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At least 1,027 records · Page 57

Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4{sup +} naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4{sup +} naive T cells.

60 APPLIED LIFE SCIENCES↗

Synthesis and Characterization of the Lithium-Rich Core-Shell Cathodes with Low Irreversible Capacity and Mitigated Voltage Fade

Lithium-rich layered Ni–Mn–Co oxide materials have been intensely studied in the past decade. Mn-rich materials have serious voltage fade issues, and the Ni-rich materials have poor thermal stability and readily oxidize the organic carbonate electrolyte. Core–shell (CS) strategies that use Ni-rich material as the core and Mn-rich materials as the shell can balance the pros and cons of these materials in a hybrid system. The lithium-rich CS materials introduced here show much improved overall electrochemical performance compared to the core-only and shell-only samples. Energy dispersive spectroscopy results show that there was diffusion of transition metals between the core and shell phases after sintering at 900 °C compared to the prepared hydroxide precursors. A Mn-rich shell was still maintained whereas the Co which was only in the shell in the precursor was approximately homogeneous throughout the particles. The CS samples with optimal lithium content showed low irreversible capacity (IRC), as well as high capacity and excellent capacity retention. Sample CS2-3 (the third sample in the 0.67Li 1+x (Ni₀.₆₇Mn₀.₃₃) 1–x O₂·0.33Li 1+y (Ni₀.₄Mn₀.₅Co₀.₁) 1–y O₂ CS2 series) had a reversible capacity of ~218 mAh/g with 12.3% (~30 mAh/g) irreversible capacity (IRC) and 98% capacity retention after 40 cycles to 4.6 V at 30 °C at a rate of ~C/20. Differential capacity versus potential (dQ/dV versus V) analysis confirmed that cells of the CS samples had stable impedance as well as a very stable average voltage. Apparently, the Mn-rich shell can effectively protect the Ni-rich core from reactions with the electrolyte while the Ni-rich core renders a high and stable average voltage.

36 MATERIALS SCIENCE↗

Iridium Surface Oxide Affects the Nafion Interface in Proton-Exchange-Membrane Water Electrolysis

Proton-exchange-membrane water electrolyzer (PEMWE) catalyst layers consist of aggregates of catalyst particles (typically iridium) and ionomer (typically Nafion). Prior work suggests that the oxide form of Ir affects the kinetics of the oxygen-evolution reaction. However, because most catalyst-benchmarking studies are conducted ex situ in liquid electrolytes, it remains unclear how the ionomer is influenced by the catalyst oxide and affects overall cell performance. Using a suite of experimental techniques, we conduct fundamental investigations into model ink (catalyst and ionomer dispersed in solution) and thin-film systems to inform cell-level overpotential analysis as a function of three forms of Ir (metallic Ir m , oxyhydroxide IrOOH, and oxide IrO 2 ). Furthermore, nafion on Ir m has a high degree of phase separation and higher swelling, likely improving the ionic conductivity. Additionally, Nafion binds most strongly to IrOOH, likely yielding reduced kinetic overpotentials. These findings highlight the intricacies of the ionomer/Ir interface and provide insight into all catalyst-layer systems.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Organic-Acid-Assisted Fabrication of Low-Cost Li-Rich Cathode Material (Li[Li1/6Fe1/6Ni1/6Mn1/2]O-2) for Lithium-Ion Battery

A novel Li-rich cathode Li[Li1/6Fe1/6Ni1/6Mn1/2]O-2 (0.4Li(2)MnO(3-)0.6LiFe(1/3)Ni(1/3)Mn(1/3)O(2)) was synthesized by a solgel method, which uses citric acid (SC), tartaric acid (ST), or adipic acid (SA) as a chelating agent. The structural, morphological, and electrochemical properties of the prepared samples were characterized by various methods. X-ray diffraction showed that single-phase materials are formed mainly with typical alpha-NaFeO2 layered structure (R3 m), and the SC sample has the lowest Li/Ni cation disorder. The morphological study indicated homogeneous primary particles in good distribution size (100 nm) with small aggregates. The Fe, Ni, and Mn valences were determined by X-ray absorption near-edge structure analysis. In coin cell tests, the initial reversible discharge capacity of an SA electrode was 289.7 mAh g(-1) at the 0.1C rate in the 1.54.8 V voltage range, while an SC electrode showed a better cycling stability with relatively high capacity retention. At the 2C rate, the SC electrode can deliver a discharge capacity of 150 mAh g(-1) after 50 cycles. Differential capacity vs voltage curves were employed to further investigate the electrochemical reactions and the structural change process during cycling. This low-cost, Fe-based compound prepared by the solgel method has the potential to be used as the high capacity cathode material for Liion batteries.

