Condensed Chromatin Behaves like a Solid on the Mesoscale In Vitro and in Living Cells.

The association of nuclear DNA with histones to form chromatin is essential for temporal and spatial control of eukaryotic genomes. In this study, we examined the physical state of condensed chromatin in vitro and in vivo. Our in vitro studies demonstrate that self-association of nucleosomal arrays under a wide range of solution conditions produces supramolecular condensates in which the chromatin is physically constrained and solid-like. By measuring DNA mobility in living cells, we show that condensed chromatin also exhibits solid-like behavior in vivo. Representative heterochromatin proteins, however, display liquid-like behavior and coalesce around the solid chromatin scaffold. Importantly, euchromatin and heterochromatin show solid-like behavior even under conditions that produce limited interactions between chromatin fibers. Our results reveal that condensed chromatin exists in a solid-like state whose properties resist external forces and create an elastic gel and provides a scaffold that supports liquid-liquid phase separation of chromatin binding proteins.

Efficient anode material derived from nutshells for bio-energy production in microbial fuel cell.

Biochar is a carbonaceous solid that is prepared through thermo-chemical decomposition of biomass under an inert atmosphere. The present study compares the performance of biochar prepared from Peanut shell, coconut shell and walnut shell in dual chamber microbial fuel cell. The physicochemical and electrochemical analysis of biochar reveals that prepared biochar is macroporous, amorphous, biocompatible, and electrochemically conductive. Polarization studies show that Peanut shell biochar (PSB) exhibited a maximum power density of 165 mW/m2 followed by Coconut shell biochar (CSB) Activated Charcoal (AC) and Walnut shell biochar (WSB). Enhanced power density of PSB was attributed to its surface area and suitable pore size distribution which proved conducive for biofilm formation. Furthermore, the high electrical capacitance of PSB improved the electron transfer between microbes and anode.

Emerging waste-to-wealth applications of fly ash for environmental remediation: A review.

The considerable increase in world energy consumption owing to rising global population, intercontinental transportation and industrialization has posed numerous environmental concerns. Particularly, in order to meet the required electricity supply, thermal power plants for electricity generation are widely used in many countries. However, an annually excessive quantity of waste fly ash up to 1 billion tones was globally discarded from the combustion of various carbon-containing feedstocks in thermoelectricity plants. About half of the industrially generated fly ash is dumped into landfills and hence causing soil and water contamination. Nonetheless, fly ash still contains many valuable components and possesses outstanding physicochemical properties. Utilizing waste fly ash for producing value-added products has gained significant interests. Therefore, in this work, we reviewed the current implementation of fly ash-derived materials, namely, zeolite and geopolymer as efficient adsorbents for the environmental treatment of flue gas and polluted water. Additionally, the usage of fly ash as a catalyst support for the photodegradation of organic pollutants and reforming processes for the corresponding wastewater remediation and H2 energy generation is thoroughly covered. In comparison with conventional carbon-based adsorbents, fly ash-derived geopolymer and zeolite materials reportedly exhibited greater heavy metal ions removal and reached the maximum adsorption capacity of about 150 mg g-1. As a support for biogas reforming process, fly ash could enhance the activity of Ni catalyst with 96% and 97% of CO2 and CH4 conversions, respectively.

Nanoparticle-based toxicity in perishable vegetable crops: Molecular insights, impact on human health and mitigation strategies for sustainable cultivation.

