Changes In Content Research Articles

Impact of Cereal–Legume Intercropping on Changes in Soil Nutrients Contents under Semi–Arid Conditions

Cereal–legume intercropping systems are not well studied under the semi–arid conditions of Southern Tunisia. Therefore, the present study aimed to investigate the effect of intercropping durum wheat (Triticum turgidum ssp. durum L.) with chickpea (Cicer arietinum L.) on crop grain yield and soil physicochemical proprieties such as carbon (C) and nitrogen (N) availability, microbial biomass nutrients (C and N) and plant nutrient content (N) in comparison to their monocultures. Field experiments were conducted during the 2020–2021 (EXP–A) and 2021–2022 (EXP–B) seasons in Medenine, Tunisia. The results revealed a significant augmentation (p < 0.05) in the total nitrogen proportions (Ntot) within the soil of intercropped durum wheat (DuWh–IR) compared to its monoculture (DuWh–MC). The observed variations amounted to 32% and 29% during the two growing seasons, identified as EXP–A and EXP–B. Additionally, the soil of intercropped durum wheat (DuWh–IR) significantly (p < 0.05) accumulated more total carbon (Ctot) than the monocrop (DuWh–MC) for both experiments, showing an increase of 27% in EXP–A and 24% in EXP–B. Simultaneously, the N− uptake of durum wheat significantly increased under the effect of intercropping, showing a rise of 26% in the EXP–A season and 21% in the EXP–B season. Similarly, the yield of durum wheat crops was comparatively greater in the intercropped plots as opposed to the monoculture crops, with variances of 23% in EXP–A and 20% in EXP–B. Intercropping cereals and legumes has the potential to enhance the soil fertility and crop production in the semi–arid regions of Southern Tunisia and contribute to environmental sustainability by reducing reliance on nitrogen fertilizers.

Relative Water Content, Chlorophyll Index, and Photosynthetic Pigments on Lotus corniculatus L. in Response to Water Deficit.

This study aimed to evaluate different L. corniculatus L. ecotypes under water-deficit conditions to identify changes in relative water content and photosynthetic pigments as indicators of physiological responses during different years' seasons. The experiment was conducted in a randomized block design with three replicates. Ten treatments were performed as a factorial of 2 × 5, where the first variation factor was the soil water content-no water deficit (NDW) with 100% field capacity (FC), and water deficit (DW) corresponding to 85.4% of the FC-and the second variation factor comprised four ecotypes and one variety of L. corniculatus. A significant effect was identified on the concentration of photosynthetic pigments, mainly total chlorophyll, with chlorophyll a in the 255301 ecotype with records of 187.8, 167.5, and 194.6 mg g-1 FW in WD, corresponding to an increase of 86.0%, 172.6%, and 16.6%, respectively, in relation the lower values obtained in the ecotype 202700 under NWD. In carotenoids, higher concentrations were observed in the 255301 and 202700 ecotypes and the Estanzuela Ganador variety under WD in most seasonal periods, except summer; a similar response was found in the 202700 ecotype and the Estanzuela Ganador variety during the winter season, also in WD. The results showed that the first two principal components accounted for 71.8% of the total variation, with PC1 representing chlorophyll a, chlorophyll b, and total chlorophyll, and PC2 representing carotenoids, temperature, relative chlorophyll index, and relative water content. The observations were grouped based on soil moisture content, with the optimal moisture group exhibiting higher chlorophyll and carotenoid concentrations. The findings suggest that soil moisture content significantly affects the performance of L. corniculatus ecotypes, and the plant shows seasonal variations in response to water-deficit conditions. This research contributes to understanding the physiological responses of L. corniculatus and its potential as a water-efficient forage crop for promoting sustainable agriculture and enhancing food security.

