Methane sources from waste and natural gas sectors detected in Pune, India, by concentration and isotopic analysis.

Methane (CH4) is a potent greenhouse gas and also plays a significant role in tropospheric chemistry. High-frequency (sub-hourly) measurements of CH4 and carbon isotopic ratio (δ13CH4) have been conducted at Pune (18.53°N, 73.80°E), an urban environment in India, during 2018-2020. High CH4 concentrations were observed, with a mean of 2100 ± 196 ppb (1844-2749 ppb), relative to marine background concentrations. The δ13CH4 varied between -45.11 and -50.03 ‰ for the entire study period with an average of -47.41 ± 0.94 ‰. The diurnal variability of CH4 typically showed maximum values in the morning (08:00-09:00 local time) and minimum in the afternoon (15:00 local time). The deepest diurnal amplitude of ~500 ppb was observed during winter (December-February), which was reduced to less than half, ~200 ppb, during the summer (March-May). CH4 concentration at Pune showed a strong seasonality (470 ppb), much higher than that at Mauna Loa, Hawaii. On the other hand, δ13CH4 records did not show distinct seasonality at Pune. The δ13CH4 values revealed that the significant sources of CH4 in Pune were from the waste sector (enhanced during the monsoon season; signature of depleted δ13CH4), followed by the natural gas sector with a signature of enriched δ13CH4. Our analysis of Covid-19 lockdown (April to May 2020) effect on the CH4 variability showed no signal in the CH4 variability; however, the isotopic analysis indicated a transient shift in the CH4 source to the waste sector (early summer of 2020).

Expression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids.

Microglia play a role in the emergence and preservation of a healthy brain microenvironment. Dysfunction of microglia has been associated with neurodevelopmental and neurodegenerative disorders. Investigating the function of human microglia in health and disease has been challenging due to the limited models of the human brain available. Here, we develop a method to generate functional microglia in human cortical organoids (hCOs) from human embryonic stem cells (hESCs). We apply this system to study the role of microglia during inflammation induced by amyloid-ß (Aß). The overexpression of the myeloid-specific transcription factor PU.1 generates microglia-like cells in hCOs, producing mhCOs (microglia-containing hCOs), that we engraft in the mouse brain. Single-cell transcriptomics reveals that mhCOs acquire a microglia cell cluster with an intact complement and chemokine system. Functionally, microglia in mhCOs protect parenchyma from cellular and molecular damage caused by Aß. Furthermore, in mhCOs, we observed reduced expression of Aß-induced expression of genes associated with apoptosis, ferroptosis, and Alzheimer's disease (AD) stage III. Finally, we assess the function of AD-associated genes highly expressed in microglia in response to Aß using pooled CRISPRi coupled with single-cell RNA sequencing in mhCOs. In summary, we provide a protocol to generate mhCOs that can be used in fundamental and translational studies as a model to investigate the role of microglia in neurodevelopmental and neurodegenerative disorders.

Graphene nanofiber composites for enhanced neuronal differentiation of human mesenchymal stem cells.

Aim: To differentiate mesenchymal stem cells into functional dopaminergic neurons using an electrospun polycaprolactone (PCL) and graphene (G) nanocomposite. Methods: A one-step approach was used to electrospin the PCL nanocomposite, with varying G concentrations, followed by evaluating their biocompatibility and neuronal differentiation. Results: PCL with exiguous graphene demonstrated an ideal nanotopography with an unprecedented combination of guidance stimuli and substrate cues, aiding the enhanced differentiation of mesenchymal stem cells into dopaminergic neurons. These newly differentiated neurons were seen to exhibit unique neuronal arborization, enhanced intracellular Ca2+ influx and dopamine secretion. Conclusion: Having cost-effective fabrication and room-temperature storage, the PCL-G nanocomposites could pave the way for enhanced neuronal differentiation, thereby opening a new horizon for an array of applications in neural regenerative medicine.

Manipulating Extracellular Matrix Organizations and Parameters to Control Local Cancer Invasion.

Metastasis contributes to over 90 percent of cancer mortalities and may be influenced by the extracellular matrix (ECM). ECM microenvironments differ in matrix organization, cell-matrix adhesions, and fiber rigidity, which may affect cancer migration and, thus, should be investigated. To understand the interactions between cancer cells and the ECM, we simulate local invasion through ECM organizations of varying determinants. Randomly curved organizations of normal ovarian stroma exhibit minimal local invasion. In contrast, wave-like and parallel linear structures in reorganized ECM organizations provide contact guidance, which increases cancer invasiveness. ECM organizations with strong cell-matrix attachments generate cell pseudopodia, which aid in increasing invasion rate, while weaker attachments prevent the cells from attaching to the fibers and forming pseudopodia, limiting local invasion. ECM organizations with rigid fibers elongate the cell body, allowing them to form cell protrusions and spread rapidly. Conversely, soft fibers stimulate cell rounding and limit migration. Optimizing cell-matrix adhesions and fiber rigidity results in below 10 percent local invasion and reinforces the importance of using computational modeling to discover novel approaches to restricting cancer movement.

