Tumor recurrence remains the main reason for breast cancer-associated mortality, and there are unmet clinical demands for the discovery of new biomarkers and development of treatment solutions to ...benefit patients with breast cancer at high risk of recurrence. Here we report the identification of chromosomal copy-number amplification at 1q21.3 that is enriched in subpopulations of breast cancer cells bearing characteristics of tumor-initiating cells (TICs) and that strongly associates with breast cancer recurrence. Amplification is present in ∼10-30% of primary tumors but in more than 70% of recurrent tumors, regardless of breast cancer subtype. Detection of amplification in cell-free DNA (cfDNA) from blood is strongly associated with early relapse in patients with breast cancer and could also be used to track the emergence of tumor resistance to chemotherapy. We further show that 1q21.3-encoded S100 calcium-binding protein (S100A) family members, mainly S100A7, S100A8, and S100A9 (S100A7/8/9), and IL-1 receptor-associated kinase 1 (IRAK1) establish a reciprocal feedback loop driving tumorsphere growth. Notably, this functional circuitry can be disrupted by the small-molecule kinase inhibitor pacritinib, leading to preferential impairment of the growth of 1q21.3-amplified breast tumors. Our study uncovers the 1q21.3-directed S100A7/8/9-IRAK1 feedback loop as a crucial component of breast cancer recurrence, serving as both a trackable biomarker and an actionable therapeutic target for breast cancer.
A combination of measurements using photoelectron spectroscopy and calculations using density functional theory (DFT) was applied to compare the detailed electronic structure of the organolead halide ...perovskites CH3NH3PbI3 and CH3NH3PbBr3. These perovskite materials are used to absorb light in mesoscopic and planar heterojunction solar cells. The Pb 4f core level is investigated to get insight into the chemistry of the two materials. Valence level measurments are also included showing a shift of the valence band edges where there is a higher binding energy of the edge for the CH3NH3PbBr3 perovskite. These changes are supported by the theoretical calculations which indicate that the differences in electronic structure are mainly caused by the nature of the halide ion rather than structural differences. The combination of photoelectron spectroscopy measurements and electronic structure calculations is essential to disentangle how the valence band edge in organolead halide perovskites is governed by the intrinsic difference in energy levels of the halide ions from the influence of chemical bonding.
The present study explicitly evaluated the genetic structure of Aedes aegypti Linn, the vector of dengue, chikungunya, and Zika viruses, across different geo-climatic zones of India and also ...elucidated the impact of ecological and topographic factors. After data quality checks and removal of samples with excess null alleles, the final analysis was performed on 589 individual samples using 10 microsatellite markers. Overall findings of this study suggested that, Ae. aegypti populations are highly diverse with moderate genetic differentiation between them. Around half of the populations (13 out of 22) formed two genetic clusters roughly associated with geographical regions. The remaining nine populations shared genetic ancestries with either one or both of the clusters. A significant relationship between genetic and geographic distance was observed, indicating isolation by distance. However, spatial autocorrelation analysis predicted the signs of long-distance admixture. Post-hoc environmental association analysis showed that 52.7% of genetic variations were explained by a combination of climatic and topographic factors, with latitude and temperature being the best predictors. This study indicated that though overall genetic differentiation among Ae. aegypti populations across India is moderate (Fst = 0.099), the differences between the populations are developing due to the factors associated with geographic locations. This study improves the understanding of the Ae. aegypti population structure in India that may assist in predicting mosquito movements across the geo-climatic zones, enabling effective control strategies and assessing the risk of disease transmission.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bioelectrochemical systems (BESs) are unique systems capable of converting chemical energy into electrical energy (and vice-versa) while employing microbes as catalysts. Such organic wastes including ...low-strength wastewaters and lignocellulosic biomass were converted into electricity with microbial fuel cells (MFCs). Likewise, electrical energy was used to produce hydrogen in microbial electrolysis cells (MECs) or other products including caustic and peroxide. BES were also designed to recover nutrients, metals or removal of recalcitrant compounds. Moreover, photosynthetic micro-organisms as well as higher plants were implemented to use solar energy for electricity generation. The diversity on microbial and enzymatic catalysts offered by nature allows a plurality of potential applications. As compared to conventional fuel cells, BESs operate under relatively mild conditions and do not use expensive precious metals as catalysts. The recently discovered microbial electrosynthesis (MES) of high-value chemicals has greatly expanded the horizon for BES. Newer concepts in application as well as development of alternative materials for electrodes, separators, catalysts along with innovative designs have made BES very promising technology. This article discusses the recent developments that have been made in BESs so far, with the emphasis on their various applications beyond electricity generation and resulting performances as well as existing limitations.