cathode↗

A scalable membrane electrode assembly architecture for efficient electrochemical conversion of CO2 to formic acid

Abstract The electrochemical reduction of carbon dioxide to formic acid is a promising pathway to improve CO 2 utilization and has potential applications as a hydrogen storage medium. In this work, a zero-gap membrane electrode assembly architecture is developed for the direct electrochemical synthesis of formic acid from carbon dioxide. The key technological advancement is a perforated cation exchange membrane, which, when utilized in a forward bias bipolar membrane configuration, allows formic acid generated at the membrane interface to exit through the anode flow field at concentrations up to 0.25 M. Having no additional interlayer components between the anode and cathode this concept is positioned to leverage currently available materials and stack designs ubiquitous in fuel cell and H 2 electrolysis, enabling a more rapid transition to scale and commercialization. The perforated cation exchange membrane configuration can achieve >75% Faradaic efficiency to formic acid at <2 V and 300 mA/cm 2 in a 25 cm 2 cell. More critically, a 55-hour stability test at 200 mA/cm 2 shows stable Faradaic efficiency and cell voltage. Technoeconomic analysis is utilized to illustrate a path towards achieving cost parity with current formic acid production methods.

08 HYDROGEN↗

Expanded encyclopaedias of DNA elements in the human and mouse genomes

The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.

59 BASIC BIOLOGICAL SCIENCES↗

Evolution of neuronal cell classes and types in the vertebrate retina

The basic plan of the retina is conserved across vertebrates, yet species differ profoundly in their visual needs1. Retinal cell types may have evolved to accommodate these varied needs, but this has not been systematically studied. Here we generated and integrated single-cell transcriptomic atlases of the retina from 17 species: humans, two non-human primates, four rodents, three ungulates, opossum, ferret, tree shrew, a bird, a reptile, a teleost fish and a lamprey. We found high molecular conservation of the six retinal cell classes (photoreceptors, horizontal cells, bipolar cells, amacrine cells, retinal ganglion cells (RGCs) and Müller glia), with transcriptomic variation across species related to evolutionary distance. Major subclasses were also conserved, whereas variation among cell types within classes or subclasses was more pronounced. However, an integrative analysis revealed that numerous cell types are shared across species, based on conserved gene expression programmes that are likely to trace back to an early ancestral vertebrate. The degree of variation among cell types increased from the outer retina (photoreceptors) to the inner retina (RGCs), suggesting that evolution acts preferentially to shape the retinal output. Finally, we identified rodent orthologues of midget RGCs, which comprise more than 80% of RGCs in the human retina, subserve high-acuity vision, and were previously believed to be restricted to primates. By contrast, the mouse orthologues have large receptive fields and comprise around 2% of mouse RGCs. Projections of both primate and mouse orthologous types are overrepresented in the thalamus, which supplies the primary visual cortex. We suggest that midget RGCs are not primate innovations, but are descendants of evolutionarily ancient types that decreased in size and increased in number as primates evolved, thereby facilitating high visual acuity and increased cortical processing of visual information.

59 BASIC BIOLOGICAL SCIENCES↗

Evaluating aqueous flow battery electrolytes: a coordinated approach

Here, we outline some basic pitfalls in the electrochemical investigation of aqueous metal complexes and advocate for the use of bulk electrolysis in redox flow cells for electrolyte analysis. We demonstrate the methods of operation and performance of a lab scale redox flow battery (RFB), which is assembled from unmodified, commercially available material and cycled with a vanadium electrolyte in order to provide a comparative baseline of expected performance. Common misconceptions about the thermodynamic window for water splitting are addressed and further express the need to develop next-generation aqueous redox flow battery electrolytes. Although non-aqueous electrolytes are a popular approach, they suffer from distinct challenges that limit energy and power density in comparison with aqueous electrolytes. Expanding the scope of aqueous electrolytes to include metal–chelate complexes allows electrolytes to be as tailorable as organic species, while maintaining robust metal-based redox processes. A flow battery assembly and operation guide is provided to help facilitate the use of flow battery testing in the evaluation of next-generation electrolytes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Saturation mechanisms of backward stimulated Raman scattering in a one-dimensional geometry