Ocean Heat Content Increase of the Maritime Continent Since the 1990s

AbstractThe Maritime Continent (MC), a critical region for inter‐basin climate interaction, harbors the world's highest marine biodiversity. Ocean warming in the MC, although with notable impacts on regional climate and marine ecosystems, remains poorly constrained by observations. By applying a volume‐correction algorithm to existing gridded observational data sets, this study provides an estimate for the ocean heat content (OHC) change of the MC. The results suggest a substantial OHC increase of 2.65 ± 0.46 Zettajoules during 1990–2015 (1.08 ± 0.17 W m−2) and limited changes before and after. This increase primarily arose from the enhanced Pacific Walker circulation, which drove a convergence of upper‐layer warm water toward the MC. A potential heat storage “hotspot” with enhanced warming below 500 m emerges within the Sulu Sea, which is supported by analysis of profile data collected in boreal winter but not in other seasons.

Evaluating physiochemical characteristics of tragacanth gum-gelatin network hydrogels designed through graft copolymerization technique

The present work deals with the evaluation of the physiochemical and biomedical properties of hydrogels derived from copolymerization of tragacanth gum (TG) and gelatin for use in drug delivery (DD) applications. Copolymers were characterized by field emission-scanning electron micrographs (FE-SEM), electron dispersion X-ray analysis (EDAX), Fourier transform infrared spectroscopy (FTIR), 13C-nuclear magnetic resonance (NMR), thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. FE-SEM revealed heterogeneous morphology and XRD analysis demonstrated an amorphous nature with short range pattern of polymer chains within the copolymers. The release of the drug ofloxacin occurred through a non-Fickian diffusion mechanism and the release profile was best described by the Korsmeyer-Peppas kinetic model. The hydrogels exhibited blood compatibility and demonstrated a thrombogenicity value of 75.63 ± 1.98 % during polymer-blood interactions. Polymers revealed mucoadhesive character during polymer-mucous membrane interactions and required 119 ± 8.54 mN detachment forces to detach from the biological membrane. The copolymers illustrated the antioxidant properties as evidenced by 2, 2′-diphenylpicrylhydrazyl (DPPH) assay which demonstrated a 65.71 ± 3.68 % free radical inhibition. Swelling properties analysis demonstrated that by change in monomer and cross linker content during the reaction increased the crosslinking of the network. These results suggest that the pore size of network hydrogels could be controlled as per the requirement of DD systems. The copolymers were prepared at optimized reaction conditions using 14.54 × 10−1 molL−1 of acrylic acid monomer and 25.0 × 10−3 molL−1 of crosslinker NNMBA. The optimized hydrogels exhibited a crosslink density of 2.227 × 10−4 molcm−3 and a mesh size of 7.966 nm. Additionally, the molecular weight between two neighboring crosslinks in the hydrogels was determined to be 5332.209 gmol−1.The results indicated that the combination of protein-polysaccharide has led to the development of hydrogels suitable for potential applications in sustained drug delivery.

Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their Secretome.

Extracellular vesicles (EVs) are secreted from many tumors, including glioblastoma multiforme (GBM), the most common and lethal brain tumor in adults, which shows high resistance to current therapies and poor patient prognosis. Given the high relevance of the information provided by cancer cell secretome, we performed a proteomic analysis of microvesicles (MVs) and exosomes (EXOs) released from GBM-derived stem cells (GSCs). The latter, obtained from the brain of GBM patients, expressed P2X7 receptors (P2X7Rs), which positively correlate with GBM growth and invasiveness. P2X7R stimulation of GSCs caused significant changes in the EV content, mostly ex novo inducing or upregulating the expression of proteins related to cytoskeleton reorganization, cell motility/spreading, energy supply, protection against oxidative stress, chromatin remodeling, and transcriptional regulation. Most of the induced/upregulated proteins have already been identified as GBM diagnostic/prognostic factors, while others have only been reported in peripheral tumors. Our findings indicate that P2X7R stimulation enhances the transport and, therefore, possible intercellular exchange of GBM aggressiveness-increasing proteins by GSC-derived EVs. Thus, P2X7Rs could be considered a new druggable target of human GBM, although these data need to be confirmed in larger experimental sets.

