) maintained stable disease. This combination was well tolerated, with no dose-limiting toxicities observed. Grade 3–4 adverse events (AEs) were primarily hematological. Febrile neutropenia was the most common AE ≥ grade 3. A trend to improved quality of life was noted. Increases in CD8+ T cells and reductions in CD4+/CD8+ T cells and demethylation were observed. The combination was well tolerated and had an acceptable safety profile in pediatric patients with relapsed/refractory AML. Future studies might explore this combination for the maintenance of remission in children with AML at high risk of relapse. Full article

The anti-oxidant and anti-inflammatory effect of beta-glucogallin (BGG), a plant-derived natural product, was evaluated in both in vitro and in vivo studies. For the in vitro study, the ability of BGG pre-treatment to quench LPS-induced effects compared to LPS alone in macrophages was investigated. It was found that BGG pre-treatment showed a significant decrease in ROS, NO, superoxide, and pro-inflammatory cytokines (TNF-alpha, IL-4, IL-17, IL-1β, and IL-6) and increased reduced glutathione coupled with the restoration of mitochondrial membrane potential. Gene profiling and further validation by qPCR showed that BGG pre-treatment downregulated the LPS-induced expression of c-Fos, Fas, MMP-9, iNOS, COX-2, MyD88, TRIF, TRAF6, TRAM, c-JUN, and NF-κB. We observed that BGG pre-treatment reduced nuclear translocation of LPS-activated NF-κB and thus reduced the subsequent expressions of NLRP3 and IL-1β, indicating the ability of BGG to inhibit inflammasome formation. Molecular docking studies showed that BGG could bind at the active site of TLR4. Finally, in the LPS-driven sepsis mouse model, we showed that pre-treatment with BGG sustained toxic shock, as evident from their 100% survival. Our study clearly showed the therapeutic potential of BGG in toxic shock syndrome. Full article

Cervical cancer (CC) is a preventable disease using proven interventions, specifically prophylactic vaccination, pervasive disease screening, and treatment, but it is still the most frequently diagnosed cancer in women worldwide. Patients with advanced or metastatic CC have a very dismal prognosis and current therapeutic options are very limited. Therefore, understanding the mechanism of metastasis and discovering new therapeutic targets are crucial. New sequencing tools have given a full visualization of the human transcriptome’s composition. Non-coding RNAs (NcRNAs) perform various functions in transcriptional, translational, and post-translational processes through their interactions with proteins, RNA, and even DNA. It has been suggested that ncRNAs act as key regulators of a variety of biological processes, with their expression being tightly controlled under physiological settings. In recent years, and notably in the past decade, significant effort has been made to examine the role of ncRNAs in a variety of human diseases, including cancer. Therefore, shedding light on the functions of ncRNA will aid in our better understanding of CC. In this review, we summarize the emerging roles of ncRNAs in progression, metastasis, therapeutics, chemo-resistance, human papillomavirus (HPV) regulation, metabolic reprogramming, diagnosis, and as a prognostic biomarker of CC. We also discussed the role of ncRNA in the tumor microenvironment and tumor immunology, including cancer stem cells (CSCs) in CC. We also address contemporary technologies such as antisense oligonucleotides, CRISPR–Cas9, and exosomes, as well as their potential applications in targeting ncRNAs to manage CC. Full article

Photodegradation (photolysis) causes the breakdown of organic pesticides molecules by direct or indirect solar radiation energy. Flucetosulfuron herbicide often encounters water bodies. For this reason, it is important to know the behavior of the compound under these stressed conditions. In this context, photodegradation of flucetosulfuron, a sulfonylurea-based herbicide, has been assessed in aqueous media in the presence of photocatalyst TiO₂ and photosensitizers (i.e., H₂O_2, humic acid, and KNO₃) under the influence of ultraviolet (UV) irradiation. The influence of different water systems was also assessed during the photodegradation study. The photodegradation followed the first-order reaction kinetics in each case. The metabolites after photolysis were isolated in pure form by column chromatographic method and characterized using the different spectral data (i.e., XRD, IR, NMR, UV-VIS, and mass spectrometry). The structures of these metabolites were identified based on the spectral data and the plausible photodegradation pathways of flucetosulfuron were suggested. Based on the findings, photocatalyst TiO₂ with the presence of ultraviolet irradiation was found effective for the photodegradation of toxic flucetosulfuron residues under aqueous conditions. Full article