In this paper, we investigate the saturation mechanisms of backward stimulated Raman scattering (BSRS) induced by nonlinear kinetic effects. In particular, we stress the importance of accounting for both the nonlinear frequency shift of the electron plasma wave and the growth of sidebands, in order to understand what stops the coherent growth of Raman scattering. Using a Bernstein-Greene-Kruskal approach, we provide an estimate for the maximum amplitude reached by a BSRS-driven plasma wave after the phase of monotonic growth. This estimate is in very good agreement with the results from kinetic simulations of stimulated Raman scattering using both a Vlasov and a Particle in Cell code. Our analysis, which may be generalized to a multidimensional geometry, should provide a means to estimate the limits of backward Raman amplification or the effectiveness of strategies that aim at strongly reducing Raman reflectivity in a fusion plasma.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Purification of the output modes of overmoded relativistic backward wave oscillators

Successful suppression of mode competition in the beam-wave interaction process of overmoded relativistic backward wave oscillators (RBWOs) cannot ensure the output modes purity. Optimizing the magnitude and the phase of the mode conversion coefficients in the devices is significant for purifying the output modes. A universal method of purifying the TM{sub 01} and TM{sub 02} mixed modes output by overmoded RBWOs without decreasing the total output power is presented in this paper. With this method, we purify the TM{sub 01} and TM{sub 02} mixed modes generated in an X-band overmoded RBWO (D/λ ≈ 2.6) operated at the constant diode voltage of 730 kV. Dependence of modes purification effect on the variation of diode voltage is also analyzed in particle-in-cell simulation. Our analysis indicates that when the diode voltage is in the range of (730 ± 60) kV, the percentage of output power carried by TM{sub 01} mode will be higher than 95%.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

The structure of carbon monoxide adsorbed on the NaCl(100) surface—A combined LEED and DFT-D/vdW-DF study

The structure of the first layer CO adsorbed on NaCl(100) is investigated experimentally by means of quantitative low-energy electron diffraction at 25 K, and theoretically by means of density functional theory. Consistent with earlier helium atom diffraction results, the monolayer structure has p(2×1) symmetry with a glide-plane along the longer axis of the unit cell. The structure analysis confirms the binding of CO via the carbon end to the NaCl(100) surface. The vertical distance of carbon above Na{sup +} is 2.58 ± 0.08 Å, in good agreement with geometry optimizations based on dispersion-corrected density functional theory, and 0.15 Å lower than predicted in calculations based on the nonlocal van der Waals density functional.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Efficient passivation of n-type and p-type silicon surface defects by hydrogen sulfide gas reaction

An efficient surface defect passivation is observed by reacting clean Si in a dilute hydrogen sulfide-argon gas mixture (< 5% H2S in Ar) for both n-type and p-type Si wafers with planar and textured surfaces. Surface recombination velocities of 1.5 and 8 cm/s are achieved on n-type and p-type Si wafers, respectively, at an optimum reaction temperature of 550oC that are comparable to the best surface passivation quality used in high efficiency Si solar cells. Surface chemical analysis using x-ray photoelectron spectroscopy shows that sulfur is primarily bonded in a sulfide environment, and synchrotron-based soft x-ray emission spectroscopy of the adsorbed sulfur atoms suggests the formation of S-Si bonds. Furthermore, the sulfur surface passivation layer is unstable in air, attributed to surface oxide formation and a simultaneous decrease of sulfide bonds. However, the passivation can be stabilized by a low-temperature (300oC) deposited amorphous silicon nitride (a-Si:NX:H) capping layer.