A Computational Approach for Understanding the Interactions between Graphene Oxide and Nucleoside Diphosphate Kinase with Implications for Heart Failure.

During a heart failure, an increased content and activity of nucleoside diphosphate kinase (NDPK) in the sarcolemmal membrane is responsible for suppressing the formation of the second messenger cyclic adenosine monophosphate (cAMP)-a key component required for calcium ion homeostasis for the proper systolic and diastolic functions. Typically, this increased NDPK content lets the surplus NDPK react with a mutated G protein in the beta-adrenergic signal transduction pathway, thereby inhibiting cAMP synthesis. Thus, it is thus that inhibition of NDPK may cause a substantial increase in adenylate cyclase activity, which in turn may be a potential therapy for end-stage heart failure patients. However, there is little information available about the molecular events at the interface of NDPK and any prospective molecule that may potentially influence its reactive site (His118). Here we report a novel computational approach for understanding the interactions between graphene oxide (GO) and NDPK. Using molecular dynamics, it is found that GO interacts favorably with the His118 residue of NDPK to potentially prevent its binding with adenosine triphosphate (ATP), which otherwise would trigger the phosphorylation of the mutated G protein. Therefore, this will result in an increase in cAMP levels during heart failure.

New Antimony Selenide/Nickel Oxide Photocathode Boosts the Efficiency of Graphene Quantum-Dot Co-Sensitized Solar Cells.

A novel assembly of a photocathode and a photoanode is investigated to explore their complementary effects in enhancing the photovoltaic performance of a quantum-dot solar cell (QDSC). While p-type nickel oxide (NiO) has been used previously, antimony selenide (Sb2Se3) has not been used in a QDSC, especially as a component of a counter electrode (CE) architecture that doubles as the photocathode. Here, near-infrared (NIR) light-absorbing Sb2Se3 nanoparticles (NPs) coated over electrodeposited NiO nanofibers on a carbon (C) fabric substrate was employed as the highly efficient photocathode. Quasi-spherical Sb2Se3 NPs, with a band gap of 1.13 eV, upon illumination, release photoexcited electrons in addition to other charge carriers at the CE to further enhance the reduction of the oxidized polysulfide. The p-type conducting behavior of Sb2Se3, coupled with a work function at 4.63 eV, also facilitates electron injection to polysulfide. The effect of graphene quantum dots (GQDs) as co-sensitizers as well as electron conduits is also investigated in which a TiO2/CdS/GQDs photoanode structure in combination with a C-fabric CE delivered a power-conversion efficiency (PCE) of 5.28%, which is a vast improvement over the 4.23% that is obtained by using a TiO2/CdS photoanode (without GQDs) with the same CE. GQDs, due to a superior conductance, impact efficiency more than Sb2Se3 NPs do. The best PCE of a TiO2/CdS/GQDs-nS2-/Sn2--Sb2Se3/NiO/C-fabric cell is 5.96% (0.11 cm2 area), which, when replicated on a smaller area of 0.06 cm2, is seen to increase dramatically to 7.19%. The cell is also tested for 6 h of continuous irradiance. The rationalization for the channelized photogenerated electron movement, which augments the cell performance, is furnished in detail in these studies.

Nanoformulated water-soluble paclitaxel to enhance drug efficacy and reduce hemolysis side effect.

Surgery, chemotherapy, and radiotherapy are the three top cancer treatment modalities. Paclitaxel (PTX) is one of the most widely used chemotherapy drugs. However, its clinical applications have been significantly limited due to: (i) serious hemolysis effect of currently available commercial paclitaxel formulations and (ii) its water insolubility. An easy way to deliver paclitaxel by a new nanocarrier system using pluronic copolymers of P123/F68 and Sorbitan monopalmitate (Span 40) was reported in our previous research article. The characterization of the formulation and analysis of drug release and cellular uptake were also presented. In this article, we reported discoveries of our follow-up in vivo antitumor and in vitro hemolytic study discoveries. The experimental results showed that the nanoformulated PTX achieved much better tumor suppression performance while reducing hemolysis side effects. This newly formulated drug can significantly improve patient outcomes in cancer chemotherapy.

Interactions between avidin and graphene for development of a biosensing platform.