With the advancement of nanotechnology, the use of nanoparticles (NPs) and nanomaterials (NMs) in agriculture including perishable vegetable crops cultivation has been increased significantly. NPs/NMs positively affect plant growth and development, seed germination, plant stress management, and postharvest handling of fruits and vegetables. However, these NPs sometimes cause toxicity in plants by oxidative stress and excess reactive oxygen species production that affect cellular biomolecules resulting in imbalanced biological and metabolic processes in plants. Therefore, information about the mechanism underlying interactions of NPs with plants is important for the understanding of various physiological and biochemical responses of plants, evaluating phytotoxicity, and developing mitigation strategies for vegetable crops cultivation. To address this, recent morpho-physiological, biochemical and molecular insights of nanotoxicity in the vegetable crops have been discussed in this review. Further, factors affecting the nanotoxicity in vegetables and mitigation strategies for sustainable cultivation have been reviewed. Moreover, the bioaccumulation and biomagnification of NPs and associated phytotoxicity can cause serious effects on human health which has also been summarized. The review also highlights the use of advanced omics approaches and interdisciplinary tools for understanding the nanotoxicity and their possible use for mitigating phytotoxicity.

Novel synthesis of fluorescent carbon dots from bio-based Carica Papaya Leaves: Optical and structural properties with antioxidant and anti-inflammatory activities.

Fluorescent carbon dots (CDs) are prepared from a natural resource Carica Papaya Leaves, by sand bath method. The as-synthesized CDs optical and structural properties were characterized by UltraViolet-Visible, FT- IR, and fluorescence spectroscopy. Also the size, shape, and particle size distribution was studied using Transmission electron microscopy technique. These CDs were examined for biomedical applications like free radical scavenging activity using DPPH assay, antioxidant activity using phosphomolybdate assay, and in vitro anti-inflammatory activity using membrane stabilization protocol. The CDs exhibited excellent biological activities at lower concentrations and showed notable half-maximal effective concentration (EC50). The EC50 of free radical scavenging activity (27.6 µg/mL), antioxidant activity (23.00 µg/mL), and in vitro anti-inflammatory activity (15.52 µg/mL) signifies that CDs can be potential therapeutic agents.

Applicability of bio-synthesized nanoparticles in fungal secondary metabolites products and plant extracts for eliminating antibiotic-resistant bacteria risks in non-clinical environments.

The abundance of antibiotic-resistant bacteria in the prawn pond effluents can substantially impact the natural environment. The settlement ponds, which are the most common treatment method for farms wastewater, might effectively reduce the suspended solids and organic matter. However, the method is insufficient for bacterial inactivation. The current paper seeks to highlight the environmental issue associated with the distribution of antibiotic resistant bacteria (ARB) from prawn farm wastewater and their impact on the microbial complex community in the surface water which receiving these wastes. The inactivation of antibiotic-resistant bacteria in prawn wastewater is strongly recommended because the presence of antibiotic-resistant bacteria in the environment causes water pollution and public health issues. The nanoparticles are more efficient for bacterial inactivation. They are widely accepted due to their high chemical and mechanical stability, broad spectrum of radiation absorption, high catalytic activity, and high antimicrobial activity. Many studies have examined the use of fungi or plants extract to synthesis zinc oxide nanoparticles (ZnO NPs). It is evident from recent papers in the literature that green synthesized ZnO NPs from microbes and plant extracts are non-toxic and effective. ZnO NPs inactivate the bacterial cells as a function for releasing reactive oxygen species (ROS) and zinc ions. The inactivation of antibiotic-resistant bacteria tends to be more than 90% which exhibit strong antimicrobial behavior against bacterial species.

Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines.

Glioblastoma (GB) is a deadly and aggressive cancer of the CNS. Even with extensive resection and chemoradiotherapy, patient survival is still only 15 months. To maintain growth and proliferation, cancer cells require a high oxidative state. Curcumin, a well-known anti-inflammatory antioxidant, is a potential candidate for treatment of GB. To facilitate efficient delivery of therapeutic doses of curcumin into cells, we encapsulated the drug in surface-modified polyamidoamine (PAMAM) dendrimers. We studied the in vitro effectiveness of a traditional PAMAM dendrimer (100% amine surface, G4 NH2), surface-modified dendrimer (10% amine and 90% hydroxyl-G4 90/10-Cys), and curcumin (Cur)-encapsulated dendrimer (G4 90/10-Cys-Cur) on three species of glioblastoma cell lines: mouse-GL261, rat-F98, and human-U87. Using an MTT assay for cell viability, we found that G4 90/10-Cys-Cur reduced viability of all three glioblastoma cell lines compared to non-cancerous control cells. Under similar conditions, unencapsulated curcumin was not effective, while the non-modified dendrimer (G4 NH2) caused significant death of both cancerous and normal cells. By harnessing and optimizing the components of PAMAM dendrimers, we are providing a promising new route for delivering cancer therapeutics. Our results with curcumin suggest that antioxidants are good candidates for treating glioblastoma.