Tumescenamide C, a cyclic lipodepsipeptide from Streptomyces sp. KUSC_F05, exerts antimicrobial activity against the scab-forming actinomycete Streptomyces scabiei.

The antimicrobial activity of tumescenamide C against the scab-forming S. scabiei NBRC13768 was confirmed with a potent IC50 value (1.5 μg/mL). Three tumescenamide C-resistant S. scabiei strains were generated to compare their gene variants. All three resistant strains contained nonsynonymous variants in genes related to cellobiose/cellotriose transport system components; cebF1, cebF2, and cebG2, which are responsible for the production of the phytotoxin thaxtomin A. Decrease in thaxtomin A production and the virulence of the three resistant strains were revealed by the LC/MS analysis and necrosis assay, respectively. Although the nonsynonymous variants were insufficient for identifying the molecular target of tumescenamide C, the cell wall component wall teichoic acid (WTA) was observed to bind significantly to tumescenamide C. Moreover, changes in the WTA contents were detected in the tumescenamide C-resistant strains. These results imply that tumescenamide C targets the cell wall system to exert antimicrobial effects on S. scabiei.

Meta-Crafting: Improved Detection of Out-of-Distributed Texts via Crafting Metadata Space (Student Abstract)

Detecting out-of-distribution (OOD) samples is crucial for robust NLP models. Recent works observe two OOD types: background shifts (style change) and semantic shifts (content change), but existing detection methods vary in effectiveness for each type. To this end, we propose Meta-Crafting, a unified OOD detection method by constructing a new discriminative feature space utilizing 7 model-driven metadata chosen empirically that well detects both types of shifts. Our experimental results demonstrate state-of-the-art robustness to both shifts and significantly improved detection on stress datasets.

Plasticity changes in iron homeostasis in hibernating Daurian ground squirrels (Spermophilus dauricus) may counteract chronically inactive skeletal muscle atrophy.

Disuse-induced muscular atrophy is frequently accompanied by iron overload. Hibernating animals are a natural animal model for resistance to disuse muscle atrophy. In this paper, we explored changes in skeletal muscle iron content of Daurian ground squirrels (Spermophilus dauricus) during different periods of hibernation as well as the regulatory mechanisms involved. The results revealed that compared with the summer active group (SA), iron content in the soleus muscle (SOL) decreased (- 65%) in the torpor group (TOR), but returned to normal levels in the inter-bout arousal (IBA); splenic iron content increased in the TOR group (vs. SA, + 67%), decreased in the IBA group (vs. TOR, - 37%). Expression of serum hepcidin decreased in the TOR group (vs. SA, - 22%) and returned to normal levels in the IBA groups; serum ferritin increased in the TOR group (vs. SA, + 31%), then recovered in the IBA groups. Soleus muscle transferrin receptor 1 (TfR1) expression increased in the TOR group (vs. SA, + 83%), decreased in the IBA group (vs. TOR, - 30%); ferroportin 1 increased in the IBA group (vs. SA, + 55%); ferritin increased in the IBA group (vs. SA, + 42%). No significant differences in extensor digitorum longus in iron content or iron metabolism-related protein expression were observed among the groups. Significantly, all increased or decreased indicators in this study returned to normal levels after the post-hibernation group, showing remarkable plasticity. In summary, avoiding iron overload may be a potential mechanism for hibernating Daurian ground squirrels to avoid disuse induced muscular atrophy. In addition, the different skeletal muscle types exhibited unique strategies for regulating iron homeostasis.

The inhibition of MARCO by PolyG alleviates pulmonary fibrosis via regulating mitochondrial function in a silicotic rat model.