14 SOLAR ENERGY↗

Disruption of p -coumaroyl-CoA:monolignol transferases in rice drastically alters lignin composition

Grasses are abundant feedstocks that can supply lignocellulosic biomass for production of cell-wall-derived chemicals. In grass cell walls, lignin is acylated with p-coumarate. These p-coumarate decorations arise from the incorporation of monolignol p-coumarate conjugates during lignification. A previous biochemical study identified a rice (Oryza sativa) BAHD acyltransferase (AT) with p-coumaroyl-CoA:monolignol transferase (PMT) activity in vitro. In this study, we determined that that enzyme, which we name OsPMT1 (also known as OsAT4), and the closely related OsPMT2 (OsAT3) harbor similar catalytic activity toward monolignols. We generated rice mutants deficient in either or both OsPMT1 and OsPMT2 by CRISPR/Cas9-mediated mutagenesis and subjected the mutants’ cell walls to analysis using chemical and nuclear magnetic resonance methods. Our results demonstrated that OsPMT1 and OsPMT2 both function in lignin p-coumaroylation in the major vegetative tissues of rice. Notably, lignin-bound p-coumarate units were undetectable in the ospmt1 ospmt2-2 double-knockout mutant. Further, in-depth structural analysis of purified lignins from the ospmt1 ospmt2-2 mutant compared with control lignins from wild-type rice revealed stark changes in polymer structures, including alterations in syringyl/guaiacyl aromatic unit ratios and inter-monomeric linkage patterns, and increased molecular weights. Furthermore, our results provide insights into lignin polymerization in grasses that will be useful for the optimization of bioengineering approaches for the effective use of biomass in biorefineries.

59 BASIC BIOLOGICAL SCIENCES↗

Dissecting subcycle interference in photoelectron holography

Multipath holographic interference in strong-field quantum tunnel ionization is key to revealing subangstrom attosecond dynamics for molecular movies. This critical subcycle motion is often obscured by longer timescale effects such as ring-shaped patterns that appear in above-threshold ionization (ATI). In the present work, we overcome this problem by combining two techniques in theory and experimental analysis: unit-cell averaging and time-filtering data and simulations. Together these suppress ATI rings and enable an unprecedented highly detailed quantitative match between strong-field ionization experiments in argon and the Coulomb-quantum orbit strong-field approximation (CQSFA) theory. Velocity map images reveal fine modulations on the holographic spiderlike interference fringes that form near the polarization axis. CQSFA theory traces this to the interference of three types of electron pathways. The level of agreement between experiment and theory allows sensitive determination of quantum phase differences and symmetries, providing an important tool for quantitative dynamical imaging in quantum systems.

74 ATOMIC AND MOLECULAR PHYSICS↗

Novel CHI3L1 ‐Associated Angiogenic Phenotypes Define Glioma Microenvironments: Insights From Multi‐Omics Integration

ABSTRACT The CHI3L1 signaling pathway significantly influences glioma angiogenesis, but its role in the tumor microenvironment (TME) remains elusive. We propose a novelCHI3L1‐associated vascular phenotype classification for glioma through integrative analyses of multiple datasets with bulk and single‐cell transcriptome, genomics, digital pathology, and clinical data. We investigated the biological characteristics, genomic alterations, therapeutic vulnerabilities, and immune profiles within these phenotypes through a comprehensive multi‐omics approach. We constructed the vascular‐related risk (VR) score based onCHI3L1‐associated vascular signatures (CAVS) identified by machine learning algorithms. Utilizing unsupervised consensus clustering, gliomas were stratified into three distinct vascular phenotypes: Cluster A, marked by high vascularization and stromal activation with a relatively low levels of tumor‐infiltrating lymphocytes (TILs); Cluster B, characterized by moderate vascularization and stromal activity, coupled with a high density of TILs; and Cluster C, defined by low vascularization and sparse immune cell infiltration. We observed that the CAVS effectively indicated glioma‐associated angiogenesis and immune suppression by single‐cell RNA‐seq analysis. Moreover, the high‐VR‐score group exhibited enhanced angiogenic activity, reduced immune response, resistance to immunotherapy, and poorer clinical outcomes. The VR score independently predicted glioma prognosis and, combined with a nomogram, provided a robust clinical decision‐making tool. Potential drug prediction based on transcription factors for high‐risk patients was also performed. Our study reveals thatCHI3L1‐associated vascular phenotypes shape distinct immune landscapes in gliomas, offering insights for optimizing therapeutic strategies to improve patient outcomes.