This study evaluated a potential transition of India’s power sector to 100% wind and solar energy sources. Applying a macro-energy IDEEA (Indian Zero Carbon Energy Pathways) model to 32 regions and 114 locations of potential installation of wind energy and 60 locations of solar energy, we evaluated a 100% renewable power system in India as a concept. We considered 153 scenarios with varying sets of generating and balancing technologies to evaluate each intermittent energy source separately and their complementarity. Our analysis confirms the potential technical feasibility and long-term reliability of a 100% renewable system for India, even with solar and wind energy only. Such a dual energy source system can potentially deliver fivefold the annual demand of 2019. The robust, reliable supply can be achieved in the long term, as verified by 41 years of weather data. The required expansion of energy storage and the grid will depend on the wind and solar energy structure and the types of generating technologies. Solar energy mostly requires intraday balancing that can be achieved through storage or demand-side flexibility. Wind energy is more seasonal and spatially scattered, and benefits from the long-distance grid expansion for balancing. The complementarity of the two resources on a spatial scale reduces requirements for energy storage. The demand-side flexibility is the key in developing low-cost supply with minimum curtailments. This can be potentially achieved with the proposed two-level electricity market where electricity prices reflect variability of the supply. A modelled experiment with price signals demonstrates how balancing capacity depends on the price levels of guaranteed and flexible types of loads, and therefore, can be defined by the market. Full article

Organic wastes of rural slaughterhouses in developing countries comprise of blood and undigested rumen contents harboring infectious microbial pathogens and having impermissible BOD₅ and COD values. Previously we demonstrated valorization of blood and rumen contents through drying and conversion to an efficacious organic fertilizer which was free from infectious pathogens and heavy metals. Here we describe fabrication of a novel helical-ribbon mixer dryer for transition from the current small-scale household cooking to equipment-driven sustainable production. Blood and rumen digesta mixed in a 3:1 ratio, having initial moisture of 85%, were dried at 90–110 °C for 3–4 h to attain 15.6% final moisture-containing organic fertilizer. Energy consumption and moisture extraction rate were 49.4 MJ per batch and 18.9 kg h⁻¹ respectively. Using this method, small abattoir owners could emerge as multi-product producers to enhance earnings while farmers could source the fertilizer locally for organic farming. The two activities can be complementary to each other and become a sustainable circular economy model. We applied a spreadsheet-based model for calculation of cash flow, breakeven point and conducted financial cost–benefit analysis on the projected operation of the dryer. Fertilizer production parallel with the meat trade should be profitable for slaughterhouse owners and farmers apart from generating local employment opportunities. Full article

Exosomes, the endosome-derived bilayered extracellular nanovesicles with their contribution in many aspects of cancer biology, have become one of the prime foci of research. Exosomes derived from various cells carry cargoes similar to their originator cells and their mode of generation is different compared to other extracellular vesicles. This review has tried to cover all aspects of exosome biogenesis, including cargo, Rab-dependent and Rab-independent secretion of endosomes and exosomal internalization. The bioactive molecules of the tumor-derived exosomes, by virtue of their ubiquitous presence and small size, can migrate to distal parts and propagate oncogenic signaling and epigenetic regulation, modulate tumor microenvironment and facilitate immune escape, tumor progression and drug resistance responsible for cancer progression. Strategies improvised against tumor-derived exosomes include suppression of exosome uptake, modulation of exosomal cargo and removal of exosomes. Apart from the protumorigenic role, exosomal cargoes have been selectively manipulated for diagnosis, immune therapy, vaccine development, RNA therapy, stem cell therapy, drug delivery and reversal of chemoresistance against cancer. However, several challenges, including in-depth knowledge of exosome biogenesis and protein sorting, perfect and pure isolation of exosomes, large-scale production, better loading efficiency, and targeted delivery of exosomes, have to be confronted before the successful implementation of exosomes becomes possible for the diagnosis and therapy of cancer. Full article