Fundamental understanding of interactions at the interface of biological molecules, such as proteins, and nanomaterials is crucial for developing various biocompatible hybrid materials and biosensing platforms. Biosensors comprising of graphene-based conductive nanomaterials offer the advantage of higher sensitivity and reliable diagnosis mainly due to their superior specific surface area and ballistic conductivity. Furthermore, conductive nanocomposite structures that immobilize proteins can synergize the properties of both transducers and molecular recognition elements improving the performance of the biosensing device. Here we report for the first time, using a combined molecular dynamics simulations and experimental approach, the interactions between avidin and graphene for the development of a sensing platform that can be used for the detection of biological macromolecules such as mismatch repair proteins through biotinylated DNA substrates. We find that the interactive forces between avidin and graphene are mainly hydrophobic, along with some van der Waals, electrostatic and hydrogen bonding interactions. Notably, the structure and function of the avidin molecule are largely preserved after its adsorption on the graphene surface. The MD results agree well with scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS) analysis of avidin immobilized on a graphenated polypyrrole (G-PPy) conductive nanocomposite confirming the adsorption of avidin on graphene nanoplatelets as observed from the Fourier-transform infrared spectroscopy (FTIR).

Using Gold Nanoparticles as Delivery Vehicles for Targeted Delivery of Chemotherapy Drug Fludarabine Phosphate to Treat Hematological Cancers.

Nanotechnology is an emerging paradigm for creating functional nanoscale materials for various biomedical applications. In this study, a new nanotechnology-based drug delivery method was developed using gold nanoparticles (GNPs) as a delivery vehicle to reduce adverse drug side effects. Fludarabine Phosphate is a commercial chemotherapy drug used in cancer treatment, and has ability to kill various cancer cells. KG-1 cell, a type of acute cancer leukemia cell, was selected as a proof-of-concept target in this study. Due to the small size of GNPs, they can help Fludarabine Phosphate enter cancer cells more efficiently and better interfere with DNA synthesis in the cancer cells. To enhance targeting ability, folic acid molecules were also covalently linked to GNPs, resulting in GNP-Fludarabine-folic acid (GNP-F/f). Compared to treatments with GNP-F or drugs on its own (Fludarabine Phosphate), the GNP-F/f achieves much improved cell-killing effects. The UV-Vis spectra results also revealed that the drugs had successfully bonded covalently to the GNPs. The higher cell-killing efficiency of GNP-F/f compared with GNP-Fludarabine (GNP-F) or drugs on their own further validates the effectiveness of both the vectors (GNPs) and folic acid in enhancing the drug delivery to the cancer cells. The MTT viability tests showed that the GNPs had no cytotoxicity.

Cytogenetic evaluation of functionalized single-walled carbon nanotube in mice bone marrow cells.

With their unique structure and physicochemical properties, single\-walled carbon nanotubes (SWCNTs) have many potential new applications in medicine and industry. However, there is lack of detailed information concerning their impact on human health and the environment. The aim of this study was to assess the effects, after intraperitoneal injection of functionalized SWCNTs (f-SWCNT) on the induction of reactive oxygen species (ROS), frequency of structural chromosomal aberrations (SCA), frequency of micronuclei induction, mitotic index, and DNA damage in Swiss-Webster mice. Three doses of f-SWCNTs (0.25, 0.5, and 0.75 mg/kg) and two controls (negative and positive) were administered to mice, once a day for 5 days. Bone marrow and peripheral blood samples were collected 24 h after the last treatment following standard protocols. F-SWCNT exposure significantly enhanced ROS, increased (p < 0.05) the number of SCA and the frequency of micronucleated cells, increased DNA damage, and decreased the mitotic index in exposed groups compared to negative control. The scientific findings reported here suggest that purified f-SWCNT have the potential to induce oxidative stress mediated genotoxicity in Swiss-Webster mice at higher level of exposure. Further characterization of their systemic toxicity, genotoxicity, and carcinogenicity is also essential. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1091-1102, 2016.

Synthesis and Electrochemical Analysis of Algae Cellulose-Polypyrrole-Graphene Nanocomposite for Supercapacitor Electrode.

A novel nanocomposite has been developed using extracted cellulose from marine algae coated with conductive polypyrrole and graphene nanoplateletes. The nanocomposite fabricated via in situ polymerization was used as an electrode for a supercapacitor device. The nanocomposite material has been electrochemically characterized using cyclic voltammetry to test its potential to super-capacitive behavior. The specific capacitance of polypyrrole-graphene-cellulose nanocomposite as calculated from cyclic voltammetry curve is 91.5 Fg-1 at the scan rate 50 mV s-1. Transmission electron microscope images show the polymerized polypyrrole -graphene coated cellulosic nanofibers. Scanning electron microscope images reveal an interesting "necklace" like beaded morphology on the cellulose fibers. It is observed that the necklace like structure start to disintegrate with the increase in graphene concentration. The open circuit voltage of the device with polypyrrole-graphene-cellulose electrode was found to be around 225 mV and that of the polypyrrole-cellulose device is only 53 mV without graphene. The results suggest marked improvement in the performance of the nanocomposite supercapacitor device upon graphene inclusion.