Silicon dioxide (SiO2)-induced pulmonary fibrosis is potentially associated with the impairment of mitochondrial function. Previous research found that inhibition of macrophage receptor with collagenous structure (MARCO) could alleviate particle-induced lung injury by regulating phagocytosis and mitigating mitochondrial damage. The present study aims to explore the underlying anti-fibrosis mechanism of polyguanylic acid (PolyG, MARCO inhibitor) in a silicotic rat model. Hematoxylin and eosin and Masson staining were performed to visualize lung tissue pathological changes. Confocal microscopy, transmission electron microscope, western blot analysis, quantitative real-time PCR (qPCR), andadenosine triphosphate (ATP) content assay were performed to evaluate collagen content, mitochondrial function, and morphology changes in SiO2-induced rat pulmonary fibrosis. The results suggested that SiO2 exposure contributed to reactive oxygen species aggregation and the reduction of respiratory complexes and ATP synthesis. PolyG treatment could effectively reduce MARCO expression and ameliorate lung injury and fibrosis by rectifying the imbalance of mitochondrial respiration and energy synthesis. Furthermore, PolyG could maintain mitochondrial homeostasis by promoting peroxisome proliferator-activated receptor-coactivator 1 α (PGC1α)-mediated mitochondrial biogenesis and regulating fusion and fission. Together, PolyG could ameliorate SiO2-induced pulmonary fibrosis via inhibiting MARCO to protect mitochondrial function.

Study on the characterization and thermal conversion behavior of sequential extraction products from medium temperature coal pitch

To achieve the high value-added clean utilization of medium temperature coal pitch (MTP), five fractions were separated from MTP by the sequential extraction method using n-heptane, n-butanol, toluene, tetrahydrofuran and quinoline as solvents. Briefly, the extracts were analysed using proximate analysis, elemental analysis, fourier infrared spectrum (FTIR), ultraviolet visible spectrum (UV–vis), fluorescence spectrum, and thermogravimetric analysis (TGA) to investigate their structural parameters, aromatic condensation degree and pyrolysis properties. Meanwhile, Raman spectrum, X-ray diffraction (XRD), and polarizing microscope were used to quantitatively analyze the microstructures of thermal conversion products of the extracts. This allowed for investigation of the thermal conversion mechanism and determination of the thermal conversion behavior. In fact, the chain index (CH3/CH2), aromatic index (Iar), aromatic condensation degree and thermal stability of the extracts increase gradually with deeper extraction. Extracts with high aromatic condensation degree are more favorable for the formation of mesocarbon microbeads (MCMBs). However, overly aromatic condensation degree will lead to excessive coalescence of MCMBs. The ideal carbon microcrystalline content increases with higher temperatures during the thermal conversion of the same fraction. But the change of amorphous carbon content has no obvious regularity. The results of this work will provide theoretical and experimental support for the selection of precursors for carbon/graphite materials.

Foliar application of selenium promotes starch content accumulation and quality enhancement in foxtail millet grains