Use of Polyamidoamine Dendrimers in Brain Diseases.

Polyamidoamine (PAMAM) dendrimers are one of the smallest and most precise nanomolecules available today, which have promising applications for the treatment of brain diseases. Each aspect of the dendrimer (core, size or generation, size of cavities, and surface functional groups) can be precisely modulated to yield a variety of nanocarriers for delivery of drugs and genes to brain cells in vitro or in vivo. Two of the most important criteria to consider when using PAMAM dendrimers for neuroscience applications is their safety profile and their potential to be prepared in a reproducible manner. Based on these criteria, features of PAMAM dendrimers are described to help the neuroscience researcher to judiciously choose the right type of dendrimer and the appropriate method for loading the drug to form a safe and effective delivery system to the brain.

PAMAM Dendrimers Cross the Blood-Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice.

Drug delivery into the central nervous system (CNS) is challenging due to the blood-brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH2 and G4-NH2) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures. In vivo experiments involved transplantation of G4-90/10 into mice through (1) invasive intracranial injections into the striatum; and (2) less invasive carotid injections. The animals were sacrificed 24-h and 1-week post-transplantations and their brains were analyzed. In vivo experiments proved that the G4-90/10 can cross the BBB when injected through the carotid artery and localize within neurons and glial cells. The dendrimers were found to migrate through the corpus callosum 1-week post intracranial injection. Immunohistochemistry showed that the migrating cells are the dendrimer-infected glial cells. Overall, our results suggest that poly-amidoamine (PAMAM) dendrimers may be used as a minimally invasive means to deliver biomolecules for treating neurological diseases or disorders.

Integrated ternary nanocomposite of TiO2/NiO/reduced graphene oxide as a visible light photocatalyst for efficient degradation of o-chlorophenol.

This study investigated a novel approach for the synthesis of an integrated ternary nanocomposite which could act as a good photo-catalyst under visible light irradiation for the removal of organic pollutants from aqueous environments. The photo-catalyst included nickel oxide (NiO) as a dopant, and reduced graphene oxide (RGO) as a good carbon basal support for enhancement of the photo-catalytic activity of TiO2. Under irradiation with visible light, the ternary nanocomposite (TiO2/NiO-RGO) system generates e(-)/h(+) pairs, and then reacts with H2O and O2(-) molecules to produce oxy-radicals which can be used for the mineralization of o-chlorophenol from aqueous solution. The characteristic of all photo-catalysts were investigated by UV-Vis analysis, with surface area and pore size measurements by Brunauer-Emmett-Teller (BET), crystallinity by X-ray diffraction (XRD), elemental composition by X-ray photoelectron spectroscopy (XPS), and morphology by scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX). The functional groups were measured by Fourier transform infrared (FT-IR) spectroscopy before and after o-chlorophenol degradation. TiO2/NiO-RGO was capable of achieving 88.4% photo-degradation of 100 mg/L o-chlorophenol (100 mL) within 8 h with addition of 0.01% H2O2 under visible light irradiation at pH 6.5. The photo-degradation followed a pseudo-first-order reaction. The TiO2/NiO-RGO nanocomposite retained its high removal efficiency, even after four photo-catalytic cycles.

Rapid photo-degradation of 2-chlorophenol under visible light irradiation using cobalt oxide-loaded TiO2/reduced graphene oxide nanocomposite from aqueous media.