Hybrid Electrodes by In-Situ Integration of Graphene and Carbon-Nanotubes in Polypyrrole for Supercapacitors.

Supercapacitors also known as electrochemical capacitors, that store energy via either Faradaic or non-Faradaic processes, have recently grown popularity mainly because they complement, and can even replace, conventional energy storage systems in variety of applications. Supercapacitor performance can be improved significantly by developing new nanocomposite electrodes which utilizes both the energy storage processes simultaneously. Here we report, fabrication of the freestanding hybrid electrodes, by incorporating graphene and carbon nanotubes (CNT) in pyrrole monomer via its in-situ polymerization. At the scan rate of 5 mV s(-1), the specific capacitance of the polypyrrole-CNT-graphene (PCG) electrode film was 453 F g(-1) with ultrahigh energy and power density of 62.96 W h kg(-1) and 566.66 W kg(-1) respectively, as shown in the Ragone plot. A nanofibrous membrane was electrospun and effectively used as a separator in the supercapacitor. Four supercapacitors were assembled in series to demonstrate the device performance by lighting a 2.2 V LED.

Structure of collagen-glycosaminoglycan matrix and the influence to its integrity and stability.

Glycosaminoglycan (GAG) is a chain-like disaccharide that is linked to polypeptide core to connect two collagen fibrils/fibers and provide the intermolecular force in Collagen-GAG matrix (C-G matrix). Thus, the distribution of GAG in C-G matrix contributes to the integrity and mechanical properties of the matrix and related tissue. This paper analyzes the transverse isotropic distribution of GAG in C-G matrix. The angle of GAGs related to collagen fibrils is used as parameters to qualify the GAGs isotropic characteristic in both 3D and 2D rendering. Statistical results included that over one third of GAGs were perpendicular directed to collagen fibril with symmetrical distribution for both 3D matrix and 2D plane cross through collagen fibrils. The three factors tested in this paper: collagen radius, collagen distribution, and GAGs density, were not statistically significant for the strength of Collagen-GAG matrix in 3D rendering. However in 2D rendering, a significant factor found was the radius of collagen in matrix for the GAGs directed to orthogonal plane of Collagen-GAG matrix. Between two cross-section selected from Collagen-GAG matrix model, the plane cross through collagen fibrils was symmetrically distributed but the total percentage of perpendicular directed GAG was deducted by decreasing collagen radius. There were some symmetry features of GAGs angle distribution in selected 2D plane that passed through space between collagen fibrils, but most models showed multiple peaks in GAGs angle distribution. With less GAGs directed to perpendicular of collagen fibril, strength in collagen cross-section weakened. Collagen distribution was also a factor that influences GAGs angle distribution in 2D rendering. True hexagonal collagen packaging is reported in this paper to have less strength at collagen cross-section compared to quasi-hexagonal collagen arrangement. In this work focus is on GAGs matrix within the collagen and its relevance to anisotropy.

Graphene oxide as a quencher for fluorescent assay of amino acids, peptides, and proteins.

Understanding the interaction between graphene oxide (GO) and the biomolecules is fundamentally essential, especially for disease- and drug-related peptides and proteins. In this study, GO was found to strongly interact with amino acids (tryptophan and tyrosine), peptides (Alzheimer's disease related amyloid beta 1-40 and type 2 diabetes related human islet amyloid polypeptide), and proteins (drug-related bovine and human serum albumin) by fluorescence quenching, indicating GO was a universal quencher for tryptophan or tyrosine related peptides and proteins. The quenching mechanism between GO and tryptophan (Trp) or tyrosine (Tyr) was determined as mainly static quenching, combined with dynamic quenching (Förster resonance energy transfer). Different quenching efficiency between GO and Trp or Tyr at different pHs indicated the importance of electrostatic interaction during quenching. Hydrophobic interaction also participated in quenching, which was proved by the presence of nonionic amphiphilic copolymer Pluronic F127 (PF127) in GO dispersion. The strong hydrophobic interaction between GO and PF127 efficiently blocked the hydrophobic interaction between GO and Trp or Tyr, lowering the quenching efficiency.

Computer assisted detection of liver neoplasm (CADLN).

To date, radiologists evaluate neoplasm images manually. Currently there is wide spread attention for developing image processing modules to detect and measure early stage neoplasm growth in liver. We report the fundamentals associated with the development of a multifunctional image processing algorithm useful to measure early growth of neoplasm and the volume of liver. Using CADLN, a radiologist will be able to compare computer generated volumetric data in serial imaging of the patients over time, that eventually will enable assessing progression or regression of neoplasm growth and help in treatment planning.