Oncology↗

Bioenergy sorghum’s deep roots: A key to sustainable biomass production on annual cropland

Abstract Bioenergy sorghum has high biomass yield potential, drought resilience, good nitrogen use efficiency, and a root system that contributes to the accumulation of soil organic carbon. In this study, field grown bioenergy sorghum root systems were analyzed during the growing season to characterize their depth, biomass, morphology, anatomy, and gene expression profiles. Bioenergy sorghum roots grew continuously during a 155‐day growing season producing ~175 nodal roots, accumulating ~7 Mg of dry biomass per hectare, and reaching >2 m deep in the soil profile. Nodal roots within 20 cm of the stem were 1–5 mm in diameter, whereas roots deeper in soil profiles were enriched in lateral roots with small diameters (~30–500 µm) enabling growth through soil macropores. In older field‐grown plants, roots with intact endodermal, vascular and inner root tissues were surrounded by degraded or aerenchyma‐filled epidermal and cortical cell layers. Transcriptome analysis of nodal, surface, and deep roots identified >2,500 differentially expressed genes involved in root growth, transport, adaptation, defense, and AMF–root interaction. Deep roots (180–240 cm) differentially expressed genes that regulate lateral root growth. Surface roots (0–20 cm) located mid‐row differentially expressed genes involved in nitrate transport, whereas ammonium transport genes were expressed in surface and deep roots and genes involved in phosphate transport were expressed in nodal, surface, and deep roots. Overall, bioenergy sorghum's long growing season enables root systems to grow deeper and accumulate more biomass than annual grain crops such as maize, attributes that could help restore annual cropland soil organic carbon levels and improve soil productivity. Deep roots active in nutrient transport are positioned to take‐up fertilizer leached deep into soil profiles mitigating potential nutrient run‐off. Bioenergy sorghum's large and deep root system is a key to sustainable production of biofuels, biopower, and bioproducts on annual cropland.

59 BASIC BIOLOGICAL SCIENCES↗

Estimation of elastic properties of an additively manufactured lattice using resonant ultrasound spectroscopy

Development of improved approaches in the characterization of additively manufactured structures continues to be a topic of interest for the advanced manufacturing community. This article will investigate an approach using resonant ultrasound spectroscopy (RUS) to determine the effective elastic constants of an orthotropic lattice structure. The evaluation is performed on a cube shaped 316 L stainless steel test specimen, constructed using selective laser melting techniques. The approach uses RUS techniques in conjunction with the assumption that in the frequency regime of interest, the wavelength of the diagnostic ultrasound is greater than the discrete structural features of the unit cell of the lattice; thus, the AM structure can be treated as an anisotropic continuum with effective material properties and symmetry inherited from the unit cell. The RUS analysis estimates the nine elastic coefficients associated with orthotropic sample symmetry, which, in turn, are used to determine the elastic moduli and Poisson ratios. Current results show good agreement between experiments and modeled data. Comparisons to published results are also in good agreement, indicating the potential applicability of this characterization technique for estimating the linear elastic properties of innovative additive manufactured metal lattice structures.

36 MATERIALS SCIENCE↗

Increased mortality in mice following immunoprophylaxis therapy with high dosage of nicotinamide in Burkholderia persistent infections

Bacterial persistence, known as non-inherited antibacterial resistance, is a contributing factor to the establishment of long-lasting chronic bacterial infections. In this study, we examined the ability of nicotinamide (NA) to potentiate different classes of antibiotics against Burkholderia thailandensis persister cells. Here we demonstrate that addition of NA in in vitro models of B. thailandensis infection resulted in a significant depletion of the persister population in response to various classes of antibiotics. We applied microfluidic bioreactors with a continuous media flow to study the effect of supplementation with a NA gradient on the recovery of B. thailandensis persister populations. A co-culture of human neutrophils pre-activated with 50 µM NA and B. thailandensis resulted in the most efficient reduction in the persister population. Applying single cell RNA FISH analysis and quantitative PCR, we found that NA inhibited gene expression of the stringent response regulator relA , implicated in the regulation of the persister metabolic state. In conclusion, we also demonstrate that a therapeutic dose of NA (250mg/kg), previously applied as immunoprophylaxis against antibiotic-resistant bacterial species, produced adverse effects in an in vivo murine infection model of the highly pathogenic Burkholderia pseudomallei , indicating that therapeutic dose and metabolite effects have to be carefully evaluated and tailored for every case of potential clinical application.

60 APPLIED LIFE SCIENCES↗