The photocatalytic removal of 2-chlorophenol (2-CP) from water environment was investigated by TiO2-RGO-CoO. Cobalt oxide-loaded TiO2 (TiO2-CoO) supported with reduced graphene oxide (RGO) was synthesized using a sol-gel method and then annealed at 500 °C for 5 min. The material characteristics were analyzed by UV-Vis analysis, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. Incorporation of cobalt oxide and RGO into the TiO2 system (TiO2-RGO-CoO) lowered the band gap energy to 2.83 eV, which greatly enhanced the visible light absorption. The TiO2-RGO-CoO photocatalyst showed complete removal of 20 mg/L 2-CP within 8 h with the addition of 0.01% H2O2 under 100 W visible light irradiation. The photo-degradation efficiency of 2-CP (10 mg/L) was 35.2, 48.9, 58.9 and 98.2% for TiO2, TiO2-RGO, TiO2-CoO and TiO2-RGO-CoO, respectively, in the presence of visible light irradiation at solution pH of 6.0. The TiO2-RGO-CoO photocatalyst retained its high removal efficiency even after five photocatalytic cycles.

Adsorptive/photo-catalytic process for naphthalene removal from aqueous media using in-situ nickel doped titanium nanocomposite.

The present study investigates the synthesis and characterization of in-situ nickel doped titanium nanocomposite (TiO2/NiO) use as an adsorbent and a photo-catalyst for naphthalene removal from aqueous phase. Nickel-titanium nanocomposites were synthesized by using an in-situ process for the nickel doping and further calcined at 600 °C for 6 h to produce the desired TiO2/NiO nanocomposite, which was then characterized by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and UV-Vis analysis before and after naphthalene removal. The removal of naphthalene was explored with effect of pH, time and initial concentration of naphthalene (2-25 mg/L) in the presence of dark and light phases. Naphthalene removal tests were conducted under both batch and continuous flow conditions. A special column without any channeling problem was successfully designed for the removal of naphthalene by continuous flow process in the presence of visible light source. The removal was maximized at pH 6.5. The maximum amount of naphthalene removed by TiO2/NiO(0.1) nanocomposite in the presence of visible light phase was 322.1 mg/g, which was 2.5 times greater than that of the parent TiO2. The removal of naphthalene obtained during the breakthrough analysis was consistent with the batch equilibrium data.

Analysis of polyamidoamine dendrimers by isoelectric focusing.

Polyamidoamine dendrimers have been studied extensively for their potential applications in nanomedicine. Their uses as imaging, drug, and nucleic acid delivery agents are nearing clinical trials. As such, characterization of polyamidoamine dendrimers and their nano-devices is of immense importance for monitoring the efficiency of their synthesis, purity, and quality control of manufactured products as well as their in vivo behavior. We report here the analysis of polyamidoamine dendrimers possessing various cores and surface groups with a simple and inexpensive isoelectric focusing method. The isoelectric points of the dendrimers were readily determined from a calibration plot generated by running proteins with known pI values. The isoelectric points for various surface-modified polyamidoamine dendrimers ranged from 4 to 9. Polyamidoamine dendrimers possessing terminal hydroxyl groups gave a pI > 7, while those with terminal carboxyl groups exhibit a pI < 7. Generation number and cores of the dendrimers did not significantly affect their isoelectric points. Isoelectric focusing thus offers another important tool for characterizing these nanomolecules.

Investigating the potential of delignified rice husk as a carbon-rich resource for extracting glucose and its utilization in biocement production through fungal isolates.