The current pandemic, caused by SARS-CoV-2 virus, is a severe challenge for human health and the world economy. There is an urgent need for development of drugs that can manage this pandemic, as it has already infected 19 million people and led to the death of around 711,277 people worldwide. At this time, in-silico studies are providing lots of preliminary data about potential drugs, which can be a great help in further in-vitro and in-vivo studies. Here, we have selected three polyphenolic compounds, mangiferin, glucogallin, and phlorizin. These compounds are isolated from different natural sources but share structural similarities and have been reported for their antiviral activity. The objective of this study is to analyze and predict the anti-protease activity of these compounds on SARS-CoV-2main protease (Mpro) and TMPRSS2 protein. Both the viral protein and the host protein play an important role in the viral life cycle, such as post-translational modification and viral spike protein priming. This study has been performed by molecular docking of the compounds using PyRx with AutoDock Vina on the two aforementioned targets chosen for this study, i.e., SARS-CoV-2 Mpro and TMPRSS2. The compounds showed good binding affinity and are further analyzed by (Molecular dynamic) MD and Molecular Mechanics Poisson-Boltzmann Surface Area MM-PBSA study. The MD-simulation study has predicted that these natural compounds will have a great impact on the stabilization of the binding cavity of the Mpro of SARS-CoV-2. The predicted pharmacokinetic parameters also show that these compounds are expected to have good solubility and absorption properties. Further predictions for these compounds also showed no involvement in drug-drug interaction and no toxicity. Full article

Atomically thin molybdenum disulfide (MoS₂), a member of the transition metal dichalcogenide (TMDC) family, has emerged as the prototypical two-dimensional (2D) semiconductor with a multitude of interesting properties and promising device applications spanning all realms of electronics and optoelectronics. While possessing inherent advantages over conventional bulk semiconducting materials (such as Si, Ge and III-Vs) in terms of enabling ultra-short channel and, thus, energy efficient field-effect transistors (FETs), the mechanically flexible and transparent nature of MoS₂ makes it even more attractive for use in ubiquitous flexible and transparent electronic systems. However, before the fascinating properties of MoS₂ can be effectively harnessed and put to good use in practical and commercial applications, several important technological roadblocks pertaining to its contact, doping and mobility (µ) engineering must be overcome. This paper reviews the important technologically relevant properties of semiconducting 2D TMDCs followed by a discussion of the performance projections of, and the major engineering challenges that confront, 2D MoS₂-based devices. Finally, this review provides a comprehensive overview of the various engineering solutions employed, thus far, to address the all-important issues of contact resistance (R_C), controllable and area-selective doping, and charge carrier mobility enhancement in these devices. Several key experimental and theoretical results are cited to supplement the discussions and provide further insight. Full article

Environmental and health safety of recycled slaughterhouse wastes-derived fertilizer and the produce obtained through its application is not well understood. Waste bovine blood and rumen digesta were mixed, cooked and sun-dried to obtain bovine-blood-and-rumen-digesta-mixture (BBRDM, NPK 30.36:1:5.75). 1.26 ± 0.18 log CFU mL⁻¹ fecal coliforms were recovered in BBRDM. E. coli O157:H7, Mycobacteria, Clostridium sp., Salmonella sp., Bacillus sp. and Brucella sp. were absent. No re-growth of pathogens was observed after 60 days storage in sealed bags and in the open. However, prions and viruses were not evaluated. Heavy metals (Pb, Cr, Cd, Cu, Zn, As, Ni, Mn) concentrations in BBRDM were within internationally permissible limits. BBRDM was applied for field cultivation of tomato during 2012–2013 and 2013–2014. Lycopene and nitrate contents of BBRDM-grown tomatoes were higher than Diammonium phosphate (DAP) + potash-grown tomatoes because BBRDM supplied 2.5 times more the amount of nitrogen than DAP (NPK 18:46:0) + potash (NPK 0:0:44). Heavy metals and nitrate/nitrite concentrations in tomatoes were within internationally acceptable limits. BBRDM-grown tomatoes showed no mutagenic activity in the Ames test. Sub-acute toxicity tests on Wistar rats fed with BBRDM-grown tomatoes did not show adverse clinical picture. Thus, no immediate environmental or health risks associated with BBRDM and the tomatoes produced were identified. Full article