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•Bioelectrochemical systems (BESs) are emerging rapidly with diverse applications.•Bioanode and biocathode performs key processes for energy, fuel or chemicals production.•Sustainable microbial electrosynthesis and recovery of energy efficient processes is a recent application.•Future perspectives include overcoming limitations for commercialization of BES technology.
In this study, we reported the preparation of Quintinite-3T (Q-3T) and its use as a productive efficient/effective heterogeneous catalyst for the production of biodiesel. Quintinite-3T (Q-3T) has ...been successfully synthesized via the co-precipitation method. Physico-chemical properties of the synthesized catalyst were studied using powder X-Ray diffraction (XRD), High-resolution transmission electron microscopy (HR-TEM), BET analysis, and Thermogravimetric analysis (TGA). Q-3T exhibited promising utility as a heterogeneous catalyst to transesterify Jatropha curcas oil (JCO) and used cooking oil (UCO) to fatty acid methyl ester (FAME). Q-3T catalyst was used with KOH, a co-catalyst to verify its effect on biodiesel production. The effective parameters of the transesterification yield involving reaction time, reaction temperature, and the oil-to-alcohol molar ratio was studied. The maximum yield of 82% for biodiesel was reached at ideal conditions, which include a moderate catalyst concentration (2% (w/w) in the ratio 1.2:0.8 (KOH: Q-3T), at a low temperature and relatively short reaction time of 60° C and 1 h, respectively. Additionally, it is found that the biodiesel’s properties are in good conformity with ASTM D6571 fuel specifications. It is pertinent that the use of Q-3T nanocatalyst as a heterogeneous catalyst for biodiesel production from Jatropha curcas oil and used cooking oil could be beneficial.
•Shared AV mobility services (SAMSs) can significantly increase job accessibility.•Job accessibility benefits from SAMSs higher for workers in lower density areas.•Job accessibility benefits from ...SAMSs slightly higher for low-income workers.•Benefits of SAMS transit feeder commute mode minimal compared to SAMS-only mode.•Job accessibility benefits heavily dependent on per-mile costs of SAMS modes.
The goal of this study is to assess and quantify the potential employment accessibility benefits of shared-use automated vehicle (AV) mobility service (SAMS) modes across a large diverse metropolitan region considering heterogeneity in the working population. To meet this goal, this study proposes employing a welfare-based (i.e. logsum-based) measure of accessibility, obtained via estimating a hierarchical work destination-commute mode choice model. The employment accessibility logsum measure incorporates the spatial distribution of worker residences and employment opportunities, the attributes of the available commute modes, and the characteristics of individual workers. The study further captures heterogeneity of workers using a latent class analysis (LCA) approach to account for different worker clusters valuing different types of employment opportunities differently, in which the socio-demographic characteristics of workers are the LCA model inputs. The accessibility analysis results in Southern California indicate: (i) the accessibility benefit differences across latent classes are modest but young workers and low-income workers do see higher benefits than high- and middle-income workers; (ii) there are substantial spatial differences in accessibility benefits with workers living in lower density areas benefiting more than workers living in high-density areas; (iii) nearly all the accessibility benefits come from the SAMS-only mode as opposed to the SAMS+Transit mode; and (iv) the SAMS cost per mile assumption significantly impacts the magnitude of the overall employment accessibility benefits.
Outfitted with numerous coordination and hydrogen bonding sites, nucleotides represent a class of naturally occurring ligands for coordination with metals leading to both hard and soft materials for ...a wide range of applications. Reported herein, a new multistimuli-responsive metal–organic hydrogel through the spontaneous self-associative complexation of inosine 5′-monophosphate (IMP) with Ag(I) ions in aqueous medium. The strong and optically transparent hydrogels were formed without the aid of any external influences such as heating/cooling cycles or ultrasonication and comprise of an interconnected matrix of nanofilaments constructed from helically stacked, chiral arrays of Ag-IMP dimers. The metallogel exhibits diverse properties including self-healing, stimuli-responsiveness, transparency, and injectibility. The direct gelation specificity to Ag (I) ions is highly phase selective only to water, and the ability of the freeze-dried xerogel to gel water is exploited for the separation of water from various organic solvents. Further, the Ag-IMP hydrogel exhibits efficient antibacterial activity against both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria. Ag nanoparticles could be generated in situ without disrupting the hydrogel network through photoreduction by light. The robustness and multidimensional applicability combined with ease of synthesis make this coordination driven hydrogel a prospective material for environmental and biomedical applications.