Burning rice straw is now a significant issue faced by different regions in India, as its burning releases harmful gases, mainly carbon dioxide. Various techniques are now in trend to utilize the rice straw, e.g., producing compressed natural gas using rice straw, bioethanol, etc., as a substrate for various microorganisms. A high quantity of non-utilized rice husk generates more ideas for its proper utilization. The cellulose, hemicellulose, and lignin found in rice straws can be a fungi growth medium. In this research, the delignification of rice husk is done by acid (2% and 4% H2SO4) and alkali (2% and 4% NaOH) at 121 °C at 103 kPa for 1 h to obtain crude carbon source which is further utilized for biomineralization. The glucose is subjected to qualitative and quantitative analysis using Molisch's and Dinitro salicylic tests. The delignification process showed a positive outcome when 2% H2SO4 is utilized maximum yield of 5.9 ug/ml free sugar concentration. Representing the highest glucose yield compared to the experiment's other acid and base substances used. Various techniques such as field emission-scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and Fourier transformed infra-red (FTIR) spectroscopy are employed to examine surface and chemical alterations. The 2% H2SO4 pretreated rice husk is utilized for microbial-induced calcite precipitation using fungal isolates S1 (3), S1 (18), and S4 (1). The calcite and vaterite produced by biomineralization are confirmed using XRD for fungal isolates namely, S1 (3), S1 (18), and S4 (1) having percentage crystallinity of 59%, 46.428%, and 62.69% percentage crystallinity respectively.

Microenvironment shapes small-cell lung cancer neuroendocrine states and presents therapeutic opportunities.

Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the cell-extrinsic drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the TME exhibit substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAFs) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Our work provides a comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLC's adaptable nature, opening possibilities for reprogramming the TME-tumor communications that shape SCLC tumor states.

Copper-granule-catalyzed microwave-assisted click synthesis of polyphenol dendrimers.

Syringaldehyde- and vanillin-based antioxidant dendrimers were synthesized via microwave-assisted alkyne-azide 1,3-dipolar cycloaddition using copper granules as a catalyst. The use of Cu(I) as a catalyst resulted in copper contaminated dendrimers. To produce copper-free antioxidant dendrimers for biological applications, Cu(I) was substituted with copper granules. Copper granules were ineffective at both room temperature and under reflux conditions (<5% yield). However, they were an excellent catalyst when dendrimer synthesis was performed under microwave irradiation, giving yields up to 94% within 8 h. ICP-mass analysis of the antioxidant dendrimers obtained with this method showed virtually no copper contamination (9 ppm), which was the same as the background level. The synthesized antioxidants, free from copper contamination, demonstrated potent radical scavenging with IC50 values of less than 3 µM in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In comparison, dendrimers synthesized from Cu(I)-catalyzed click chemistry showed a high level of copper contamination (4800 ppm) and no detectable antioxidant activity.

Lead sorption onto acrylamide modified titanium nanocomposite from aqueous media.

The purpose of this study was to investigate the adsorption of lead (Pb(II)) onto acrylamide (AM) doped TiO2 nanocomposites (Ti-AM) using batch techniques for evaluation of isothermal and kinetic properties. Chemical, structural and textural characteristics of the material were determined by FTIR, XPS, XRD, SEM and EDAX analysis. XPS results showed that a change in oxidation state occurred due to lead adsorption. The adsorption conditions for the adsorbent were optimized by varying several experimental parameters, i.e., contact time, initial lead concentration, adsorbent dose, pH, and electrolyte amount of the solution. The adsorption data were modeled using both the Langmuir and Freundlich isotherms. The maximum adsorption capacity using Langmuir isotherm (qmax) for the nanocomposite was found to be 476.19 mg g(-1). Adsorption showed pseudo-second-order kinetics with a rate constant of 8.7 × 10(-4) and 1.2 × 10(-4) g mg(-1)min(-1) at 100 and 500 mg L(-1) initial Pb(II) concentrations, respectively. Acrylamide concentration in nanocomposite synthesis up to 1 g had greater influence on the sorption of lead. The most favorable pH for the adsorption was pH 5.5. With increasing concentrations of three electrolytes (NaCl, Na2SO4 and Na2CO3) from 0.01 to 1.0 M Pb(II), the lead removal decreases from 76.3 to 32.8 mg g(-1), from 97.4 to 68.7 mg g(-1), and from 98.8 to 72.5 mg g(-1), respectively. Further, the Ti-AM nanocomposite is amenable to efficient regeneration by a 0.05 N HCl solution for repeated (up to six cycles) use without any significant capacity loss, making this approach very economical.