ContextThe northern regions of China are the core production areas for foxtail millet. However, the lack of selenium in the soil constrains local agricultural development. Foliar application of selenium is a significant method to improve selenium levels, yet few studies have systematically analyzed the effects of selenium on the quality of millet, especially its starch content. ObjectiveThis study aims to assess the effects of selenium foliar spray on the starch composition and overall content within millet grains, specifically by elucidating the mechanisms through examining changes in chlorophyll content in the flag leaves during the grain-filling stage and the activity of enzymes related to starch synthesis in the grains. Additionally, this research seeks to determine the optimal rate of selenium application that would maximize the quantity and quality of starch in millet grains. MethodsA two-year field experiment on foxtail millet was conducted with five selenium treatments (Se rates of 0, 20, 40, 60, and 100 g Se/ha, defined as T0, T1, T2, T3, T4 in this study, respectively). Grain starch content, activities of starch synthesis-related enzymes, flag leaves chlorophyll content, and antioxidant status of the flag leaves were measured at seven time points during grain filling. ResultsThe starch content in foxtail millet grains increased quadratically with the application of selenium, reaching a maximum under the T3 treatment, which enhanced the content by 15.27 % and 11.97 % over two years, respectively. The addition of selenium at low concentrations (T1-T3 treatments) not only enhanced the activities of the three starch synthesis-related enzymes, AGPase, SuSy, and SSS, but also delayed the senescence of the flag leaves, thereby promoting grain starch synthesis. In contrast, excessive selenium application (T4 treatment) expedited the aging of the flag leaves, grain starch synthesis was inhibited compared to the T3 treatment. Moreover, foliar application of selenium led to an increase in the SSS activity in the grains, which in turn reduced the content of straight-chain starch. Under the T3 treatment, the grain straight-chain starch content decreased by 22.30 % and 28.35 % over two years, respectively. ConclusionsFoliar application of selenium enhanced the activities of enzymes related to grain starch synthesis and had a dual effect on the senescence process of flag leaves, regulating the content and composition of starch in foxtail millet grains. The spraying concentration of 60 g Se/ha was most favorable for the accumulation and quality improvement of grain starch. ImplicationsThe results of this study will aid in enhancing the value-added potential of foxtail millet starch products through precise fertilization, improving the yield and quality of foxtail millet in northern China.

Incorporation of spray‐dried encapsulated bioactive peptides from coconut (Cocos nucifera L.) meal by‐product in bread formulation

AbstractThis study aimed to stabilize and mask the bitterness of peptides obtained from the enzymatic hydrolysis of coconut‐meal protein with maltodextrin (MD) and maltodextrin‐pectin (MD‐P) as carriers via spray‐drying. Essential (~35%), hydrophobic (~32%), antioxidant (~15%), and bitter (~45%) amino acids comprised a significant fraction of the peptide composition (with a degree of hydrolysis of 33%). The results indicated that the peptide's production efficiency, physical and functional properties, and hygroscopicity improved after spray‐drying. Morphological features of free peptides (fragile and porous structures), spray‐dried with MD (wrinkled with indented structures), and MD‐P combination (relatively spherical particles with smooth surfaces) were influenced by the process type and feed composition. Adding free and microencapsulated peptides to the bread formula (2% W/W) caused changes in moisture content (35%–43%), water activity (0.89–0.94), textural properties (1–1.6 N), specific volume (5.5–6 cm3/g), porosity (18%–27%), and color indices of the fortified product. MD‐P encapsulated peptides in bread fortification resulted in thermal stability and increased antioxidant activity (DPPH and ABTS+ radical scavenging: 4.5%–39.4% and 31.6%–46.8%, respectively). MD‐P (as a carrier) could maintain sensory characteristics and mask the bitterness of peptides in the fortified bread. The results of this research can be used to produce functional food and diet formulations.

Development and validation of VaxConcerns: A taxonomy of vaccine concerns and misinformation with Crowdsource-Viability

We present VaxConcerns, a taxonomy for vaccine concerns and misinformation. VaxConcerns is an easy-to-teach taxonomy of concerns and misinformation commonly found among online anti-vaccination media and is evaluated to produce high-quality data annotations among crowdsource workers, opening the potential adoption of the framework far beyond just academic or medical communities. The taxonomy shows high agreement among experts and outperforms existing taxonomies for vaccine concerns and misinformation when presented to non-expert users. Our proof-of-concept study on the changes in anti-vaccination content during the COVID-19 pandemic indicate impactful future use cases, such as longitudinal studies of the shift in vaccine concerns over time.

Improving introductory economics course content and delivery improves outcomes for women

The presentation of economics in introductory courses has been highlighted as potentially exacerbating the underrepresentation of women in economics. The authors study the impact of a gender-neutral change in content and instruction in introductory economics courses intended to increase student engagement. By implementing meaningful applied problems and structured group work, their intervention focuses on the students’ perceptions of “what” economics is and “how” economics is used. Using institutional data from 8,727 students over nine semesters, they find that the intervention improved women’s grades relative to men’s in both Introductory Microeconomics and Macroeconomics and eliminated underperformance by women in Introductory Macroeconomics relative to men at baseline. These effects are evidence that course content and delivery impact the experiences and outcomes of female students in economics education.