Extensively studied Mn-doped semiconductor nanocrystals have invariably exhibited photoluminescence over a narrow energy window of width ≤150 meV in the orange-red region and a surprisingly large ...spectral width (≥180 meV), contrary to its presumed atomic-like origin. Carrying out emission measurements on individual single nanocrystals and supported by ab initio calculations, we show that Mn PL emission, in fact, can (i) vary over a much wider range (∼370 meV) covering the deep green--deep red region and (ii) exhibit widths substantially lower (∼60-75 meV) than reported so far, opening newer application possibilities and requiring a fundamental shift in our perception of the emission from Mn-doped semiconductor nanocrystals.
Background
Lakadong turmeric (LKD) from Meghalaya, India, boasts high curcumin levels, but lacks scientific study. Moreover, Curcumin's poor solubility hinders its clinical use in inflammation and ...wound healing. This study isolated curcumin from LKD, forming a PLGA nanosuspension-based nanogel and explored for its potential anti-inflammatory and cutaneous wound healing activity in Wistar rats.
Methodology
The LKD rhizome was successively extracted by soxhlet using chloroform, hexane, ethyl acetate and methanol and their total phenolic content and antioxidant property was determined. Chloroform extract was loaded in column chromatography and curcumin was isolated, purified and characterized by FTIR, NMR, DSC, MS and HPTLC and its purity was analyzed by HPLC. The isolated curcumin was loaded into PLGA nanosuspensions by nanoprecipitation method followed by conversion to carbopol based Nanogel. The nanogels were characterized physicochemically and the drug permeation was observed. The optimized nanogel was evaluated for its anti-inflammatory and cutaneous wound healing activity by carrageenan-induced paw edema and excision wound model in albino Wistar rats divided in five groups and treated with plain carbopol gel, marketed turmeric cream and Cur NS nanogel (0.6% w/w equivalent curcumin each).
Results
Results depicted that the chloroform extract showed the presence of a considerable amount of phenolics with 50-60% yield of curcumin. HPLC analysis depicted that the LKD curcumin had higher purity when compared to standard curcumin. Homogenous curcumin nanosuspensions were obtained with size 150 ± 50 nm and PDI 0.2 ± 0.1. The Cur-NS-nanogel showed satisfactory physical property, drug loading and stability. Ex vivo permeation studies in rats showed controlled permeation with steady state flux of 21.28 ± 0.23 µg/cm
2
/hr in 24 h. Topical intervention with Cur-NS-nanogel (0.6%) significantly (p < 0.05) decreased the paw volume by 43.97% in the 3rd hour and 72.19% on the 4th hour. Furthermore, the cutaneous wound healing property of Cur-NS-nanogel when compared to negative control rats showed a substantial (p < 0.05) reduction in the percentage wound contraction from 5 to 20
th
days.
Conclusion
LKD showed high curcumin content with significant antioxidant effects. LKD curcumin loaded into stable nanogel depicted safe and controlled skin permeability with promising cutaneous wound healing and anti-inflammatory activity in experimental rats.
tetracationic (TMPyP) and tricationic porphyrin (TriMPyCOOHP) derivatives were synthesized, characterized and investigated for binding with DNA by Isothermal Titration Calorimetry as well as by ...UV–Vis spectroscopy in order to study the effect of structural variation on tumor targeting efficacy of cationically charged porphyrin derivatives. Fluorescence cell imaging studies performed in cancer cell lines corroborated the findings of aforementioned studies. Photocytotoxicity experiments in A549 cell lines revealed relatively higher light dependent cytotoxic effects exerted by TMPyP compared to TriMPyCOOHP. In-vivo experiments in tumor bearing animal model revealed relatively longer retention of 68Ga-TMPyP in tumorous lesion compared to that of 68Ga-TriMPyCOOHP. The study reveals that removal of one of the positive charges of the tetracationic porphyrin derivatives significantly reduces their DNA binding ability and cytotoxicity as well as brings changes in the pharmacokinetic pattern and tumor retention in small animal model.
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•Synthesized a tetracationic (TMPyP) and a tricationic porphyrin (TriMPyCOOHP).•Studied the effect of structural variation of cationic porphyrin on tumor targeting efficacy.•Photo-cytotoxic effect exerted by TMPyP was significantly higher than that exerted by TriMPyCOOHP.•68Ga-TMPyP exhibited longer tumor retention compared to that of 68Ga-TriMPyCOOHP.•Loss of one + ve charge results reduction of DNA binding ability & cytotoxicity of tetracationic porphyrins.
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