The dark side of circular RNA, a new driver of genome instability.

Circular RNAs (circRNAs) are covalently closed RNA molecules whose functions are still largely uncharacterized. In the July issue of Cancer Cell, Conn et al.1 demonstrate that circRNA can bind cognate DNA loci, forming circRNA-DNA hybrids (circR loops), driving genetic rearrangements of MLL/KMT2A, which are associated with the most aggressive acute leukemias.

Recent Developments in the Synthesis and Anticancer Activity of Indole and Its Derivatives.

Heterocyclic compounds are a class of compounds that is deeply intertwined with biological processes and is found in about 90% of commercially available medicines. They serve a critical function in medicinal chemistry and are focused in the field of medication development for their intensive research due to their broad variety of biological effects because of their intriguing molecular architecture, such as indoles are good candidates for drug development. It is a bicyclic structure consisting of a six-membered benzene ring fused to a five-membered pyrrole ring with several pharmacophores that yield a library of different lead compounds. Human cancer cells have been demonstrated to be inhibited by indoles in the development of new anticancer medicines. This is the first comprehensive review to focus on current methodologies for incorporating indole moiety, with their mechanistic targets as anticancer drugs, in order to shed light on the logical development of indole-based anticancer treatment options with high efficacy. This compiled data may serve as a benchmark for modifying existing ligands in order to design novel potent molecules through excellent yield synthesis techniques.

Role of Tyrosine Kinases and their Inhibitors in Cancer Therapy: A Comprehensive Review.

BACKGROUND: Cancer has been recognized as one of the non-communicable diseases with an increasing number of new cases, higher morbidity, and higher mortality rates at the global level. Thus, there is non-stop search for novel targets and small molecules to improve the chemotherapeutic outcomes concerning potency, selectivity, efficiency, affinity, ADMET, etc. Among anticancer therapeutic targets, tyrosine kinase has been documented well and approved as an important target with the development of various clinically used drugs. There are several structurally diverse small molecules in different preclinical and clinical stages of development that act by affecting tyrosine kinases in cancerous cells. Here, we have summarized different potent molecules acting against tyrosine kinases that can be considered as anticancer agents. OBJECTIVE: The current review focused on structural aspects of different chemical agents for inhibition of tyrosine kinases as anticancer agents. METHODS: The present study provides a summarized review of published information on tyrosine kinase inhibitors, their binding pattern, potencies, and structure-activity relationships. The review also highlighted the structural aspects of the interaction between inhibitors and amino acid residues of tyrosine kinases. Moreover, it also provided a summary of different types of cancers and the currently available options for treatment. RESULTS: Several studies are being conducted for the inhibition of different tyrosine kinases using small molecules for the treatment of cancer. Tyrosine kinases have been reported involving in routine cellular functions, growth, and division of cells through different pathways which depend on phosphorylation. The overexpression and uncontrolled activity of tyrosine kinases have been identified as an important feature of cancerous cells. Thus, various small molecules have been reported which inhibit tyrosine kinases to block the growth and division of cancer cells. Here, more than 30 highly potent inhibitors of tyrosine kinases are summarised, which consist of pyrimidine, pyrazole, triazine, quinazoline, quinoline, pyrazine, chromene, etc. rings as a basic skeleton with different substituents. CONCLUSION: Inhibition of tyrosine kinases by different small molecules is an approved strategy for the development of novel anticancer agents. Several published reports have mentioned the characteristics of the different binding sites and crucial residues in tyrosine kinases for the design of novel molecular inhibitors. However, selectivity is an important criterion for the development of chemotherapeutic agents due to the existence of approximately 30 families of tyrosine kinases.