Integrated analysis of transcriptomic and physiological responses to cold stress in Macrobrachium rosenbergii

The giant freshwater prawn (GFP), Macrobrachium rosenbergii, stands out as a vital species in freshwater shrimp aquaculture. However, its susceptibility to cold conditions has increased the cost of aquaculture and limited the growth of GFP cultivation. To furnish insights at the molecular level to enhance GFP's cold tolerance, transcriptome sequencing and physiological analysis of the hepatopancreas were performed in our study. Initially, we identified 4909 differentially expressed genes (DEGs) between experimental (15 °C, 24 h) and control groups (25 °C, 24 h). These DEGs were significantly enriched in the proteasome, spliceosome, lysosome, peroxisome, and lipid metabolism-related pathways including glycerolipid metabolism, sphingolipid metabolism, linoleic acid metabolism as well as steroid hormone biosynthesis. Histological examination following various stress durations revealed a notable increase in hepatocyte vacuoles after 6 h of cold stress. Hepatocyte structure deterioration occurred in the later phase (48 h), coinciding with a significant increase in cell apoptosis. Subsequent analyses demonstrated an initial increase followed by a decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) content, while malonaldehyde (MDA) content rose with stress duration. Furthermore, a significant increase in triglyceride content and no significant change in cholesterol content was observed. RT-qPCR results unveiled significant down-regulated expression of FAS, TAGL, ACOX1, ACS and significant up-regulated expression of GPAT and DEGS. These findings suggest that oxidative stress and impaired lipid metabolism underlie the poor cold tolerance of GFP.

The use of geotextiles in agricultural soils and their effects on soil properties and nutrients availability. Are wastes plastics likely to become useful materials in agriculture?

Experiments were conducted in agricultural soils of central and northern Greece to simulate agricultural practices and to study the effect of geotextile particles on the physical and chemical properties of the soils. Geotextile was added to soil samples in different shapes, dimensions, and proportions (1, 2, and 4% v/v), which remained for different periods (10, 25, 50, 150 days). The physicochemical properties and their changes after adding the geotextile were determined in soil samples. Furthermore, the levels of nutrients in the soils and their changes were evaluated concerning the levels of added plastic and the time they remained in the soil. Once the plastic dimensions were sufficiently large (>5 mm), the changes in the organic matter content and the available trace elements concentration were most pronounced. Plastic residence time appears to be crucial, as the greatest changes in both exchangeable potassium and assimilable phosphorus were observed in the soil samples when the plastic was introduced at the microplastics dimensions (<5 mm), in its maximum amount (4% v/v), and remained within the soil over the longest time (150 days). Knowledge of the chemical composition along with the chemical behavior of plastics used in agricultural practices is particularly important, as it can lead to real benefits to the agricultural economy, being able to regulate the uptake and availability of nutrients already present bound in soils, and reducing the need for continuous need for fertilizer addition, in a circular economy approach.

Abstract 5617: Combined inhibition of ATR and ATM with tuvusertib and lartesertib (M4076) impacts the tumor microenvironment

Abstract Ataxia telangiectasia and Rad3-related protein (ATR) and ataxia telangiectasia mutated (ATM) are two of the main kinases of the DNA damage response (DDR). Recent work has demonstrated that the addition of ATM inhibitors enhances the cytotoxicity and in vivo anti-tumor efficacy of ATR inhibitors by abrogating the ATR inhibitor mediated G1 cell cycle arrest and enhancing chromosomal damage.1 Prior to causing cell death, damaged chromosome fragments can end up in the cytosol where they are detected by cytosolic nucleic acid sensors such as cGAS, resulting in the induction of inflammatory signaling pathways and an anti-tumor immune response. This suggests that the mode of action of DDR inhibitors may involve the tumor microenvironment (TME). We therefore aimed to assess the influence of combined pharmacological ATR and ATM inhibition on the TME to better understand how this could be exploited therapeutically. In line with published results in human tumor models, the treatment of murine colon cancer MC-38 cells in vitro with a combination of ATR inhibitor tuvusertib and ATM inhibitor lartesertib led to cell death. Further analysis revealed an activation of the cGAS-STING signaling pathway, an upregulation of PD-L1 and the release of inflammatory cytokines. These results confirmed the activation of immune signaling pathways upon combined inhibition of ATR and ATM. To analyze the stimulation of an anti-tumor immune response upon tuvusertib + lartesertib treatment in vivo, MC-38 cells were transplanted into immunocompetent C57BL/6J mice. Immunoprofiling by flow cytometry and immunohistochemistry staining confirmed that treatment with tuvusertib + lartesertib indeed altered the TME in this setting. In line with the in vitro findings, a significant upregulation of PD-L1 on immune and tumor cells could be observed after 24, 48, and 72 h of treatment even though MC-38 cells expressed high levels of PD-L1 already. Immunoprofiling did not reveal any changes in the TME immune cell content at these early time points. Interestingly, PD-L1 expression as well as tumor immune population changed after prolonged (23 days) treatment. PD-L1 was still expressed on tumor cells but to a significantly lesser extent and a depletion of CD8+ T-cells was observed. However, a significant increase in NK cells could be detected. In summary, we show that inhibition of the DDR through a combination of ATR and ATM inhibitors influences the TME in the MC-38 tumor model. These findings suggest an additional mode of action beyond direct cancer cell cytotoxicity. Further studies on how this may be leveraged therapeutically, for example through a combination with immune checkpoint inhibitors, are warranted. 1. Turchick A, Zimmermann A, et al. Mol Cancer Ther 2023;22(7):859-872. Citation Format: Karin Laaber, Audrey Turchick, Julia Jabs, Brian Elenbaas, Lyubomir T. Vassilev, Astrid Zimmermann. Combined inhibition of ATR and ATM with tuvusertib and lartesertib (M4076) impacts the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5617.

Systemic evaluation of novel acaricide hexythiazox for bioactivity improvement and risk reduction at the enantiomer level

Traditional risk assessments of chiral pesticides mainly depend on racemic form, which is often incomprehensive. This study conducted systemic investigations on the bioactivity, toxicity, and ecotoxicological effects of hexythiazox (HTZ) at the enantiomer level. The elution order and absolute configuration of HTZ enantiomers were determined. (4R, 5R)-(+)-HTZ exhibited 708 and 1719 times higher bioactivity against Tetranychus cinnabarinus and Tetranychus urticae eggs than (4S, 5S)-(−)-HTZ, respectively. Molecular docking indicated greater interactions between (4R, 5R)-(+)-HTZ and chitin synthase leading to higher bioactivity of (4R, 5R)-(+)-HTZ. However, (4S, 5S)-(−)-HTZ induced greater changes in protein and malondialdehyde content, and antioxidant and detoxification enzyme activities than (4R, 5R)-(+)-HTZ in earthworms. Furthermore, integrated biomarker response results indicated (4S, 5S)-(−)-HTZ exhibited higher toxic effects on earthworms than (4R, 5R)-(+)-HTZ. Finally, significant differentially expressed genes (DEGs) were observed in earthworms after exposure to (4R, 5R)-(+)-HTZ and (4S, 5S)-(−)-HTZ, respectively. These DEGs were mainly enriched in glycolysis/gluconeogenesis and purine metabolism pathways in earthworms. Additionally, six metabolism pathways were also enriched, including pyruvate metabolism, fatty acid biosynthesis, oxidative phosphorylation, citric acid cycle, fatty acid degradation, and ATP-binding cassette transporters. These findings suggest that earthworms exhibited enantiomer-specific responses to (4R, 5R)-(+)-HTZ and (4S, 5S)-(−)-HTZ. This study provides systemic insight into the toxicity mechanism of HTZ at the enantiomer level and the potential to develop (4R, 5R)-(+)-HTZ as a high-efficiency and low-risk pesticide.

Migration characteristics of constant elements in the process of coal dissolution by liquid CO2

The effect of liquid CO2 on coal dissolution plays a key role in improving coal bed methane (CBM) recovery and CO2 geological storage. In order to study the effect of liquid CO2–H2O reaction on the migration of mineral constant elements in coal, three kinds of coal samples (lignite, bituminous coal, and anthracite) with different degrees of metamorphism were selected as the research objects. The one-factor experiments of dissolution of liquid CO2 and water-bearing coal samples were carried out by simulating the temperature and pressure of the stratum. X-ray fluorescence spectroscopy (XRF) was used to test the changes in the relative content of constant elements in coal samples after liquid CO2 injection under different pressure conditions. Scanning electron microscopy (SEM) was utilized to observe the evolution pattern of the surface features of the coal before and after the dissolution of liquid CO2. A quantitative analysis of coal pore development characteristics was conducted based on low-temperature N2 adsorption/desorption experiments, and isothermal adsorption experiments were carried out before and after etching the coal samples to understand the adsorption characteristics of CH4 and CO2 by coal under different pressure conditions. The research results indicated that the migration ability of constant elements in coal showed a trend of first decreasing and then increasing with the increasing degree of coal metamorphism. Among the three selected coal samples, the migration ability of constant elements was found to be strongest in anthracite, followed by lignite and bituminous coal. Most of the element migration in coal was carried out through chemical reactions (hydrolysis, carbonation, redox), while some elements were primarily transported through physical means (such as the low-temperature impact of liquid CO2). The dissolution process expands the original pore space of coal and generates new pores, greatly increasing the coal's capacity for CO2 adsorption. These findings deepen our understanding of mineral dissolution in coal by liquid CO2 and provide important insights for achieving efficient and long-term coalbed CO2 geological storage and enhanced methane recovery techniques.

A method for amending loose smokeless tobacco with menthol for administration in clinical studies.

Menthol has long been incorporated as a flavor additive in tobacco products and can impact use behaviors. Despite its inclusion in some of the most popular flavored smokeless tobacco (ST) products (e.g., "mint" flavored products), few studies have systematically investigated the impact of menthol on ST use behaviors in prospective empirical studies. Rigorous investigation of ST menthol content on behavioral and physiological outcomes requires ST products with stable and precise levels of menthol; however, commercial product composition variability prevents product comparisons when evaluating the effects of systematic changes in menthol content on clinical outcomes. We developed amended loose moist snuff ST products by treating commercially available, unflavored loose ST with an ethanol-based menthol spiking solution or a nonmentholated ethanol control solution to develop test products with different levels of menthol: 0, 1, 3, and 5mg menthol/g tobacco. We evaluated the stability of menthol content in these products over 24 months and evaluated menthol exposure associated with the products through pharmacokinetic analysis of plasma menthol-glucuronide in human participants (n=22). Menthol content of the amended products was on target, homogenous, and stable for up to 24 months. Menthol exposure (menthol-glucuronide Cmax and AUC) significantly differed between each test product. These data suggest that stable products with nonoverlapping menthol content can be developed using a menthol spiking solution and can be subsequently administered for clinical assessments of mentholated loose ST. The results from this study suggest that a menthol spiking solution can be used to mentholate unflavored, loose ST to a target menthol content. With this method, the ST menthol content was stable for at least 24 months, and the products exposed users to menthol in a dose-dependent manner. This method yielded loose ST products with precise, stable levels of menthol to allow systematic evaluation of ST menthol content on clinical outcomes. The method may have applications for systematically evaluating changes in other tobacco product ingredients.